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Imaging and
Intervention in Urinary
Tract Infections and
Urosepsis
Editor
Massimo Tonolini
Department of Radiology
Luigi Sacco Hospital
Milan, Italy
1 Introduction������������������������������������������������������������������������������������ 3
Massimo Tonolini
2 Introduction to Urinary Tract Infections: An Overview on
Epidemiology, Risk Factors, Microbiology and
Treatment Options ������������������������������������������������������������������������ 7
Maria Diletta Pezzani and Spinello Antinori
3 Uncomplicated and Complicated Urinary Tract Infections
in Adults: The Infectious Diseases’s Specialist Perspective ������ 17
Spinello Antinori and Maria Diletta Pezzani
4 Perspective from the Urologist������������������������������������������������������ 35
Ai Ling Loredana Romanò and Antonio M. Granata
5 Perspective from the Andrologist ������������������������������������������������ 41
Antonio Maria Granata and Ai Ling Loredana Romanò
6 Nothing Is Simple in Acute Pyelonephritis: A Pragmatic,
Semantic Nephrologist’s View������������������������������������������������������ 45
Giorgina Barbara Piccoli and Francesca Ragni
v
vi Contents
Arguably representing one of the most prevailing (d) Systemic inflammatory response syndrome
infectious illnesses worldwide, urinary tract with fever or hypothermia, hyperleucocytosis
infections (UTIs) are generally considered trivial or leucopenia, tachycardia and tachypnoea
by most physicians, since the majority of cases (e) Circulatory and organ failure [2]
encountered in the general population are uncom-
plicated occurrences in otherwise healthy young Furthermore, UTIs represent the commonest
women. However, UTIs account for hundreds of (almost 40%) form of hospital-acquired infec-
thousands of outpatient visits and emergency and tions, with bladder catheterisation as the key risk
hospital admissions yearly, resulting in a signifi- factor. The EAU guidelines define complicated
cant clinical and economic burden [1–3]. UTIs (C-UTIs) as those associated with struc-
Indeed, UTIs encompass a heterogeneous tural or functional abnormalities of the genitouri-
spectrum of conditions ranging from asymptom- nary tract, or with the presence of an underlying
atic bacteriuria to mild uncomplicated cystitis, disease that interferes with host defence mecha-
potentially severe pyelonephritis and life- nisms, that result in an increased risk of acquiring
threatening sepsis. Clinical manifestations of infection or failing therapy. The commonest con-
UTIs may be limited or overlap with pre-existing ditions predisposing patients to either acquiring
complaints from chronic urinary tract dysfunc- infection or experiencing a more severe outcome
tion. According to the European Association of are categorized with the mnemonic RENUC and
Urology (EAU) guidelines, severity of UTIs summarized in Table 1.1 [2].
should be graded clinically as: Traditionally, the vast majority of ascending
UTIs were considered uncomplicated and did not
(a) Asymptomatic routinely require imaging investigation, particu-
(b) Causing local symptoms such as dysuria, uri- larly in women of childbearing age. During my
nary frequency, urgency, supra- or retropubic years as a resident in diagnostic imaging at the
pain or bladder tenderness San Paolo Hospital in Milan (Italy) in the late
(c) Causing general symptoms including fever, 1990s, radiologists were only occasionally
flank pain, nausea and vomiting requested to investigate patients with suspected
UTIs, in the vast majority of cases to exclude uri-
nary obstruction with ultrasound and occasion-
M. Tonolini ally to study sequelae after acute pyelonephritis
Radiology Department, “Luigi Sacco” University (APN) with intravenous pyelography. In fact,
Hospital, Via G.B. Grassi 74, Milan 20157, Italy until a few years ago, the diagnosis of UTI was
e-mail: mtonolini@sirm.org
Table 1.1 Risk factors for acquiring urinary tract infection, developing complications and/or failing treatment (mne-
monic RENUC) (Reproduced from Open Access Ref. no.[17], partially adapted from Ref.no. [2])
Type Risk factors Risk of more severe outcome
Recurrent Sexual behaviour No
Contraceptive devices
Postmenopausal hormonal deficiency
Controlled diabetes mellitus
Extra-urogenital Pregnancy Yes
Male gender
Badly controlled diabetes
Immunosuppression including HIV, uraemia,
transplant recipients, on corticosteroids,
chemotherapy or immunosuppressants
Connective tissue disease
Nephropathy Impaired renal function Yes
Polycystic kidney
Urological Obstructive uropathy, e.g. congenital, Yes
lithiasis, stricture, tumour
Short-term catheterisation
Neurogenic bladder
Urological surgery or instrumentation
Permanent catheter or non- Long-term catheter Yes
resolvable urological risk factors Non-resolvable obstruction
Badly controlled neurogenic bladder
primarily clinical and based upon a combination tions and on the increasingly concerning issue of
of clinical symptoms and signs plus consistent bacterial resistance to antibiotics.
urinalysis and biochemical changes. At those Furthermore, growing evidence has accumu-
days, imaging was reserved for: lated on the potential detrimental effect of UTI on
renal function, which results from a combination
(a) Patients with unusually severe symptoms, in of direct cellular injury and indirect effects of
which differentiation from renal colic or inflammatory mediators. In patients with pre-
other acute abdominal disorders was required existing normal renal anatomy and function, renal
(b) Patients with recurrent UTIs, to look for
scarring has been reported to develop in up to
underlying treatable structural or functional 55% of patients after APN. Patients with chronic
abnormalities kidney disease or diabetes are particularly prone
(c) Patients with predisposing conditions to to progression of renal infection and deterioration
C-UTIs such as diabetes, immunosuppres- of function, with the latter becoming permanent
sion, etc. in the majority (77%) of cases [2, 7].
(d) Patients who failed to respond to conven- A highly prevalent disease, APN, reaches an
tional antibiotic therapy within 72 h [4–6] annual incidence of 250,000 cases and yearly
accounts for over 100,000 hospitalizations in the
Meanwhile, during the last decade, the scenario USA, with a non-negligible mean duration
of UTI has changed, as discussed in the first sec- (11 days). However, there is no consensus on the
tion of this book which includes current clinical definition of APN, which – until a few years ago –
perspectives from prominent urologists, nephrolo- was almost invariably diagnosed clinically on the
gists and specialists in infectious diseases. In these basis of fever, flank pain and tenderness, signs and
chapters emphasis is placed on high-risk popula- symptoms of lower UTI, accompanied by leucocy-
1 Introduction 5
tosis, increased acute phase reactants, haematuria, a consistent basis for correct therapeutic choice.
bacteriuria and positive urine culture [2]. Emphasis is placed on the increasingly imple-
However, several recent studies-particularly mented diffusion-weighted (DW)-MRI sequences
those by G.B. Piccoli and C. Rollino-reported and apparent diffusion coefficient (ADC) maps
that APN presents with full-blown features in to differentiate between spared parenchyma,
only a minority of patients. The correlation nephritis and abscesses, particularly in children
between clinical presentation, entity of abnormal and patients with contraindication to intravenous
biochemistry (C-reactive protein and leukocyte contrast [12–16].
count) and extent of renal lesion in APN is often The third section of this volume reviews the
very limited: oligosymptomatic manifestations imaging appearances of UTIs involving the pros-
may correspond to multifocal lesion or abscesses, tate, seminal vesicles, urethra, perineum, penis
which require hospitalization and long-term ther- and scrotum. Despite improved standards of
apy, and are associated with higher risk of devel- care, “lower” UTIs are increasingly observed in
oping renal scarring. Furthermore urine, blood patients with risk factors such as neurogenic dys-
cultures and both are positive only in 23.5–40%, function, bladder outlet obstruction, obstructive
15.8–30% and 7.6% of cases, respectively, uropathy, urologic instrumentation or indwelling
mostly because of previous empirical antibiotic stent, urinary tract postsurgical modifications,
therapies administered in the outpatient setting chemotherapy or irradiation, renal dysfunction,
[8–10]. Conversely, a few other studies showed diabetes and immunodeficiency [3]. With ade-
that some early available clinical predictors, quate technique and awareness of consistent find-
namely, diabetes, hypotension, high leucocytosis ings, CT and MRI comprehensively assess the
and acute renal failure, may identify almost all lower genitourinary structures and disorders and
patients with moderate (except for some cases of increasingly provide accurate detection of pres-
microabscesses) and severe APN [11]. ence and extent of infectious changes, of pos-
Since choosing the most appropriate treatment sible complications, and assist in the differential
relies on severity assessment, nowadays there is a diagnosis [17].
growing need for “pathological” diagnosis of Furthermore, in our experience imaging signs
APN by radiological demonstration of parenchy- of clinically unsuspected C-UTI may be inci-
mal involvement; this is particularly true for dentally detected in imaging studies performed
abscessual forms, which require longer intensive to investigate other conditions such as urolithia-
in-hospital intravenous antibiotic therapy and are sis, renal colic, gynaecologic pain or unspecific
associated with higher risk of developing renal abdominal pain [17]. Cross-sectional imaging is
scars [2]. paramount in the triage of sepsis, to confirm an
Meanwhile, state-of-the-art multidetector underlying urological cause: albeit less severe
computed tomography (CT) and magnetic reso- compared to other sources, urosepsis remains
nance imaging (MRI) reached extremely high associated with 20–40% mortality [2, 7].
accuracy in delineating the nature and extent of Other dedicated chapters, respectively, review:
APN changes and consistently depict complica-
tions such as abscess and obstruction. Emergency –– The role of nuclear medicine (specifically
physicians increasingly request early imaging of with positron emission tomography) in the
suspected APN, which is preferably carried out detection and follow-up of infections in poly-
with MRI particularly in young patients and cystic kidneys
childbearing age women. Therefore, the fol- –– The imaging of urogenital tuberculosis in the
lowing ample radiological section of this book current CT era
reviews the role, techniques and imaging appear- –– The imaging of UTI in patients with renal
ances of upper UTIs using ultrasound and con- transplant
trast-enhanced ultrasound (CEUS), multidetector –– The expanding role and possibilities of inter-
CT and MRI to assess severity and thus provide ventional radiology in the treatment of severe
6 M. Tonolini
urinary tract infections including drainage of 5. Stunell H, Buckley O, Feeney J et al (2007) Imaging
of acute pyelonephritis in the adult. Eur Radiol
infected urine and percutaneous treatment of
17:1820–1828
abscesses collections 6. Craig WD, Wagner BJ, Travis MD (2008)
Pyelonephritis: radiologic-pathologic review.
Finally, a specific chapter summarizes the cur- Radiographics 28:255–277. quiz 327-258
7. Sorensen SM, Schonheyder HC, Nielsen H (2013)
rent status of paediatric UTI imaging including
The role of imaging of the urinary tract in patients
anatomic, functional and reflux studies, borrow- with urosepsis. Int J Infect Dis 17:e299–e303
ing from experience at hospitals especially 8. Rollino C, Beltrame G, Ferro M et al (2012) Acute
devoted to children care. pyelonephritis in adults: a case series of 223 patients.
Nephrol Dial Transplant 27:3488–3493
As Editor, I hope that the effort made by all
9. Abraham G, Reddy YN, George G (2012) Diagnosis
contributors will be effective in producing an up- of acute pyelonephritis with recent trends in manage-
to-date volume which will prove useful to prac- ment. Nephrol Dial Transplant 27:3391–3394
ticing clinicians and radiologists who are daily 10. Piccoli GB, Consiglio V, Deagostini MC et al (2011)
The clinical and imaging presentation of acute “non
confronted with potentially severe UTIs. Our aim
complicated” pyelonephritis: a new profile for an
is to increase familiarity with these disorders ancient disease. BMC Nephrol 12:68
which frequently require in-hospital manage- 11. Lim SK, Ng FC (2011) Acute pyelonephritis and
ment, sometimes including intensive care admis- renal abscesses in adults - correlating clinical param-
eters with radiological (computer tomography) sever-
sion, percutaneous interventions or even surgery,
ity. Ann Acad Med Singap 40:407–413
in order to decrease the associated morbidity. 12. Martina MC, Campanino PP, Caraffo F et al (2010)
Dynamic magnetic resonance imaging in acute pyelo-
nephritis. Radiol Med 115:287–300
13. De Pascale A, Piccoli GB, Priola SM et al (2013)
Diffusion-weighted magnetic resonance imaging: new
References perspectives in the diagnostic pathway of non-complicated
acute pyelonephritis. Eur Radiol 23:3077–3086
1. Cardwell SM, Crandon JL, Nicolau DP et al (1995) 14. Faletti R, Cassinis MC, Fonio P et al (2013) Diffusion-
Epidemiology and economics of adult patients hos- weighted imaging and apparent diffusion coefficient
pitalized with urinary tract infections. Hosp Pract values versus contrast-enhanced MR imaging in the
44:33–40 identification and characterisation of acute pyelone-
2. Grabe M, Bartoletti R, Bjerklund-Johansen TE et al phritis. Eur Radiol 23:3501–3508
(2014) Guidelines on urological infections. European 15. Vivier PH, Sallem A, Beurdeley M et al (2014)
Association of Urology Available at: http://uroweb. MRI and suspected acute pyelonephritis in children:
org/wp-content/uploads/19-Urological-infections_ comparison of diffusion-weighted imaging with
LR2.pdf gadolinium- enhanced T1-weighted imaging. Eur
3. Roghmann F, Ghani KR, Kowalczyk KJ et al (2013) Radiol 24:19–25
Incidence and treatment patterns in males pre- 16. Rathod SB, Kumbhar SS, Nanivadekar A et al (2015)
senting with lower urinary tract symptoms to the Role of diffusion-weighted MRI in acute pyelone-
emergency department in the United States. J Urol phritis: a prospective study. Acta Radiol 56:244–249
190:1798–1804 17. Tonolini M, Ippolito S (2016) Cross-sectional imag-
4. Browne RF, Zwirewich C, Torreggiani WC (2004) ing of complicated urinary infections affecting the
Imaging of urinary tract infection in the adult. Eur lower tract and male genital organs. Insights Imaging
Radiol 14(Suppl 3):E168–E183 7(5):689–711
Introduction to Urinary Tract
Infections: An Overview on 2
Epidemiology, Risk Factors,
Microbiology and Treatment
Options
Maria Diletta Pezzani and Spinello Antinori
UTIs have a tendency to recur. A recurrence is evaluating the impact of six healthcare-associated
defined as three symptomatic UTIs within infections in Europe estimated an occurrence of
12 months or two symptomatic episodes half a 2,609,911 new cases of HAIs every year in the
year following clinical resolution of a previous European Union and European Economic Area
UTI, and it implies a period of time without bac- (EU/EEA). Hospital-acquired UTIs (HA-UTIs)
teriuria or signs of infection [3]. Clinically a represented almost 30% of the total burden, espe-
recurrence occurring within 2 weeks from a pre- cially among hospitalized 65-year-old patients
vious episode is classified as a relapse otherwise and above, with 777,639 cases yearly and an inci-
is considered a reinfection. The majority of recur- dence of 152/100,000 population [12].
rences are thought to be reinfections [4]. Repeated Except for infants and elderly, females are
ascending infection and chronic infection in the more likely to experience UTIs than males. In
bladder seem to be the two mechanisms causing childhood, especially during the first year of life,
recurrences. This is supported by recent discov- the incidence of UTIs among uncircumcised
eries in the pathogenesis of UTIs leading to new boys is 20.3% against a 5% in girls [13, 14]. This
insights about the persistence of bacteria and trend is going to reverse in the prepubertal age
their ability to survive in the bladder [5]. when about 3% of girls are diagnosed with UTIs
versus 1% of boys [13]. It is estimated that
among young, healthy women around 50–60%
2.2 Epidemiology of them will experience at least one UTI in their
lifetime [15].A surveillance study based on self-
UTIs are one of the most common bacterial infec- reported questionnaire found out an annual inci-
tions seen in both hospital and outpatient set- dence of UTIs of 12%, and by the age of 32, half
tings. In the United States in 2010, the emergency of all women report having had at least one UTI
department (ED) visits with a primary diagnosis [16]. Women are also more susceptible to recur-
of UTI were more than 3 million: Of these 84.5% rences [17]. A study conducted among college
were women and among them approximately women who had already experienced one UTI
half of all UTIs presentations between 18 and 40 showed that 27% experienced a recurrence
of age [6]. In 2012 UTIs accounted for 25.3% of within 6 months after the first episode, and 2.7%
all ID-related ED visits of elderly adults in the had a second recurrence over the same time of
United States with a hospitalization rate of 17% period [3, 18]. Incidence of UTIs in men
[7]. It is difficult to estimate the real incidence of increases after the age of 60. This is essentially
UTIs in the outpatient setting as studies differ for due to the physiologic changes that occur in the
the case selection criteria, source of data and structure and function of urinary tract which
sample size. A Swiss study found an incidence impair normal voiding with benign prostatic
rate of visits to a GP for lower UTIs at 1.6 per hyperplasia as the most common cause of
100 inhabitants per year [8]. In Canada incidence obstruction of urine flow [19]. The trend in the
rates of UTIs with positive cultures have been incidence of UTIs is similar among both genders
estimated at 17.5 per 1000 inhabitants per year in the eight decade of life [20].
[9]. In France the annual incidence rate of con- Symptomatic UTI is the second most common
firmed UTIs in general practice was estimated at infection in residents of long-term care facilities
2400 per 100,000 women [10]. (LTCF) with an estimated incidence rate of 0.1–
UTIs represent also an important burden 2.4 per 1000 resident-day [21]. Indwelling urinary
among healthcare-associated infections (HAIs). catheters contribute to the burden of UTIs giving a
A prevalence survey conducted in the United daily risk of acquiring bacteriuria of 3–7% [22].
States estimated that there were 648,000 patients The extensive use of indwelling catheters, 17.5%
with 721,8000 HAIs in acute care hospitals in in 66 European Hospitals and 23.6% among 183
2011. Among these, 93,3000 were UTIs and US hospitals [11], is responsible of a four- to six-
35,600 CA-UTIs [11]. Another recent study fold increase of having a symptomatic urinary
2 An Overview on Epidemiology, Risk Factors, Microbiology and Treatment Options 9
tract infection with consequent excessive antimi- study examining the 1-year prevalence and health-
crobial use and risk of adverse outcomes [23]. care costs implications of UTIs in a type 2 diabe-
tes population in the United States observed an
8.2% risk of one or more UTIs diagnoses during a
2.3 Risk Factors 1-year study period [32]. Prevalence of AB in
women with DM is three to four times greater
Many classifications have been proposed to assess than in woman without DM as the frequency of
factors which expose the individual at risk for symptomatic infection [33]. In particular, in a
UTI. Genetic predisposition, behavioural factors, cohort of women with DM type 2, ABU was the
host factors and risk for UTIs results from a complex most important risk factor for developing symp-
interaction between all of these elements [1, 24, 25]. tomatic UTI (34% in women with ABU vs. 19%
The higher susceptibility of female sex is in those without). Higher glucose urine concen-
firstly due to anatomical characteristics with the tration, decrease immune function, duration and
proximity of the female urethra to the vaginal severity of diabetes and possible autonomic neu-
cavity and to the rectum. This increases the prob- ropathy leading to urinary retention are all factors
ability of colonization of the periurethral mucosa identified as possible responsible for increased
by potential uropathogens and thus facilitating susceptibility [31]. Surprisingly, HbA1c, which
the ascending route of infection to the bladder or expresses the degree of glycaemia, does not seem
the kidney. Specific behaviours have been associ- to correlate with UTIs risk [31]. Despite bacterial
ated to UTIs. Studies among college women have aetiology is qualitatively the same, patients with
shown that sexual intercourse, use of spermicides type 2 diabetes are more likely to be infected with
and diaphragms and number of sexual partners uropathogen-resistant strains and to be exposed to
increase risk of acquiring UTIs [26, 27]. serious complications of UTIs such as emphyse-
A prior UTI is a well-known risk factor for matous conditions of the bladder and the kidney,
further episodes. It is estimated that among renal abscesses and papillary necrosis [29].
young, healthy women, around 20–30% with a There is a growing evidence about the correla-
first UTI will experience two or more episodes, tion between obesity and the risk of infection (i.e.,
and around 5% will have recurrences. These high blood stream infection, ventilator- associated
rates of recurrences were observed in studies pneumonia, influenza infection, etc.), and in the
conducted in different time, but they all con- last years, a few studies have specifically evalu-
firmed these frequencies [3, 25]. In postmeno- ated obesity as a possible additional risk factor for
pausal women, further predisposing factors are UTIs. It has come out that obese people have a
advancing age, comorbidities and urological fivefold increase of risk of developing pyelone-
abnormalities favouring incontinence; the role of phritis compared to those nonobese [34]. For
oestrogens, which are believed to contribute to males with a BMI of 50 kg/m2 or more, there is an
UTIs, is controversial [28]. increased risk of 2.38 and for females 1.25 [35].
Type 2 diabetes mellitus (DM2) has always Recently, a study conducted in Israel among 122
been considered a predisposing factor for infec- premenopausal women have shown an overall
tions and most commonly UTIs [29]. Incidence of prevalence of recurrent UTI (RUTI) of 23.4 and
diabetes is increasing: in the United States, there 49.5% of those were obese. The study took into
were 1.7 million new diabetes cases among adults account also age, the use of contraceptive, sexual
aged 20 years or older in 2012, and in the period intercourse, diabetes mellitus and metabolic syn-
2009–2012, at least 37% of adults aged 20 years drome, but there was no statistical difference
or older had prediabetes (altered fasting glucose between cases and controls except, interestingly,
or A1C levels) [30]. Previous epidemiological for maternal history of RUTI, use of probiotics
studies have shown a 1.2–2.2 increase in the rela- and BMI [36]. It is presumable that, similar to dia-
tive risk of UTI in patients with diabetes com- betes even with different mechanisms, dysregula-
pared with those without [31]. Moreover, a recent tion of the immune system caused by altered
10 M.D. Pezzani and S. Antinori
Table 2.2 Characteristics of antimicrobial agents used for UTIs and mechanisms of resistance [47–49]
Antibiotic Mechanism of action Type of activity Bacterial resistance mechanism
Βeta-lactams Inhibit bacteria cell Bactericidal Hydrolysis by β-lactamase
wall biosynthesis Mutation of the target site (penicillin-binding
protein)
Aminoglycosides Inhibit protein Bactericidal Inactivation through acetylation, nucleotidylation
synthesis by bacteria or phosphorylation
Target site mutation (methylation of 16S rRNA)
Sulphonamides Interfere with Bacteriostatic Overproduction of dihydropteroic acid synthase
bacterial growth and (DHPS) or dihydrofolate reductase (DHFR)
multiplication Altered DHPS—essential for folate synthesis in
bacteria—leads to sulphonamide resistance and
altered DHFR with loss of inhibition by
trimethoprim
Quinolones Interfere with bacteria Bactericidal DNA gyrase mutations
DNA replication and Protein binding of quinolone active
transcription
Polymyxin Disrupt the structure Bactericidal Mutation in lipopolysaccharide
of the bacterial cell
membrane
States showed that among 291 patients infected or contrast, only dysuria can be present at the onset
colonized with ESBL-producing E. coli as outpa- of the infection, so they need to be correlated
tients or within 48 h of hospitalization, 107 with patient’s clinical history (age, gender, pres-
(36.8%) had community-associated infection of ence of risk factors for UTIs). In women the dif-
which 81.5% were urinary tract infection [49]. ferential diagnosis includes sexually transmitted
Recognized risk factors for community-onset diseases (STD) such as urethritis and vaginitis
ESBL infections are recurrent UTIs coupled with although they are usually accompanied by vagi-
underlying renal pathology, recent exposure to nal irritation or discharge [53]. A meta-analysis
fluoroquinolones, previous hospitalization, of studies of uncomplicated UTIs in women esti-
advanced age, diabetes mellitus and underlying mated that the probability of cystitis is greater
liver disease. In the hospital setting, ESBL infec- than 50% in women with any symptoms of uri-
tions were significantly linked to intensive care nary tract infection and greater than 90% in
unit stay, prolonged ‘time at risk’ (i.e., time from women who have dysuria and frequency without
admission to culture), presence of foreign medical vaginal discharge or irritation [54]. In men, bac-
devices (i.e., central lines, nasogastric tube, uri- terial prostatitis manifests with lower UTI symp-
nary catheter and endotracheal tube), mechanical toms plus fever and obstructive symptoms due to
ventilation, recent prior invasive procedures and prostate inflammation such as hesitancy, noctu-
recent administration of antimicrobials (especially ria, slow stream and dribbling [19]. Suspicion of
third-generation cephalosporins) [52]. pyelonephritis rises in the presence of systemic
symptoms such as temperature >38 °C, chills,
nausea or vomiting together with flank pain or
2.5 Diagnosis costovertebral angle tenderness with or without
cystitis symptoms. Complicated pyelonephritis
Diagnosis of UTI syndromes relies on clinical may also present with sepsis or multiorgan sys-
evaluation supported by laboratory findings. tem dysfunction [4]. The elderly might have an
Symptoms like dysuria, frequency, urgency, atypical presentation with nonspecific symptoms
suprapubic pain and haematuria are highly sug- as fever or altered mental status [53].
gestive for lower UTI. However these manifesta- Dipstick test and urine culture are the most
tions do not occur necessarily all together or, by supporting tests for the diagnosis of UTIs. The
12 M.D. Pezzani and S. Antinori
first one tests for leukocyte esterase, an enzyme tal, fosfomycin trometamol and pivmecillinam.
present in host’s urine polymorphonuclear leuko- Trimethoprim–sulphamethoxazole remains
cytes, and nitrites, which derives from the reduc- highly effective only in areas where resistance
tion of nitrate by the Enterobacteriaceae. rates of E. coli are known to be <20%; however,
Leukocyte esterase has a sensitivity of 62–98% it should be avoided if used for UTI in the last
and specificity of 55–96%. Urine nitrite is highly 3 months. Aminopenicillins and oral cephalospo-
specific but has a poor sensitivity [6]. A positive rins, because of minor efficacy as short-course
dipstick test strongly supports the diagnosis of therapy and of resistance patterns, should be con-
UTI in a patient with typical symptoms, but a sidered only when the other recommended drugs
negative one, if the clinical suspicion is high, cannot be used. In the ARESC study, almost 20%
does not rule it out. Urine microscopy reveals of all the 2315 E. coli isolates exhibited low sus-
pyuria, which is present in the majority of patients ceptibility to amoxicillin/clavulanate, cefurox-
with acute cystitis and pyelonephritis [4]. ime and nalidixic acid, while resistance rates for
Noteworthy, in catheterised patients, pyuria is not ciprofloxacin exceeded 10%. In each country fos-
diagnostic of catheter-associated bacteriuria or fomycin, mecillinam and nitrofurantoin were the
symptomatic UTI. Urine culture is the gold stan- most active drugs against E. coli [43]. These data
dard for the diagnosis. Traditionally a bacterial are in line with those from the ECO SENS study
count ≥105 CFU/mL has been considered the which have registered higher resistance level in
threshold predictive of bladder bacteriuria. E. coli for amoxicillin/clavulanate, ciprofloxacin,
However, because 30–50% of women with cysti- ampicillin, TMP–SMX than mecillinam, fosfo-
tis have between 102 and 104 CFU/mL in voided mycin trometamol and nitrofurantoin (<2%) with
urine and the vast majority of patients with pyelo- a rising trend from 1999 to 2008 [56]. For men, a
nephritis have ≥104 CFU/mL uropathogens in longer antibiotic course has always been sug-
urine culture, a quantitative count ≥103 is now gested (7–14 days) due to concerns of persistence
suggested as a reasonable indicator of acute of bacteria in the prostate favouring thus early
uncomplicated cystitis while count ≥104 CFU/ recurrences [57]. Data on the best duration treat-
mL of pyelonephritis [1, 4, 53]. ment are controversial. One observational study
has shown no reduction in early or late UTI
recurrences for treatment duration >7 days [58]
2.6 Treatment contrasting with a clinical trial comparing 3 days
vs. 14 days of ciprofloxacin which have under-
Screening and treatment of asymptomatic bacte- lined a clear benefit [59]. However, the first study
riuria are generally not recommended except for: was conducted among male veterans in an outpa-
tient setting and the second one in spinal cord
–– Pregnant women, who are at major risk for injury patients, a special subpopulation at risk so
symptomatic UTIs and pyelonephritis it is difficult to compare the results. Noteworthy,
(between 15–45%) if not treated [55] a long-duration therapy has to be balanced with
–– Those subjecting to urological procedures, the risk of Clostridium difficile infection [58]. In
who are at risk for complicated infections [1] accordance to susceptibility testing and to local
resistance patterns, TMP–SMX and quinolones,
The choice of the treatment should be guided because of their better penetration in the prostatic
by the antibiogram, and it should include same tissue, should be preferred in men.
antibiotics recommended for uncomplicated or For acute uncomplicated pyelonephritis not
complicated UTIs considering host risk factors requiring hospitalization, 7 days of a fluoroquino-
and comorbidities. lone (in area with resistance <10%) or 14 days of
Guidelines [1, 2] recommend the following TMP–SMX are the first-line choices. Quinolones
agents as first choice for the treatment of lower have a broad spectrum of activity against many
uncomplicated UTIs: nitrofurantoin macrocrys- gram-negative bacteria so they have become a
2 An Overview on Epidemiology, Risk Factors, Microbiology and Treatment Options 13
first-line choice for UTIs. However increasing apy for the treatment of outpatient ESBL UTIs
resistance rates, from 1–4% to 6–15%, have been has shown noninferiority of fosfomycin with sim-
demonstrated, and even if in the community resis- ilar results between the two groups [63].
tance remains <20%, MDR bacteria have dis- Nitrofurantoin exhibited a consistent antimicro-
played rates of resistance between 49 and 72% bial activity against outpatient MDR E. coli iso-
[60]. Surveillance data on TMP–SMX have esti- lated between 2001 and 2010 in the United States.
mated resistance rates ranging from 16% to 36% Despite a decrease in the pan-susceptibility from
globally and between 60 and 77% among MDR 52.1% in 2001 to 42% in 2010, resistance to nitro-
[60]. For these reasons, these two agents should be furantoin was found only in 2.1% in 2010 [64].
considered carefully, and initiation with a paren- Another study evaluating the efficacy in vitro of
teral antimicrobial such as ceftriaxone or an ami- five oral agents (including fosfomycin, nitrofu-
noglycoside may be warranted [2]. In case of rantoin, sulfamethoxazole–trimethoprim, cipro-
pyelonephritis requiring hospitalization, suggested floxacin and ampicillin) on 91 MDR uropathogens
antimicrobials for intravenous therapy are amino- has found that fosfomycin and nitrofurantoin
glycosides, extended-spectrum cephalosporins, were the most active drugs with 96.7 and 76.7%
beta-lactams in combination with beta-lactams of susceptibility against ESBLs producers, respec-
inhibitors and carbapenems. The choice between tively [65]. The limit of fosfomycin and nitrofu-
these drugs has to take into account local resis- rantoin is their lack of tissue penetration so for
tance patterns and susceptibility testing [1, 2]. UTIs due to MDR bacteria carbapenems and
Treatment of CA-UTIs has to be considered combination therapies with carbapenems, amino-
only for those with appropriate signs and symp- glycosides and polymyxins are preferable [66].
toms attributable to the urinary tract and after the The role of BLBLI is controversial. Piperacillin–
exclusion of other sources of infection. In fact tazobactam can be a carbapenem-sparing option
pyuria in patients with indwelling urinary cathe- against susceptible ESBL producers and for less
ters can be present with or without bacteriuria as serious infections [67]. However, new combina-
a result of bladder inflammation, so it is not an tions have become available. Ceftolozane–tazo-
indication whether to start antimicrobial therapy. bactam and ceftazidime–avibactam have been
If the catheter has been in place for more than recently approved for the treatment of compli-
7 days, it should be removed before the initiation cated UTIs. Ceftolozane is a novel cephalosporin
of an antibiotic. Duration of treatment can vary with enhanced activity against gram-negative
between 7 and 14 days according to the severity pathogens including P. aeruginosa and
of the clinical presentation [1, 2]. Enterobacteriaceae. The addition of tazobactam
Treatments for multidrug-resistant uropatho- confers activity against class A and C ESBLs
gens rely on drugs which still retain antimicrobial Enterobacteriaceae but not towards metallo-β-
activity and on a few new available options. A ret- lactamases, K. pneumonia carbapenemases or
rospective analysis on the use of oral fosfomycin others. The spectrum of activity of ceftolozane–
for the treatment of MDR UTIs has shown a treat- tazobactam includes also streptococcal species
ment success rate, defined by neither persistence and Bacteroides fragilis, but it has limited cover-
nor recurrence by the same organism, of 55% age against Staphylococcus spp. and other gram-
[61]. A recent survey on 204 MDR urine isolates negative anaerobes [68]. Avibactam is a novel
has found an overall resistance to fosfomycin of β-lactamase inhibitor which restores the in vitro
21.6 and 19% among the ESBL producers with activity of ceftazidime against Ambler class A,
the lower rate in E. coli than that of Klebsiella class C and some class D β-lactamase producers;
spp. Noteworthy 83.3 and 63.7% of the isolates it is not active against metallo-β-lactamases
were resistant to fluoroquinolones and TMP– (Table 2.3). Noninferiority of ceftazidime–avi-
SMP, respectively [62]. Another retrospective bactam vs. doripenem has been demonstrated in
cohort study performed to compare oral fosfomy- phase III clinical trials [69]. These new combina-
cin to intravenous ertapenem as step-down ther- tions are good carbapenem-sparing options but
14 M.D. Pezzani and S. Antinori
have to be used wisely through the implementa- and chronic urinary tract infection. Infect Immun
79:4250–4259
tion of programmes of antimicrobial stewardship
6. Takhar SS, Moran GJ (2014) Diagnosis and man-
to limit the development of further resistance. agement of urinary tract infection in the emergency
department and outpatient settings. Infect Dis Clin N
Am 28:33–48
7. Goto T, Yoshida K, Tsugawa Y, Camargo CA,
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Uncomplicated and Complicated
Urinary Tract Infections in Adults: 3
The Infectious Diseases’s Specialist
Perspective
Spinello Antinori and Maria Diletta Pezzani
Urinary tract infections (UTIs) are responsible in risk factors that will render the individual more
Western countries of thousands of outpatient vis- prone to develop UTI [8, 9].
its as well as emergency and hospital admissions Although the classification of any disease is
[1, 2]. The clinical syndromes associated with generally far from to be perfect and acceptable by
UTIs may range from asymptomatic bacteriuria everyone involved in their management, we
to the more severe picture of pyelonephritis and believe that the UTI classification developed by
urosepsis sometimes designated (including also the European Association of Urology (EAU) and
prostatitis in men) as “febrile urinary tract the European Section of Infection in Urology
infections” [3, 4]. (ESIU) is currently the best working approach to
However, the concept of uncomplicated and be considered [10, 11].
complicated urinary tract infection (c-UTI) still This classification is organized in five main
remains a matter of concern because severe infec- categories (clinical criteria, possible risk factors,
tions or those with invasive tissue involvement pathogens, mode of acquisition of UTI and thera-
are sometimes erroneously indicated as c-UTI [3, peutic options) (Table 3.1) [11, 12]. The clinical
5, 6]. The concept and the categorization of criteria are arranged by syndromes: urethritis
c-UTI were introduced by a panel of experts of (UR), cystitis (CY), pyelonephritis (PY), urosep-
the Infectious Diseases Society of America sis (US) and male accessory gland infections
(IDSA) in order to make more easy the evalua- (i.e., prostatitis, vesiculitis, epididymitis and
tion of antimicrobial treatment in different set- orchitis). The latter, together with urethritis, is
ting [7]. It should be acknowledged that the term not considered here given the great variability of
“uncomplicated” refers to any infection observed clinical presentation. It should be highlighted
in patients without known structural or functional that asymptomatic bacteriuria is not considered
an infection but rather a risk factor that needs to
S. Antinori (*) be treated only in selected circumstances such as
III Division of Infectious Diseases, Luigi Sacco pregnancy or surgery of the urinary tract.
Hospital, ASST Fatebenefratelli Sacco, Department Considering the three clinical syndromes—CY,
of Biomedical and Clinical Sciences Luigi Sacco,
University of Milano, Via GB Grassi 74, Milan, Italy PY and US—a grading of severity was suggested
e-mail: spinello.antinori@unimi.it; with six items that include at the extremes the
M.D. Pezzani less severe form, cystitis (grade 1), and the more
Department of Biomedical and Clinical Sciences severe form, uroseptic shock (grade 6) (Table 3.2).
Luigi Sacco, University of Milano, Via GB Grassi 74, As far as risk factors, the difficulty to weight all
Milan, Italy
categories in a proper way due to the lack of solid
e-mail: diletta.pezzani@gmail.com
Table 3.1 EAU/ESIU criteria for classification and patient assessment in urinary tract infectiona
IV. Situation-
III. Pathogen/ circumstances
aetiological under which UTI V. Therapeutic
I. Clinical criteria II. Possible risk factors agent was acquired options
1. Clinical presentation 1. Patients characteristics 1. Bacterial load 1. Community 1. Pathogen(s) is
a. Urethritis (UR) a. Gender (male, female) 2. Pathogens 2. Outpatient (are) susceptible
b. Cystitis (CY) b. P rematurity, newborn, (type, species) service against
c. Pyelonephritis (PY) young child, adolescent 3. Antimicrobial a. Hospital setting commonly used
d. Urosepsis (US) c. Premenopause susceptibility/ b. Private practice antimicrobials
e. Male adnexitis (MA)a d. Pregnancy resistance 3. Inpatient service a. Which are
e. Postmenopause 4. Virulence (hospital) available
f. Elderly (geriatric: physically 4. Long-term b. W hich are not
or mentally handicapped) residential easily available
2. Specificity of 2.Relevant disease outside the accommodation, 2. Pathogen(s) has
symptoms urinary tract nursing home (have) limited
a. UTI specific a. Immunosuppression 5. Healthcare susceptibility
i. Lower UTI (CY): i. Innate associated against
dysuria, frequency, ii. Acquired (AIDS) commonly used
urgency, suprapubic b. Diabetes mellitus antimicrobials
pain c. Other disorders a. But alternative
ii. Upper UTI (PY): antimicrobials
fever, flank pain are available
CVA tenderness b. B ut alternative
b. U TI non-specific antimicrobials
symptoms are not easily
i. Catheter-associated available
UTI (bladder spasm, 3. Pathogen(s) is
unexplained fever) (are)
ii. newborn and young multiresistant,
children and appropriate
iii. Elderly patients antimicrobials
(fever, confusion) are not (or not
iv. Patients with easily) available
neurogenic disorders
3. Severity of symptoms 3. Nephrological risk factors—
a. Mild status of the kidneys
b. Moderate a. Impaired kidney function
c. Severe b. Kidney abscess
d. Septic c. Polycystic renal disease
4. Pattern of infection 4. Urological risk factors
a. Isolated or sporadic a.Functional disorders (reflux,
b. Recurrent neurogenic bladder
i. Relapse disturbances)
ii. Reinfection b. O bstruction without
c. Unresolved or chronic infectious nidus (tumour,
noninfected stone)
c. Obstruction with infectious
nidus (stent, necrotizing
tumour, infective stones)
5. External catheter
a. Urethral
b. Suprapubic
c. Nephrostomy
d. Others
6. Asymptomatic bacteriuria
EAU European Association of Urology, ESIU European Society of Infectious Urology, UTI urinary tract infection, CY
cystitis, PY pyelonephritis, CVA costovertebral angle
a
Bjerklund Johansen TE, et al. Critical review of current definitions of urinary tract infections and proposal of an EAU/
ESIU classification system. Int J Antimicrob Agents (2011); 385:64–70
3 Uncomplicated and Complicated Urinary Tract Infections in Adults 19
data has led to the proposal to use a new system 3.1 Asymptomatic Bacteriuria
for phenotyping designated with the acronym
ORENUC (Table 3.3). Asymptomatic bacteriuria is defined as the
In the era of widespread diffusion of absence of urinary symptoms and a positive urine
multidrug-resistant bacteria in some cases with culture (midstream sample of urine with at least
very limited or absent antimicrobial options, it is 105 CFU/mL) with the same bacterial strain in
imperative to recognize and manage UTIs in the two consecutive samples (for women) and in a
appropriate manner. single sample for men [13].
20 S. Antinori and M.D. Pezzani
Table 3.3 Host risk factors categorized according to the ORENUC systema
Type Risk factors Risk of more severe outcome
O No known risk factor (i.e., healthy No
premenopausal women)
Recurrent Sexual behaviour No
Postmenopausal hormone deficiency
Contraceptive devices
Controlled diabetes mellitus
Extra-urogenital Prematurity, newborn Yes
Male gender
Pregnancy
Uncontrolled diabetes mellitus
Relevant immunosuppression
Nephropathy Impaired renal function Yes
Polycystic kidney
Urological Obstructive uropathy (i.e., stone, tumour) Yes
Short-term catheterization
Urological surgery
Catheter Long-term catheter Yes
Non-resolvable urinary obstruction
Neurogenic bladder badly controlled
a
Smelov V et al. Improved classification of urinary tract infection: future consideration. European Urology Supplements
2016;15:71–80
Screening and treatment for asymptom- (O, R and partially E risk factors of the ORENUC
atic bacteriuria are not recommended unless classification) are enclosed in this category of
in pregnant women and for individuals prior UTI. Cystitis (or lower UTI) is the most common
to perform transurethral resection of the presentation characterized by dysuria, frequency,
prostate (TURP) or other instrumental pro- urgency, suprapubic pain and sometimes hematu-
cedures responsible for mucosal bleeding ria [8, 9]. It should be highlighted that dysuria
[13]. Asymptomatic bacteriuria is reported in can be present also in women with vaginitis and
4–7% of pregnant women and should always men with urethritis, and those sexually acquired
be treated because of high risk of progression infections should be ruled out [18, 19]. Absence
to UTI including pyelonephritis (20–30-fold of vaginal discharge in a woman with dysuria and
compared with non-pregnant women) [14, 15]. urgency is indicative of UTI in more than 90% of
A Cochrane meta-analysis regarding more than cases [20].
2300 pregnant women shows that antibiotic In a study regarding women with no new vagi-
treatment is effective in terms of eradication nal discharge or change in discharge, the only
and prevention of pyelonephritis. The esti- variable predictive of STDs was more than one
mated number of individuals needed to treat to sex partner in the past year. However, it is worth
prevent one episode of pyelonephritis is seven noting that in women presenting to an emergency
[15]. Moreover, asymptomatic bacteriuria in department with genitourinary symptoms, over-
pregnant women has been associated with pre- diagnosis of UTI is common (up to 52%),
term labour and low birthweight [16, 17]. whereas sexually transmitted infection (STI) is
underdiagnosed (37%) [21]. Women are most
affected due to their anatomical conformation
3.2 Acute Uncomplicated with a self-reported annual incidence of 12% and
Urinary Tract Infections an estimated lifetime risk of UTI of 60% [22, 23].
Several risk factors for development of UTI
According to the EAU/ESIU classification, both among women have been recognized: sexual inter-
sporadic or recurrent community-acquired acute course, the use of spermicidal products, a new sex
cystitis and pyelonephritis in healthy individuals partner and a previous history of cystitis [24, 25].
3 Uncomplicated and Complicated Urinary Tract Infections in Adults 21
A possible genetic predisposition is suggested of Urology guidelines [12, 31]. Although the
although unproved by the observed increased risk three previously mentioned drugs have inferior
of recurrent cystitis and pyelonephritis among efficacy (especially fosfomycin or pivmecilli-
women reporting to have a first-degree relative nam) with respect of other antibiotics or are
with a history of UTI [26, 27]. inactive against Proteus species and some
Enterobacter and Klebsiella strains (nitrofuran-
toin) or are not approved in the United States and
3.2.1 Microbiology and Treatment some other European countries (pivmecillinam),
of Acute Uncomplicated UTI their low resistance rates together with minimal
propensity to induce “collateral damage” are the
Escherichia coli is responsible for about 80% of reason for which they are recommended as first-
all cases of uncomplicated community-acquired line choices in the setting of acute uncompli-
UTI followed by other Enterobacteriaceae (i.e., cated cystitis (Table 3.4). Nitrofurantoin should
Klebsiella spp., Proteus spp., Enterobacter spp.) not be used in patients with a creatinine clear-
and to a lesser extent gram-positive microorgan- ance (CrCL) below 60 mL/min considering the
isms (Staphylococcus saprophyticus, entero- potential risk of toxicity (especially pulmonary
cocci) [28, 29]. and neurologic toxicity), and it is considered a
A cause of concern is the increasing rate of potentially inappropriate drug for patients older
resistance to several classes of antibiotics of E. than 65 years of age [37, 38].
coli isolates from individuals with uncompli- Both fosfomycin and nitrofurantoin should
cated UTI. Trimethoprim-sulfamethoxazole not be used if pyelonephritis is suspected [5]. The
(TMP-SMX) is now considered an appropriate concept of “collateral damage” induced by some
empirical antibiotic choice for uncomplicated class of antibiotics (such as fluoroquinolones and
UTI only if the surveillance studies show resis- cephalosporins), namely, selection of drug-
tance rates under 20% [5, 8, 30, 31]. Unfortunately resistant or multidrug-resistant organisms or
several surveillance studies conducted in North increasing risk of Clostridium difficile infection,
America (USA, Canada), in Europe and in Latin gained equal weight to drug efficacy in the treat-
America (Brazil) reported resistance rates rang- ment recommendations [39]. Fluoroquinolones
ing from 16% (Canada) up to 30% in Europe and are considered for the above-mentioned reasons a
Brazil [32–35]. second choice for acute uncomplicated cystitis,
Therefore the use of TMP-SMX as an empiri- but a recent study from the USA encompassing
cal therapy for uncomplicated UTI requires the the period 2002–2011 shows that they are the
knowledge by the treating physician of the rates most frequently prescribed antibiotics (49%
of resistance in the local community and possi- overall) in the outpatient setting [40]. An even
ble risk factors associated with E. coli non- higher rate (62.7%) of prescribing a fluoroquino-
susceptible to TMP-SMX. In a Greek study, lone (i.e., ciprofloxacin) has been reported in a
patients treated with amoxicillin and/or TMP- study regarding treatment of outpatient males
SMX in the previous 3 months had a two-fold with UTI [41]. Oral β-lactam antibiotics
risk of having an infection with a TMP-SMX- (i.e., amoxicillin, amoxicillin-clavulanate, cefa-
resistant isolate [35]. Other studies showed that clor, cefpodoxime proxetil) are considered
prior use of TMP-SMX and travel outside the options when first-line agents cannot be used, but
United States in the previous 3–6 months was the increasing worldwide prevalence of extended-
predictive of TMP-SMX resistance [36]. spectrum β-lactamase (ESBL)-producing E. coli
Nitrofurantoin, fosfomycin and pivmecillinam is a matter of concern and can be associated with
are recommended as empirical first-line therapy high rates of treatment failure [2, 42, 43].
of acute uncomplicated cystitis by both the As previously discussed an episode of pyelo-
United States of America and European nephritis (or upper tract UTI) that occurs in a
Infectious Diseases Society guidelines (IDSA healthy premenopausal, non-pregnant women
and ESCMID) and by the European Association without other recognized risk factors (Table 3.1
22 S. Antinori and M.D. Pezzani
Table 3.4 Acute uncomplicated cystitis and pyelonephritis treatment recommended by IDSA/ESCMID and EAU
guidelines
Clinical syndrome IDSA/ESCMID 2012 EAU 2015
Acute cystitis First-line therapy First choice
Nitrofurantoin monohydrate/macrocrystal Fosfomycin trometamol 3 g single dose
100 mg bid for 5 days poa po
Or Or
Trimethoprim/sulfamethoxazole (TMP-SMX) Nitrofurantoin monohydrate/
160/800 mg bid for 3 days po macrocrystal 100 mg bid for 5 days poa
Or Or
Fosfomycin trometamol 3 g single dose po Pivmecillinam 400 mg tid for 5 days po
Or
Pivmecillinam 400 mg bid for 5 days po
Second-line therapy Alternatives
Fluoroquinolones Fluoroquinolonesb
Ciprofloxacin 250 mg bid for 3 days po Ciprofloxacin 250 mg bid for 3 days po
Levofloxacin 250 or 500 mg single dose for Levofloxacin 250 mg single dose for
3 days po 3 days po
Beta-lactams Ofloxacin 200 mg bid for 3 days
Amoxicillin-clavulanate Cephalosporins
Cefpodoxime-proxetil 100 mg bid for Cefadroxil 500 mg bid for 3 days po
5 days po TMP-SMX 160/800 mg bid for 3 days
pob
Acute pyelonephritis First-line therapy First choice
(mild and moderate) Ciprofloxacin 500 mg bid for 7 days po with or Ciprofloxacin 500–750 mg bid for
without an initial dose of 400 mg intravenous 7–10 days po
ciprofloxacinc Levofloxacin 500 mg/day for 7–10 days
Ciprofloxacin 1000 mg (extended release)/day po
for 7 days po Levofloxacin 500 mg/day for 5 days po
Levofloxacin 750 mg/day for 5 days po Alternativesf
Plus Cefpodoxime proxetil 200 mg bid for
1 g ceftriaxone ivd or a consolidated 24-h dose 10 days po
of an aminoglycoside Ceftibuten 400 mg/day for 10 days po
Second-line therapy Trimethoprim-sulphamethoxazole
TMP-SMX 160/800 mg bid for 14 days po 160/800 mg bid for 14 days pog
Plus
1 g ceftriaxone ive or a consolidated 24-h dose
of an aminoglycoside
(continued)
3 Uncomplicated and Complicated Urinary Tract Infections in Adults 23
Table 3.4 (continued)
Clinical syndrome IDSA/ESCMID 2012 EAU 2015
Severe acute Parenteral fluoroquinolone First choiceh
uncomplicated Ciprofloxacin 400 mg bid iv Ciprofloxacin 400 mg bid iv
pyelonephritis Levofloxacin 500–750 mg/day iv Levofloxacin 250–500 mg/day iv
Aminoglycoside Levofloxacin 750 mg/day iv
Gentamicin 5–7 mg/day iv Alternatives
Extended spectrum cephalosporin Cefotaxime 2 g tid iv
Ceftazidime 1 g tid ± an aminoglycoside iv Ceftriaxone 1–2 g/day iv
Ampicillin-sulbactam ± aminoglycoside (if Ceftazidime 1–2 g tid iv
gram-positive cocci are causative) iv Cefepime 1–2 g bid iv
Co-amoxiclav 1,5 g tid ivi
Piperacillin-tazobactam 2,5–4,5 g tid iv
Amikacin 15 mg/kg/dayi
Gentamicin 5 mg/kg/dayi
Ertapenem 1 g/day iv
Imipenem/cilastatin 0.5/0.5 g tid iv
Meropenem 1 g tid iv
Doripenem 0.5 g tid iv
IDSA/ESCMID Infectious Diseases Society of America/European Society of Clinical Microbiology and Infectious
Diseases, EAU European Association of Urology
a
Avoid in patients with glucose-6-phosphate dehydrogenase deficiency
b
If local resistance pattern is known (E. coli resistance <20%)
c
Where the prevalence of resistance of community uropathogens to fluoroquinolones is not known to exceed 10%
d
If the prevalence of fluoroquinolone resistance is thought to exceed 10%
e
When the susceptibility of TMP-SMX is not known
f
Clinical but not microbiological equivalent efficacy compared with fluoroquinolones
g
Not for initial empirical therapy
h
After improvement, the patient can be switched to an oral regimen using one of the agents listed for oral antimicrobial
therapy in mild and moderate acute uncomplicated pyelonephritis (if active against the infecting organism) to complete
1–2 week course of therapy. Therefore, only daily dose and no duration of therapy is indicated. bid twice daily, tid thrice
daily, iv intravenous
i
Not studied as monotherapy in acute uncomplicated pyelonephritis
and 3.3) is considered uncomplicated. A clinical testing for leukocyte esterase and urinary nitrites
diagnosis of pyelonephritis is suspected in the [44]. Although blood cultures are not routinely rec-
presence of fever (temperature > 38°C), chills, ommended in acute uncomplicated pyelonephritis
flank pain and costovertebral-angle tenderness; given the possibility of associated bacteremia, we
other systemic symptoms such as nausea and believe that if feasible they should be done before
vomiting or mental confusion can be present [3, antibiotic treatment. The recommendations about
4, 8, 10, 20]. Symptoms suggestive for cystitis the use of radiological techniques such as ultra-
are frequently absent. sound and computed tomography in the diagnosis
Different from suspected acute uncomplicated of acute uncomplicated pyelonephritis are out-
cystitis where urinalysis and urine culture are not side the scope of this review, and the readers are
routinely needed, in case of pyelonephritis, it is referred to the appropriate chapters in this book
recommended to always perform a urine culture dealing with this issue.
before starting empirical antimicrobial treatment Empiric antimicrobial therapy for acute
[31]. Especially in the emergency department, uncomplicated pyelonephritis should be started
patients are frequently assessed for pyuria and quickly once the diagnosis is entertained; as a
bacteriuria with commercially available dipstick general rule, an antibiotic with broad-spectrum
24 S. Antinori and M.D. Pezzani
in vitro activity against the likely uropathogens patients with short-term treatment only when
should be used (Table 3.4). Additional factors to fluoroquinolones are used [50].
be considered in choosing an appropriate empiric
drug are the local resistance data, history of expo-
sure to the same class of antibiotics in the recent 3.3 cute Complicated Urinary
A
past (a factor that increase the probability of Tract Infections
resistance), history of allergy and, if known, anti-
microbial susceptibility of previous UTI strains. As previously indicated and acknowledged by
Oral regimens that can be used for the outpatient the international guidelines, the concept of com-
treatment of less severe acute uncomplicated plicated UTI (c-UTI) refers to both structural
pyelonephritis are reported in Table 3.4. Given and functional abnormalities of the genitouri-
the high direct and indirect costs associated with nary tract or to an underlying disease that poses
hospital treatment of acute uncomplicated pyelo- an increased risk of complications or therapeutic
nephritis, there is suggestion to treat most epi- failure or poor outcome [31, 51]. This definition
sodes in the outpatient setting, but this probably does not account for severity or invasiveness of
is more frequently achieved in the USA than in the infection thus giving reason for some ambi-
Europe [45–47]. Clinical severe uncomplicated guity relative to classification, as recently sug-
pyelonephritis as well as complicated pyelone- gested [6].
phritis (risk factors and underlying disease) Male gender “per se” is considered, when a
should be always managed with hospitalization UTI is diagnosed, responsible for c-UTI; how-
of the patients. Criteria for severity of uncompli- ever, in young men without systemic symptoms
cated pyelonephritis requiring hospitalization and no medical history and/or physical examina-
include high fever (>40°C), dehydration, hypo- tion indicative of a causative factor, it is sug-
tension and high leukocyte count. gested by some authors to consider UTI as
Both IDSA/ESCMID and EAU guidelines uncomplicated [51, 52]. However, structural and
indicate fluoroquinolones as appropriate initial functional abnormalities of the urinary tract asso-
empiric antibiotic for uncomplicated pyelone- ciated with male’s ageing increase either the risk
phritis if the prevalence of fluoroquinolone or the complications of UTI [53]. Among men
resistance of community uropathogens is with febrile UTI, a study reported in more than
known to be less than 10% [12, 31]. Otherwise 90% of cases a transient increase of serum pros-
a long-acting intravenous antibiotic (i.e., ceftri- tate antigen and/or prostate volume [54]. It is
axone) should precede oral therapy, or a 24-h always important to rule out unrecognized
consolidated dose of an aminoglycoside is indi- pathologies of the urinary tract that can require
cated. The use of TMP-SMX should be reserved surgery (i.e., prostatic hypertrophy, urethral stric-
only to episodes of uncomplicated pyelonephri- ture, bladder and renal stones, bladder cancer) or
tis caused by susceptible microorganisms, and prolonged antibiotic treatment (i.e., chronic pros-
the duration of treatment was prolonged for tatitis) [54].
14 days. Oral β-lactam agents are associated
with high failure rates and should be used only
when susceptibility of causal microorganisms 3.3.1 Special Patient Groups
is known and for no more than 14 days [48].
However, a meta-analysis of randomized con- Diabetes mellitus is a well-known risk factor
trolled trials shows that for pyelonephritis for recurrent UTIs, complications (persistent
7 days of treatment is equivalent to longer treat- bacteriuria, bacteremia, bilateral renal involve-
ment in terms of clinical and microbiological ment, urosepsis) and development of life-
failure, but trials that included β-lactamase threatening peculiar picture of pyelonephritis
were old and with small number of patients such as emphysematous pyelonephritis [55–63].
[49]. For this reason it is advisable to manage Emphysematous pyelonephritis (EPN) is an
3 Uncomplicated and Complicated Urinary Tract Infections in Adults 25
an infection occurring in an individual that is cur- of c-UTI that can be applied to every circumstance
rently catheterized or has been catheterized and every patient are obviously unfeasible, and
within the past 48 h along with >103 CFU/mL of therefore it is not surprising that there are no pub-
>1 bacterial species cultured from a single cath- lished consensus guidelines. The appropriate anti-
eter urine specimen [90]. However, because signs biotic choice should consider the characteristic of
and symptoms compatible with CA-UTI are non- the patient (i.e., age, drug allergies, comorbidity),
specific (i.e., new onset or worsening fever, mal- the severity of the infection, the spectrum of pos-
aise, altered mental status, lethargy), other sible uropathogens implicated and the knowledge
possible infectious causes should be excluded of surveillance national and local data regarding
before attributing them to catheter-associated patterns of susceptibility of the d ifferent micro-
bacteriuria. The actual definition of CA-UTI was organisms [105, 106]. Moreover, the pharmaco-
introduced in 2009 excluding catheter-associated kinetic/pharmacodynamic characteristics of the
asymptomatic bacteriuria, a condition not requir- drugs and their possible interactions should be
ing antimicrobial treatment [95]. Bacteremia is considered in the appropriate choice. In general,
another complication of CA-UTI with an associ- fluoroquinolones are useless for urologic patients,
ated mortality of 9% [96]. E. coli is the single when they were previously used for the same
organism more frequently isolated in patients patient and in areas with more than 10% fluo-
with bacteriuria after short-term catheterization, roquinolone resistance. Carbapenem antibiotics
whereas infections among patients with long- have long been considered the drugs of choice
term catheterization are generally polymicrobial for infections caused by ESBL-producing micro-
and frequently with a reduced spectrum of sus- organisms [107]. However, the increasing isola-
ceptibility to most class of antibiotics [90, 97, tion of carbapenem-resistant Enterobacteriaceae
98]. The spectrum of microorganisms includes (CRE) clearly suggests the use of carbapenem-
Klebsiella spp., Enterobacter spp., Pseudomonas sparing regimens when appropriate. Cefepime
aeruginosa, coagulase-negative staphylococci, and piperacillin-tazobactam may be reasonably
Enterococcus spp., Providencia spp., Proteus alternative against ESBL-producing E. coli and
spp., Morganella spp. and Candida species [99, Klebsiella spp. when the minimum inhibitory
100]. The best way to avoid CA-UTI is to place a concentrations (MICs) are <2 μg/mL for the
urinary catheter only when strictly indispensable former drug and <16 μg/mL for the latter drug
as indicated by international guidelines as well as [108–110]. Ceftolozane-tazobactam, a recently
an early removal of it [90, 101]. Antibiotic pro- approved combination of a cephalosporin with
phylaxis is generally not recommended on the a β-lactamase inhibitor, provides better efficacy
basis of weak evidences suggesting a protective than levofloxacin in adults with c-UTI, includ-
role only in some settings [102–104]. Moreover, ing pyelonephritis [111, 112]. This is a drug of
the worldwide increase in the rate of antibiotic niche for c-UTI and should be reserved only for
resistance and the limited options of effective carbapenem-sparing regimens when other alter-
drugs in nosocomial-acquired infections are natives are not suitable and for multidrug-resistant
other reasons for not using prophylaxis for cath- (MDR) Pseudomonas aeruginosa. Another car-
eterized patients. bapenem-sparing drug regimen that can be used
for c-UTI caused by MDR microorganisms is
the combination of ceftazidime with avibactam,
3.3.2 M
anagement of Complicated a non-β-lactam β-lactamase inhibitor which is
UTI able to restore the in vitro activity of ceftazidime
against ESBL and K. pneumoniae carbapenemase
Before starting an antibiotic treatment, c-UTI and Ambler Class C (i.e., AmpC) and some class
patients should undergo a urine culture as D β-lactamase-producing bacteria. It is not active
well as a blood culture when it is appropriate. against metallo-β-lactamase. In a randomized
Recommendations regarding empirical treatment controlled trial, ceftazidime- avibactam dem-
3 Uncomplicated and Complicated Urinary Tract Infections in Adults 27
onstrates superiority versus doripenem for the rates is essential. More recent data from EARS-
treatment of c-UTI including acute pyelonephri- Net, the largest European surveillance system on
tis [113]. However, to preserve its efficacy as a antimicrobial resistance, shows that for E. coli
salvage therapy for CRE, the use of ceftazidime- isolates from invasive infections, the population-
avibactam should be reserved for severe c-UTI weighted mean percentage for fluoroquinolone
caused by MDR microorganisms [114]. resistance is 22.8% in 2015 [78]. However, eight
countries (Greece, Romania, Spain, Bulgaria,
Malta, Slovakia, Italy and Cyprus) had resistance
3.4 Urosepsis prevalence higher than 30%. Among the E. coli
isolates that are resistant to third-generation ceph-
Urosepsis is generally defined as a sepsis in alosporins (mean percentage 13.1%), 88.6% were
which the source of the infection is the urinary ESBL-positive. The resistance to carbapenems
tract and/or the prostate (in males) [115]. of E. coli in Europe remained rare with only two
Urosepsis represents about 25% of all cases of countries (Greece and Romania) with reported
adult sepsis and 5% of cases evolving to severe resistance rates above 1%. Combined resistance to
sepsis and septic shock [116, 117]. third-generation cephalosporins, fluoroquinolones
Obstructive uropathy is responsible for about and aminoglycosides ranged from 0% (Iceland)
78% of cases of urosepsis with urolithiasis being to 17.1% (Slovakia) [78]. Antibiotic resistance
the most frequent cause [118, 119]. A recent sys- against K. pneumoniae is a cause of concern in
tematic review that aimed to identify risk factors Europe with more than one third of isolates reported
for urosepsis and urosepsis-related mortality in in 2015 that were resistant to at least one antimi-
older adults concluded for the lack of quality evi- crobial under surveillance (i.e., fluoroquinolones,
dence regarding risk factors [120]. It should be rec- aminoglycosides, third-generation cephalosporins
ognized that a new sepsis definition published in and carbapenems) and 4.7% of all K. pneumoniae
2016 has been adopted, but several concerns have isolates resistant to all groups of antibiotics. An
raised, and its applicability in the field of urosepsis increasing rise of carbapenem-resistant strains was
is presently unknown [121–123]. The administra- observed with three countries (Greece, Italy and
tion of an initially adequate intravenous antibiotic Romania) with reported resistance percentages
is essential for optimal outcome, but inadequate higher than any other country (61.9%, 33.5% and
coverage in urosepsis may be a problem due to 24.7%, respectively) [78]. Moreover, the high per-
the lack of solid microbiological data [124]. In a centages of ESBL-positive K. pneumoniae resis-
German study regarding sepsis, the bacterial spec- tant to third-generation cephalosporins (85.3%)
trum of urosepsis consisted of E. coli in 61% of may lead to an increased use of carbapenems with
cases, followed by other enterobacteria in 16%, an obvious increase of carbapenemase-producing
S. aureus in 8% and enterococci in 6% of cases Enterobacteriaceae. As far as Pseudomonas aeru-
[125]. A recent point prevalence study conducted ginosa is concerned, MDR was observed cumula-
in 70 countries from 2003 to 2013 shows that the tive for 5.5% of the isolates with also a confirmed
overall prevalence of E. coli as a cause of urosep- increasing trend of resistance to piperacillin-tazo-
sis was 43% followed by Enterococcus spp. (11%) bactam (from 16.7% in 2012 to 18.1% in 2015)
and Klebsiella spp. (10%) and Pseudomonas aeru- [78]. Carbapenems resistance of P. aeruginosa
ginosa (10%) [126]. Patients with a diagnosis of is also high (>25% of isolates) in eight countries
urosepsis had the highest resistance rates to all (Bulgaria, Lithuania, Hungary, Poland, Croatia,
class of antibiotics compared with patients with Greece, Slovakia and Romania). High-level gen-
other healthcare-associated urinary tract infections tamicin resistance of Enterococcus faecalis was
(HAUTI) [126]. Overall resistance to fluoroquino- reported in 31.3% of isolates in 2015 with seven
lone in Europe was reported to be 59%, 42% for countries (Spain, Bulgaria, Lithuania, Hungary,
ceftazidime and 34% for piperacillin-tazobactam, Poland, Italy, Slovakia) having percentages higher
but as highlighted knowledge of local resistance than 40%. A significant increase of vancomycin-
28 S. Antinori and M.D. Pezzani
resistant E. faecium was observed in 12 countries, adhesion blockers (i.e., d-mannose) are some-
although the increase at European level from 2012 times useful [8, 12, 129]. Antimicrobial pro-
to 2015 (8.1% and 8.3%) was not statistically phylaxis with long-term low dose antibiotics or
significant. Since enterococci have intrinsic resis- post-coital antibiotic prophylaxis is the alternative
tance to several classes of antibiotics and display strategy. It is generally employed with nitrofuran-
the ability to acquire additional resistance, the epi- toin (100 mg per day), cephalexin (250 mg daily),
demiologic situation regarding these bacteria is fosfomycin (3 g every 10 days) or trimethoprim-
harmful owing to their role in HAUTI. sulfamethoxazole (40/200 mg daily) with an
When urosepsis is suspected, blood cultures important reduction of the risk of recurrences
are mandatory before starting empiric antimicro- [27, 130]. It should be highlighted that after stop-
bial therapy, whereas urine cultures have a low ping prophylaxis, women experience pretreat-
sensitivity and specificity in the presence of ment rates of infection. Moreover, the increasing
obstructive pyelonephritis [118]. Procalcitonin antimicrobial resistance needs to be considered
(PCT) is the best and more rapid biomarker of because many antibiotics commonly employed
systemic inflammation and if available should be to treat UTI are now ineffective [131]. Finally,
used for patients with suspected urosepsis. In a the so-called patient-initiated treatment strategy
prospective observational study, a single determi- should be considered for motivated women. This
nation using a cut-off of PCT > 0.25 μg/L had the means that women learn to recognize signs and
best diagnostic performance (sensitivity 95%, symptoms of cystitis and undergo a self-treatment
specificity 50%) in predicting bacteremia among with a 3-day course of an antimicrobial [27, 129].
patients with urosepsis [127]. Despite the fact that
the investigators of the above-cited trial suggested Conclusions
that adopting a PCT threshold of <0.25 μg/L can Urinary tract infections are among the most
be associated with a 40% of blood culture utiliza- frequent infectious complications with a high
tion, we believe that the appropriate use of PCT in impact in terms of suffering for the patients
this setting is not as a blood culture sparing bio- and cost for the healthcare systems. The
marker but as a guide to stop antibiotics [128]. increasing worldwide antimicrobial resistance
of Enterobacteriaceae with ESBL and
carbapenemase-producing microorganisms
3.5 Recurrent UTI poses a high risk of treatment failure espe-
cially among hospitalized frail patients.
Recurrent UTI is frequently observed among Antimicrobial stewardship programme should
young healthy women without any urological be urgently implemented, and physicians need
alteration, and it is defined as three or more uri- to be aware of “collateral damage” induced by
nary tract infections in the past 12 months or two several antibiotics and educated to use them
episodes in the past 6 months (with at least one accordingly with the appropriate guidelines.
confirmed by a positive culture) [27]. Although
several risk factors have been identified or sus-
pected (use of spermicides; sexual intercourse;
new sexual partner; tampon use; a relative with
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Perspective from the Urologist
4
Ai Ling Loredana Romanò
and Antonio M. Granata
to culture. A colony count of ≥103 CFU/mL of bacteria in the lymphatics. Host and microbial fac-
uropathogen is diagnostic [4]. Escherichia coli is tors that underlie progression from bladder to kid-
the main microorganism involved in the ney infection require further investigation.
pathogenesis.
Radiographic imaging is not necessary to
diagnose cystitis. Ultrasound (US) can point out 4.3.2 Clinical Manifestations
mucosal oedema associated with a diffuse thick-
ening of the bladder wall. In clinical practice, it is Acute pyelonephritis is suggested by flank pain,
required in case of recurrent episodes. Generally nausea and vomiting, fever (>38 °C), chills and
it is more useful to rule out some complications, costovertebral angle tenderness. Symptoms of
such as bladder stones or other bladder diseases cystitis may or may not be present [11]. Patients
(tumours). Other radiological examinations don’t with acute complicated pyelonephritis may pres-
add any important information. ent with sepsis. In some cases they may be asso-
ciated with a period of insidious, non-specific,
signs and symptoms such as malaise, fatigue or
4.2.3 Disease Management abdominal pain. In diabetic patients acute pyelo-
nephritis may also develop progression of renal
Antibiotic therapy is recommended in symptom- parenchymal infection sometimes caused by gas-
atic patients. The first choice in many European forming organisms (emphysematous pyelone-
countries are fosfomycin 3 g single dose, pivme- phritis), with a high mortality [12].
cillinam 400 mg tid for 3 days and nitrofurantoin The risk of chronic renal disease and renal
100 mg bid for 5 days [5–7]. insufficiency caused by pyelonephritis is low.
Alternative antibiotics include trimethoprim It is important to differentiate very early
combined with sulphonamide and fluoroquino- between an acute uncomplicated and compli-
lone class (ciprofloxacin, levofloxacin) in 3-day cated obstructive form of pyelonephritis, because
regimens. the latter can very quickly lead to urosepsis.
In case of complicated cystitis or suspected
concomitant pyelonephritis, oral therapy with
fluoroquinolones becomes the first choice. 4.3.3 Diagnostic Evaluation
Patients with persistent clinical symptoms remotely reported and is the one that offers more
after 48–72 h of appropriate antibiotic therapy information at one time, especially with regard to
should undergo radiologic evaluation of the complications. MRI would be preferable but not
upper urinary tract, initially with US. In addition, always, and not in all hospitals, there is a real
radiologic evaluation is warranted for patients chance to perform such an examination in emer-
with pyelonephritis who also present symptoms gency conditions.
of renal colic or have history of renal stones, dia-
betes, history of prior urologic surgery, immuno-
suppression, repeated episodes of pyelonephritis 4.3.4 Disease Management
or urosepsis [13].
Evaluation of the upper urinary tract with US Empiric antimicrobial therapy should be initi-
should be performed to rule out urinary obstruc- ated promptly. In mild and moderate cases of
tion or renal stone disease. Computed tomography acute uncomplicated pyelonephritis, oral therapy
(CT) scan should be considered if the patient still for 10–14 days is usually sufficient. The first-
presents fever after 72 h of treatment. CT without line therapy is represented by fluoroquinolone
contrast has become the standard radiographic (Table 4.1), contraindicated in pregnancy. A
study for demonstrating gas-forming infections, third-generation oral cephalosporin could be an
haemorrhage, obstruction and abscesses. Contrast alternative in case of resistance. In communities
is needed to demonstrate localized hypodense with high rates of fluoroquinolone-resistant and
lesions due to ischaemia. Magnetic resonance ESBL-producing E. coli, initial empirical ther-
imaging (MRI) is preferred in pregnant women to apy with an aminoglycoside or carbapenem has
avoid radiation risk to the foetus. to be considered.
In clinical practice CT remains the most used In patients with severe pyelonephritis, par-
exam because it is widely available, can be enteral antibiotics have to be used. After
improvement, the patient can be switched to an Table 4.2 Diagnostic criteria for sepsis
oral therapy for 1–2 weeks. Positioning urinary • General signs
catheter is important in order to drain the uri- – Fever >38.3 °C
nary tract. – Hypothermia <36 °C
– Tachycardia >90/min or >2 SD above
age-specific normal value
4.4 Urosepsis – Tachypnea >30/min
– Impaired neurologic status
Sepsis is a complex systemic inflammatory host – Oedema or positive fluid balance (>20 mL/
kg/d)
response to bacterial infection (Table 4.2). In
– Hyperglycemia (blood sugar >120 mg/dL or
urosepsis the focus of infection is localized to 7.7 mmoL/L) in the absence of previously
the urogenital tract. Patients with urosepsis diagnosed diabetes mellitus
should be identified at an early stage and • Signs of inflammation
promptly treated to prevent development of – Leukocytosis >12/nL
organ failure and other complications. Mortality – Leukopenia <4/nL
rates are high. The severity depends mostly upon – Normal leukocyte count with >10% immature
the host response. forms
– C-reactive protein >2 SD above normal
– Procalcitonin >2 SD above normal
4.4.1 Pathogenesis • Hemodynamic signs
– Hypotension (SBP <90 mmHg, MAP
<70 mmHg or SBP drop by >40 mmHg or to <2
Complicated UTI is the commonest precursor of SD below the age-specific normal value)
urosepsis. It is important to note that a patient can – Cardiac index (CI) >3–5 L/min/m2
move from an almost harmless state to severe • Organ dysfunction
sepsis in a very short time. Structural and func- – Arterial hypoxemia (paO2/FiO2 < 300)
tional abnormalities such as obstruction (congen- – Acute oliguria <0.5 mL/kg/h or 45 mmoL/L for
ital or acquired), instrumentation, impaired (≥ 2 h)
voiding, metabolic abnormalities and immunode- – Creatinine rise by (≥ 0.5 mg/dL)
ficiencies can be associated to urosepsis. – Coagulopathy (INR >1.5 or aPTT >60 s)
Microorganisms reach the urinary tract byway – Thrombocytopenia <100/nL
of the ascending, haematogenous or lymphatic – Hyperbilirubinemia (total bilirubin >4 mg/dL
routes. For urosepsis to be established, the patho- or >70 mmoL/L)
– Ileus
gens have to reach the bloodstream. Gram-
• Tissue perfusion variables
negative bacilli account for majority of the cases
– Lactate >2 mmol/L
of urosepsis. These include E. coli (50%), Proteus
– Decreased capillary refill or mottling
spp. (15%), Enterobacter and Klebsiella spp.
(15%) and Pseudomonas aeruginosa (5%), while
Gram-positive organisms are involved less fre- symptoms [16]. Fever, tachycardia, tachypnea
quently (15%) [14]. and respiratory alkalosis are the typical mani-
festation. Only one-third of the patients classi-
cally present with fever and chills along with
4.4.2 Clinical Manifestations hypotension.
biotic use and a timeline of symptoms. A patient Empirical antimicrobial therapy effective
can be considered to have sepsis if he or she has against both Gram-positive and Gram-negative
evidence of bacteremia or clinical suspicion of bacteria should be initiated. A calculated paren-
sepsis accompanied by greater than or equal to teral antibiotic should be reassessed once culture
two criteria of systemic inflammatory response results become available, usually within 48–72 h.
syndrome as mentioned in Table 4.2. In case of E. coli and other Enterobacteriaceae
The diagnosis of UTI, from simple cystitis to isolation, a third-generation cephalosporin or
complicated pyelonephritis with sepsis, can be piperacillin in combination with a beta-lactamase
established with absolute certainty only by quan- inhibitor or fluoroquinolone with propensity to
titative urine cultures. achieve high urinary concentration (e.g. cipro-
Blood cultures should be done before antibi- floxacin, levofloxacin) should be used. A combi-
otic treatment is started. Ideally, several aerobic nation therapy with an aminoglycoside or a
and anaerobic blood cultures are taken when carbapenem may be essential in areas with high
fever is rising. rate of fluoroquinolone resistance. Reserve anti-
In a critically ill patient with urosepsis, CT biotics such as imipenem or meropenem if a dif-
and MRI are very useful investigations. These are ficult resistance situation is suspected [18].
the most precise methods for identifying bacte-
rial interstitial nephritis and micro-abscesses
within the kidney, perinephric abscesses, emphy-
sematous pyelonephritis and renal papillary References
necrosis and can determine therapeutic choices
1. Foxman B (2002) Epidemiology of urinary tract
and intervention times. Urinary unblocking, with infections: incidence, morbidity and economic costs.
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tomy, is mandatory. 2. Gupta K, Hooton TM, Naber KG et al (2011)
International clinical practise guidelines for the treat-
ment of acute uncomplicated cystitis and pyelonephri-
tis in women: a 2010 update by the infectious diseases
4.4.4 Disease Management Society for Microbiology and Infectious Diseases.
Clin Infect Dis 52:103
The treatment of urosepsis needs the collabora- 3. Stamm WE (1997) Urinary tract infections in young
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J- MJ) or percutaneous nephrostomy. with diabetes mellitus. Clin Nephrol 77(1):40–48
10. Naber KG et al (2008) Surveillance study in Europe and
If possible, specific treatment of the diag- Brazil on clinical aspects and antimicrobial resistance
nosed infection should be started as soon as epidemiology in female with cystitis (ARESC): impli-
possible. cation for empiric therapy. Eur Urol 54(5):1164–1175
40 A.L.L. Romanò and A.M. Granata
11. Scholes D et al (2005) Risk factors associated with in sepsis. The ACCP/SCCM consensus conference com-
acute pyelonephritis in healthy women. Ann Intern mittee. American College of Chest Physicians/Society
Med 142(1):20–27 of Critical Care Medicine. Chest 101(6):1644–1655
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renal failure. In: Raine AE (ed) Advanced renal medi- ATS/SIS international sepsis definitions conference.
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14. Wagenlehner FM, Weidner W, Naber KG (2007)
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Perspective from the Andrologist
5
Antonio Maria Granata
and Ai Ling Loredana Romanò
The male reproductive tract consists in exter- ally associated with mumps infection in prepu-
nal structures such as the penis, scrotum, testis, bertal boys (13 years or younger).
and internal structures including the prostate The incidence can be described with a bimodal
gland, epididymis, vas deferens, and seminal distribution, occurring in young adults with the peak
vesicles. incidence between 16 and 30 years of age; the other
Male reproductive tract infections (MRTIs) peak incidence is present in 51–70 years of age.
are very common diseases of the genital sys- In epididymitis, the most usual route of infec-
tem. These infections are caused by bacteria, tion is the retrograde ascent of pathogens, and bac-
virus, or other organisms and can be either teria are frequently responsible, with different age
endogenous, iatrogenic, or sexually transmit- distribution: in the first age group (16–30 years),
ted. All those infections have a higher inci- the most common pathogens are sexually transmit-
dence after urologic procedures, such as ted, such as Chlamydia trachomatis, Ureaplasma
prostatic biopsy, indwelling, or intermittent urealyticum, and Neisseria gonorrhoeae. In the
catheter. Chronic infections of epididymis and second group (51–70 years), the primary patho-
prostate are frequently associated with urine gens are coliform bacteria, coming from urinary
voiding dysfunctions that cause high pressure tract, and the infections are frequent consequence
and reflux in genital duct. of voiding dysfunctions. Escherichia coli is the
most frequent causative pathogen; nevertheless
other common microbial agents are Haemophilus
5.1 Epididymitis and Orchitis i., Proteus mirabilis, Klebsiella pneumoniae, and
Pseudomonas aeruginosa.
Inflammation of epididymis and testes generally Mycobacterium tuberculosis, fungi, and virus,
results from infection; epididymitis is the most including cytomegalovirus, are uncommon caus-
common infection, but in some case when inflam- ative agent but have to be strongly considered in
mation spreads to the adjacent testicle, orchitis HIV patients.
can develop. Isolated orchitis is rare and is gener- Epididymitis and orchitis are classified as
acute or chronic processes according to the onset
and clinical course. Epididymitis is almost
A.M. Granata (*) • A.L.L. Romanò always unilateral and relatively acute in onset. In
Urology Department, ASST FBF Sacco—Ospedale young males it is frequently associated with sex-
Luigi Sacco, Via G.B. Grassi 74, Milan 20157, Italy ual activity and infection of the consort. The
e-mail: antonio.granata@asst-fbf-sacco.it; ailing. majority of cases in sexually active males aged
romano@asst-fbf-sacco.it
<35 years are due to sexually transmitted organ- The color Doppler equipment should be cali-
isms, whereas in elderly patients, it is usually due brated to demonstrate blood flow in the normal
to common urinary pathogens. testis. For flow measurements, the Doppler cur-
Epididymitis causes pain and swelling, which sor must be positioned within the testis. When
begins in the tail of the epididymis and may normal or increased flow is demonstrated, torsion
spread to involve the rest of the epididymis and is excluded. Conversely, in epididymitis and
testicular tissue. The spermatic cord is usually orchitis, hypervascularization of both epididymis
tender and swollen. and testis is commonly found [4].
History and physical examination are thus
very important to achieve a diagnosis, especially
to exclude sperm cord torsion. 5.2 rostatitis and Infections
P
The differential diagnosis between epididymi- of Seminal Vesicles
tis and testicular torsion is one of the most fre-
quent problems for the urologist attending the The most used classification of prostatitis was
emergency room, because torsion is a surgical published in 1999 by the National Institutes of
emergency and the likelihood of testicular salvage Health (NIH) and includes four categories: acute,
decreases as the duration of torsion increases. chronic bacterial prostatitis, chronic pelvic pain
The microbial aetiology of epididymitis can syndrome (CPPS), and asymptomatic inflamma-
sometimes be determined by examination of a tory prostatitis.
urethral swab and/or a urine culture [1]. Acute prostatitis and chronic bacterial prosta-
Fluoroquinolones with activity against C. tra titis are defined by documented bacterial infec-
chomatis (e.g. ofloxacin and levofloxacin) should tions of the prostate. The isolation of bacteria
be the drugs of first choice. If C. trachomatis has allows the differentiation of chronic prostatitis
been detected, treatment could also be continued from CPPS and asymptomatic inflammatory
with doxycycline, 200 mg/day, for a total of at least prostatitis. According to the duration of symp-
2 weeks, and the sexual partner should also be toms, prostatitis is considered chronic when
treated [2]. In abscess-forming epididymitis or symptoms persist for at least 3 months [5].
orchitis, or in patients not responding to antibacte- Bacterial prostatitis may be caused by ascend-
rial treatment during the first 72 h, surgery should ing infection through the urethra, refluxing urine
be considered [3]. In severe cases an abscess into prostate ducts, or direct extension or lym-
involving the testis may even require orchiectomy. phatic spread from the rectum.
Chronic epididymitis can sometimes be the Approximately 80% of the pathogens are
first clinical manifestation of urogenital Gram-negative organisms (e.g., Escherichia coli,
tuberculosis. Enterobacter, Serratia, Pseudomonas,
Complications in epididymo-orchitis include Enterococcus, and Proteus species) [6]. Sexually
abscess formation, testicular infarction, testicular transmitted agents like Neisseria gonorrhoeae
atrophy, reactive hydrocele, development of and Chlamydia trachomatis can also cause
chronic epididymal induration, and infertility. prostatitis.
In HIV-infected patients, viral and granuloma-
tous prostatitis may be present, caused by virus
5.1.1 Imaging as Cytomegalovirus (CMV), Mycobacterium
tuberculosis, or fungi, such as Candida albicans
In the differential diagnosis of sperm cord tor- [7, 8].
sion, to improve diagnostic accuracy and avoid As described in epididymitis, sexually trans-
unnecessary surgery, color Doppler ultrasonogra- mitted agents are frequently encountered in
phy has become the preferred imaging technique young patients, coliform bacteria in older man
for evaluating the acute scrotum. with voiding dysfunctions.
5 Perspective from the Andrologist 43
The process that leads to a chronic bacterial Fluoroquinolones provide relief in about 50%
prostatitis can include an insufficient initial ther- of patients, and treatment is more effective if
apy or, often, some concomitant voiding dysfunc- treatment starts earlier in the course of symp-
tion problem; E. coli is responsible for 75–80% of toms [10].
chronic bacterial prostatitis cases; Entero
cocci, Pseudomonas, Chlamydia trachomatis,
Ureaplasma urealyticum,and Trichomonas vagi 5.2.1 Imaging
nalis are usually isolated in the remainder of
cases. Suprapubic ultrasonography is routinely used to
Patients with acute bacterial prostatitis can assess volume of retained urine in cases of prostati-
manifest with fever, perineal pain, lower urinary tis associated with significant voiding dysfunction.
tract symptoms, and spontaneous urethral dis- On transrectal ultrasonography (TRUS), a
charge. Conversely, those with chronic bacterial hypoechoic halo in the periurethral region and a het-
prostatitis typically have no systemic symptoms erogeneous echo pattern can often be seen.
but sovrapubic, testicular, or perineal pain and However, it is not so reliable for the diagnosis of
lower urinary tract symptoms [9]. prostatitis; thus it is not routinely indicated in
Digital rectal examination in patients with patients with acute prostatic symptoms. Moreover
acute bacterial prostatitis may reveal a tender, during an episode of acute prostatitis, transrectal
hot, and painful gland. Prostatic massage should ultrasonography can be very painful; thus it has to
be avoided to reduce the risk of bacterial be definitely avoided.
spreading. Imaging has indeed a very important role
The most important investigation for bacte- when an abscess is suspected [11]. A TRUS in
rial identification in acute prostatitis is the urine many can be sufficiently accurate and can be
culture. In chronic bacterial prostatitis, a used during a perineal drainage.
Meares-Stamey test analyzing segmented urine In other situations, magnetic resonance imag-
and of expressed prostatic secretion (EPS) is ing (MRI) is helpful, for example, in case of
needed [10]. immunodeficient patients with unclear perineal
Pyospermia and hematospermia in men in endemic symptoms.
regions or with a history of tuberculosis should be
investigated for urogenital tuberculosis [8].
Patients with acute bacterial prostatitis who 5.3 Fournier’s Gangrene
appear acutely ill or with have evidence of sep-
sis require hospital admission for parenteral The scrotum can be frequently involved during
antibiotics and supportive care [6]. Antibiotic orchitis and epididymitis, and in these cases the
therapy should initially include parental bacteri- cutaneous and subcutaneous infection responds
cidal agents such as broad-spectrum penicillin to a basic antibiotic therapy.
derivatives, third-generation cephalosporins The crucial differential diagnosis is Fournier’s
with or without aminoglycosides, or fluoroqui- gangrene, an aggressive and frequently fatal cat-
nolones. Patients without toxic symptoms can egory of necrotizing fasciitis, characterized by a
be treated on an outpatient basis with a 14- to polymicrobial soft tissue infection of the
28-day course of oral antibiotics, usually a fluo- perineum, perianal region, and external genitalia.
roquinolone or trimethoprim-sulfamethoxazole. Fournier’s gangrene remains rare, but its inci-
In cases of prostatic abscess, it has to be dence is increasing with an ageing population,
drained under local anesthesia either transrectally higher prevalence of diabetes, and emergence of
or transperineally. multiresistant pathogens [12].
For the chronic bacterial prostatitis, a 4- to Risk factors include immunosuppression, dia-
6-week of antibiotic therapy is indicated. betes, obesity, and malnutrition. Fournier’s gan-
44 A.M. Granata and A.L.L. Romanò
Giorgina Barbara Piccoli and Francesca Ragni
Acute pyelonephritis (APN), first described in Thirdly, the relationship with predisposing
Egyptian medicine, has been known for over two factors is complex. This confusion is reflected in
millennia [1]. Descriptions of the risk of death the current terminology: the adjectives compli-
due to sepsis and of evolution into subacute forms cated and noncomplicated pyelonephritis define
ultimately resulting in uraemia and death are over the presence of predisposing factors and not the
200 years old [1]. Yet there is still much that effect of a severe disease. The issues of preg-
needs to be known about this life-threatening and nancy in adults, of reflux in children, and of kid-
relatively widespread condition, and, as this short ney transplantation are also a part of this complex
nonsystematic, critical review will discuss, noth- series of factors.
ing is simple in APN. Fourthly, partly as a consequence of the previ-
Firstly, we lack a clear, standard definition, ous points, the outcomes of treatment and, conse-
whereas APN is currently seen both as a paren- quently, treatment schedules change remarkably.
chymal disease, defined by imaging, and as an Should we be concerned about kidney scars? Do
upper urinary tract infection, defined on clinical we need to look for them?
bases. This review will discuss these open questions
Secondly, while in children APN is consid- with particular regard to their practical implica-
ered a parenchymal disorder, which may be tions, leaving the pathogenetic issues and treat-
linked with vesicoureteral reflux, in adults it is ment schedules to the chapters which deal
seen as an upper urinary tract disorder, not neces- specifically with these topics.
sarily requiring imaging confirmation.
aged by nephrologists and complicated APN by the ment of the kidney parenchyma by imaging or by
urologists; in Germany urology is the main setting a renal biopsy, as will be further discussed.
of care, while in other parts of the world, the disease According to this morphologic definition, there
is treated in internal medicine, emergency medicine are two different types of involvement of the
or infectious diseases, while paediatricians are the upper urinary tract: pyelonephritis, in which there
main interveners in children [2–7]. No wonder, is a demonstrated involvement of the renal tissue;
therefore, that management, approaches and focus and cystopyelitis, in which the infection, which
are different, as this book itself also shows. has a superimposable clinical presentation, is lim-
The main focus for infectious disease and inter- ited to the renal pelvis and no sign of parenchyma
nal medicine specialists is healing the active pyelo- involvement is found at imaging [17].
nephritis lesions; urologists are more concerned This classic morphologic definition has the
about predisposing factors and nephrologists with advantage of distinguishing between two types of
long-term consequences. As a further result, the lesions that, in spite of a similar presentation, can
imaging employed may vary according to the set- have a different clinical course—more severe in the
ting of care, while nephrologists are principally presence of parenchyma involvement, with sever-
interested in kidney scar development and will tend ity that may be proportional to the extension of that
to focus not only on defining the initial disease but involvement and to the presence of abscessed
also on determining whether there is residual dam- lesions. However, the drawback of the morpho-
age (kidney scars), a focus shared with paediatri- logic definition is that it requires a “second-line”
cians and internal medicine and infectious disease imaging test (contrast-enhanced CT scan, nuclear
specialists which are more concerned with the magnetic resonance—MRI—or renal scintigra-
severity of the disease and may limit imaging to phy), since renal ultrasound, which is relatively
clinically severe cases and to the initial diagnostic inexpensive and easily available and is therefore of
phase [8–12]. Conversely, paediatricians and urolo- pivotal importance for the demonstration of
gists are more prone to investigate the presence of mechanic predisposing factors (obstruction, mal-
predisposing factors and more frequently ask for a formation, ectopic kidney, dilatation), is not reli-
search for vesicoureteral reflux, even in the absence able in distinguishing the parenchymal lesions of
of a true reflux nephropathy, characterised by ure- pyelonephritis unless they are abscessed [21–24].
teric dilatation and tortuosity [8, 13–15]. Therefore, faced with the pressure of cost con-
The issue is still open and will probably remain straints, at least for adult patients, the most com-
so; indeed, more than 20 years ago, in a well- monly used definitions are solely clinical, based
grounded, lucid paper that is still pertinent to the on the classic tetrad of fever, costovertebral ten-
issues we currently face, Talner commented on the derness, positive urinary culture and lower uri-
lack of agreement on the terminology of APN and, nary tract symptoms. The term upper urinary
as a consequence, on the lack of univocal diagnos- tract infection encompasses both of the forms
tic definitions of this disease [16]. Since in medi- mentioned above (cystopyelitis and acute pyelo-
cine, the lack of a definition is a lack of a diagnosis nephritis) and proposes clinical triage at referral
and the lack of a diagnosis often means a lack of and response to empiric treatment after referral
agreement on treatment, this problem is not only a as selection criteria for which cases should
semantic one. In fact it may be one of the reasons undergo imaging evaluation [25–31]. These
for the lack of conformity in diagnostic and thera- selection criteria mainly include the severity of
peutic approaches to a disease that has been known the initial presentation, the lack of rapid response
to medicine for over two millennia [17]. to therapy or a short-term relapse of a symptom-
According to the most commonly found, sim- atic infection. Both approaches have a strong
ple (possibly simplistic), “classic” textbook defi- logic, and both can prove effective. However, in
nition, acute pyelonephritis (APN) is a severe the absence of a comparison between a morpho-
infectious disease involving the pelvis, calices logic and a clinical approach to APN, the choice
and kidney parenchyma [17–20]. Such a defini- relies on organisation, opinions and health-care
tion obviously implies demonstrating the involve- differences, as will be further discussed.
6 Nothing Is Simple in Acute Pyelonephritis: A Pragmatic, Semantic Nephrologist’s View 47
systemic factor is identified [16, 17, 37, 39, 45, noncomplicated APN is almost exclusively a dis-
46]. According to this definition, complicated ease of women, in particular those of childbearing
forms encompass also APN in kidney graft and age. The rarity of APN in young men has led some
APN in pregnancy. While this distinction is still experts to conclude that by definition APN in a
the main reference, the presence of renal male subject is “complicated” [41–43].
abscesses is considered by some authors as a fac- In elderly males, prostatic hypertrophy is the
tor defining a “complicated APN”, considering, most common cause of APN, while in postmeno-
this time, the adjective complicated linked to the pausal women, tissue atrophy and uterine pro-
disease process itself. lapse are frequent concomitants [47–49].
The epidemiology of APN varies according to The absence or presence of predisposing factors
age and sex. conditions the choice of therapeutic approaches
As previously mentioned, in children, APN is employed to correct them. Their severity and
often, even if possibly not always, the result of complexity ultimately determine the therapeutic
vesicoureteral reflux; hence, it’s more often “com- response. In this regard, imaging is subordinated to
plicated” in this age group [32–36]. Conversely, the underlying problem (Table 6.1).
Table 6.1 Indications, advantages and limits of the most widely used imaging tests in acute pyelonephritis. A nephro-
logical view
Imaging test Potential indications and advantages Limitations
Ultrasound (US) Easily available, inexpensive, often feasible in Not able to distinguish between normal
the emergency room. Indicated in all cases, to parenchyma and non- abscessed
distinguish between complicated and lesions
noncomplicated APN. Can also detect
abscessualised lesions
Contrast-enhanced US Does not involve for radiation, often feasible in Relatively high cost, operator
the emergency room. A good choice in dependent, no standardisation and lack
experienced hands of agreed assessment of sensibility and
specificity
CT scan with contrast First gold standard imaging technique. Rapidly Ionising radiation exposure; need for
media available in most settings; may be of use in contrast media. Limitations in
particular in cases in which a further surgical allergic patients. Use only when
approach is foreseen (complicated APN). Can absolutely necessary for women of
be the first choice where MRI is not available, childbearing age
in particular in elderly women or in males, in
which complicated APN is expected and
radioprotection is less crucial
Magnetic resonance At least comparable to CT scan in terms of Need for gadolinium-enhanced media.
imaging (MRI) with sensibility and specificity. No need for ionising Not feasible in claustrophobic patients.
contrast media radiations and, therefore, first choice for Expensive, not always readily
women of childbearing age available. Long test, not easy to use
with children
Magnetic resonance Less experience but results probably similar to Not feasible for claustrophobic
imaging (MRI) those obtained using MRI with contrast media patients. Expensive, not readily
without contrast media in terms of sensibility and specificity. No need available. Relatively long test, not easy
including diffusion- for ionising radiations, so the first choice for to use with children. As in all relatively
weighted imaging women of childbearing age and for pregnant new techniques, results may depend on
(DWI) women radiologist’s experience
DMSA scintigraphy First choice for children, provides useful Exposure to ionising radiations; not
information on parenchymal involvement. able to distinguish between recent,
Feasible with assistance; does not require healed and new lesions
nephrotoxic media
MAG 3 scintigraphy Can provide useful information on “minor” Nonstandardised. Exposure to ionising
predisposing factors, including ureteral radiations; not able to distinguish
dyskinesia between recent, healed and new lesions
6 Nothing Is Simple in Acute Pyelonephritis: A Pragmatic, Semantic Nephrologist’s View 49
after kidney transplantation) and nephrotoxic or While we know something about it, namely,
potentially teratogenic agents. the pathogens that cause it, the imaging that is
Nor does the review deal with the problem of required to make a diagnosis and what short-term
infections in the renal cysts, discussed elsewhere follow-up should be, we know less about the
in this book, or rare infections, such as emphyse- long-term effect of kidney scars, how long treat-
matous APN and tuberculosis. We refer readers ment should continue and what the effect of treat-
interested in these topics to other chapters in the ment duration on kidney scars is. The
book (insert). nephrologist’s conclusions can thus be sum-
marised into two sentences.
Do not think that we know everything there is
6.6 onclusions: Why We Need
C to know about APN. Before applying guidelines,
Further Research test the inclusion and exclusion criteria of the main
RCTs with the data available for each population.
APN is an ancient disease, yet much remains to A prospective randomised trial is probably
be learned about it. needed to asses duration of therapy in a setting in
52 G.B. Piccoli and F. Ragni
which imaging is done at referral and before 10. De Pascale A, Piccoli GB, Priola SM, Rognone
D, Consiglio V, Garetto I, Rizzo L, Veltri A (2013)
stopping therapy, with at least a medium-term
Diffusion-weighted magnetic resonance imag-
outcome, i.e. kidney scars. ing: new perspectives in the diagnostic pathway of
Further studies are clearly needed and many non- complicated acute pyelonephritis. Eur Radiol
mysteries remain to be solved before we fully 23:3077–3086
11. Kim JS, Lee S, Lee KW, Kim JM, Kim YH, Kim
understand this ancient disease.
ME (2014) Relationship between uncommon com-
puted tomography findings and clinical aspects in
patients with acute pyelonephritis. Korean J Urol
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Part II
Imaging of Upper Urinary Tract Infections
Ultrasound of Upper Urinary Tract
Infections 7
Emilio Quaia, Antonio G. Gennari,
and Maria A. Cova
recommend US as a first-line imaging modality Nowadays IVU has increasingly been replaced
also in adults since it is inexpensive, immediate, by computed tomography urography (CTU)
painless, widely available and radiation-free. CT even though there is a paucity of comparative
and MR should be used as a second-line imaging studies between the two techniques [5]. Referring
modality in complicated patients. physician is pleased by the large amount of data
CTU provides not only on UT but also on other
abdominal organs and structures, and patients
7.2.1 Plain Film prefer CTU due to the absence of preparatory
bowel cleansing. Two major drawbacks are costs
Abdominal radiography is a rapid and relatively and radiation dose: CTU undoubtedly costs more
inexpensive examination, so it was used as a part of and exposes patients to a higher dose (10–
the initial examination study in patients with sus- 35 mSv) compared to IVU (5 mSv), but CTU
pected pyelonephritis. However abdominal radiog- data should be critically reviewed on the basis of
raphy had low sensitivity and specificity. Moreover the number of phased used, newest low kilovolt
it became the initial step of every excretory uro- (kV) and milliampere second (mAs) protocol
graphic study, but the successive use of CT over- and automatic tube-current modulation. In con-
came that of plain films in almost all institutions. clusion literature suggests that a dose reduction
The CT scout radiography allows the detection of is feasible technically, but exam protocols should
urinary calcifications and gas but has several draw- be tailored on patient’s characteristics and clini-
backs including the unreliable differentiation of cal problems [5].
abdominal gas from the presence of gas in the UT
and the difficult detection of small urinary calcifi-
cation superimposed on normally calcified struc- 7.2.3 Ultrasonography
tures such as vertebral transverse process [3].
US is an inexpensive, repeatable, widely avail-
able, radiation-free imaging technique, based on
7.2.2 Intravenous Urography properties of acoustic physic. Its widespread use
makes it essential in the initial evaluation of the
Intravenous urography (IVU) had a well- kidneys. Moreover, in urological pathologies, US
established role in the evaluation of the UT; in frequently confirm clinical suspicion or even lead
fact it allows the visualization of the kidneys, to final diagnosis. In US high-frequency ultra-
ureters and bladder after the intravenous injec- sound waves are generated within the probe,
tion of contrast medium. Kidneys contrast where an electric field is applied to an array of
medium removal (filtration) from the blood piezoelectric crystals causing them to vibrate,
stream and excretion in the UT enable the opaci- thus generating ultrasound waves. After being
fication of the structures mentioned above and to generated, waves are sent in the tissues where
image them thanks to several plain films taken at they interact with multiple human body surfaces
predefined image intervals as the contrast flows being attenuated, reflected and/or refracted. The
through the different portions of the UT. The retuned echoes (to the probe) are reconverted to
possible imaging findings in positive IVU were a electrical impulses and generate images. Given
diffuse oedema and an enlargement of the the assumptions of a constant waves’ speed
affected kidneys, a delayed and attenuated within human tissues (1540 m/s) and constant
nephrogram, a retarded filtration and excretion attenuation and waves’ straight path, different
of the contrast medium which determine an echo times are used to characterize (define the
effacement or a delayed filling of the renal col- echogenicity) and localize different tissue types;
lecting system with decreased opacity and a dila- the same assumptions lead also to artefact forma-
tation of the renal collecting system [4]. tion. Ring-down artefact (typical of air presence)
7 Ultrasound of Upper Urinary Tract Infections 59
occurs when US beam encounters fluid, trapped or asking the patient to breathe deeply in order to
within a tetrahedron of air bubbles. It determines rise them up.
a repeated vibration of the air-fliud system creat- The recent widespread use of contrast-
ing a continuous echo transmitted back to the enhanced ultrasonography (CEUS) raised con-
probe. A bright reflector with a continuous bright cern to an otherwise old technique; in fact at first
line extending posteriorly is the way this artefact it was described in 1968. CEUS is based on
is displayed [6]. Shadowing artefact is character- microbubble-based contrast agents (3–10 μm)
ized by a signal void behind a high attenuating composed of a shell of biocompatible materials
zone. In fact when the ultrasound beam encoun- (lipids and proteins) filled with gas (air, perfluo-
ters an area with an extremely higher attenuation, rocarbon or sulphur hexafluoride), each of the
compared to the neighbouring tissues, most of components determine specific physical and
the echoes are reflected, so the echoes returning mechanical properties. Particularly the biocom-
from structures beyond are highly attenuated as patible shell affects their capability to oscillate.
well. Bones and calcified structures such as neph- In CEUS the US beam interacts with microbub-
rolithiasis typically present shadowing [6]. bles in several different ways: at high acoustic
US-Doppler imaging utilizes Doppler effect power, microbubbles are destructed, while at low
(calculating frequency shift) to imagine moving acoustic power, they produce a sound with the
structures, usually blood, within a region of same frequency (f0) of the insonating beam
interest. Structures can be imaged, quantitatively (Fig. 7.1). At their resonant frequency, higher
and qualitatively, as moving towards the probe or than the latter one, a non-linear vibration is pro-
away from it. US-Doppler imaging is helpful in duced, so harmonic (2f0, 3f0, etc.) and subhar-
vessel imaging as well as in the definition of the monic (f0/2, f0/3, etc.) peaks are generated after
vascularization of a specific tissue area. Anyhow the first resonance frequency peak. The mecha-
even US-Doppler imaging has its own artefact. In nism underlying US contrast medium is com-
twinkling artefact, which is typically associated pletely different from other types of contrast
with rough hyperechoic, irregular surfaces, an media; in fact microbubbles are confined within
alternating scintillation of colours on US-Doppler vascular, so they do not pass in the interstice.
imaging is displayed beneath the hyperechoic
structure. It is commonly referred to a form of
intrinsic noise related to the multiple internal
reflections of the incident ultrasound beam on
multiple cracks, which broaden the spectrum.
This phenomenon may aid in detection of renal
calculi.
A proper and detailed US examination of kid-
neys starts with patient in supine position. At first
renal length (longitudinal axis) and cortical thick-
ness should be analysed. Even though normal
right kidney mean longitudinal diameter is
10.74 ± 1.35 cm, and left kidney mean longitudi-
nal diameter is 11.10 ± 1.15 cm, length should be Fig. 7.1 At low acoustic power (10-20 Kilo Pascal)
microbubbles mantains the same radius after compression
related to patient’s height and phenotype. Normal and relaxation so produce a sound with the same fre-
renal anatomy is arranged in an outer echogenic quency of the insonating bram (higher portion of the
cortex, echo-poor pyramids and the sinus. Ribs image). At higher iacoustic power (40-50 Kilo Pascal)
sometimes obscure some portion of kidneys. In microbubbles interact with the US beam expanding and
contracting in a non-linear mode (lower portion of the
such cases the sonographer should find a proper image). Both of these characteristics has been used to
acoustic window locating the probe between ribs obtain CEUS images
60 E. Quaia et al.
Sonoelastography (SE) is an ultrasound tech- and represents a potentially organ- and/or life-
nique to image the relative elastic/mechanical threatening infection. Usually, renal infection is
properties of soft tissue. Tissue could be imaged caused by direct bacterial infection throughout
using strain elastography or shear-wave elastog- two different routes: ascending the UT (most
raphy. In strain elastography tissue is manually common) and via the bloodstream (less com-
compressed with the probe. Speckle tracking is mon). Therefore in ascending pyelonephritis, the
used to image speckle displacement, which is medulla is firstly involved; contrary haematoge-
correlated to tissue displacement. Harder materi- nous spread is first seen as cortical, even though,
als are deformed less, so speckle are more stable, after 48, this distinction is not feasible. Moreover
contrary softer materials are easier to compress in haematogenous spread, both kidneys are typi-
and speckle are displaced more. Shear-wave elas- cally involved. Common pathogens in ascending
tography uses US beam both to compress tissues forms are Escherichia coli and Enterococcus fae-
at a specific depth and to image the propagation calis, two bowel organisms that frequently infect
of shear-wave displacement in the tissue. The US UT. Streptococci and staphylococci are the most
equipment produce a push pulse which compress involved organisms in haematogenous diffusion
parenchyma generating low-frequency waves [7]. In younger patients pyelonephritis is more
(low than 1000 Hz) radiating in a plane perpen- frequent in women [7]. Common symptoms are
dicular to the image plane. Shear waves are then fever, chills, leukocytosis, unilateral or bilateral
imaged using real-time Doppler or time of flight flank pain, dysuria and urinary frequency and
techniques. A specific vendor has also developed urgency. Infrequently gastrointestinal symptoms
an innovative way to image larger tissue portion. may be seen such as abdominal pain, nausea,
Multiple push pulse are sent at different depth vomiting and diarrhoea. Elevated C-reactive pro-
creating a conical wavefront that is used to image tein, elevated erythrocyte sedimentation rate and
mechanical properties of larger sampled areas. leukocytosis with a neutrophilic shift are common
However each technique has its own advantages findings at blood tests. Other typical findings are
and drawbacks. Strain elastography is simpler pyuria, granular or leukocyte casts, bacteriuria
and cheaper, but tissue compression is subjective and positive urinary cultures. Sometimes blood
and deeper organs are difficult to evaluate. cultures and urine cultures share the same bac-
Moreover strain elastography is nonquantitative. teria. If untreated pyelonephritis often leads to
It may only express the ratio of stiffness/elastic- renal scaring, so timely diagnosis and manage-
ity of the pathological portion to the normal one. ment is such important on patients’ outcomes.
Shear-wave elastography does not necessitate At gross pathology involved kidneys are gener-
compression, and it is more quantitative; anyhow ally enlarged and display whitish patchy areas of
quantitative results of different vendors are not varying size alternating to spared parenchyma.
comparable, and renal parenchymal complexity Thin yellow streaks crossing through the medulla
modifies shear-wave propagation. Kidneys have representing collecting ducts filled with pus may
a very complex architecture with a multitude of also be seen [7]. On sectioning, diffuse involve-
tubules parallel to the papilla axis. Shear-wave ment of parenchymal surface by microabscesses
velocity reduces encountering tubules and vascu- may be present [7]. In cases associated with uri-
lar structures thus altering elasticity values. nary obstruction, renal pelvis and calices may be
dilated. Sometimes, severe infection may lead
to papillary necrosis. At microscopy evaluation
7.3 Acute Infection acute bacterial pyelonephritis is characterized by
prominent neutrophilic inflammation of the renal
7.3.1 Pyelonephritis tubules, typically sparring glomeruli and vessels
[7]. There is an associated destruction of tubular
Pyelonephritis is defined as an infection of the basement membranes, resulting in inflammation
renal parenchyma, calyces and renal pelvis spilling into the renal interstitium. Parenchymal
7 Ultrasound of Upper Urinary Tract Infections 61
involvement is often patchy, with alternating ity of choice in acute bacterial pyelonephritis.
areas of intense inflammation and relatively nor- In fact it is superior to US providing detailed
mal-appearing zones [7]. anatomic and physiologic information allowing
Abdominal radiograph is a rapid, inexpen- the definition of both extrarenal and intrarenal
sive examination that was routinely obtained as pathologic conditions. However CEUS is an
the first component of IVU. However the wide- alternative that has been proven to be equally
spread use of CT has overtaken that of radiog- accurate in the detection of acute pyelonephritis
raphy. Moreover the information derived from [9] even though there is a paucity of literature
abdominal radiograph were scarce: urinary tract and EFSUMB 2008 guidelines do not include
gas and calcifications. IVU helped in delineat- complicated pyelonephritis as an indication for
ing the anatomy of the UT and pelvicalyceal CEUS [10]. Parenchymal enhancement after
system. Renal enlargement, striated or delayed microbubble injection is evaluated continuously.
nephrogram, delayed calyceal appearance and Anyhow two major phases could be consid-
dilatation or effacement of the collecting system ered: a cortical phase, in which there is a pro-
were typical findings of acute renal infection. nounced enhancement of the cortex (15–30 s
However only a paucity of patients had abnor- after contrast injection), and a parenchymal
mal IVU findings and there was a low parenchy- phase, in which both the cortex and medullae
mal detail; therefore other imaging techniques enhance (25 s–4 min after contrast injection).
are preferred. Even though US is negative in a Parenchymal phase may also be divided into
vast majority with suspected pyelonephritis, early parenchymal phase (25 s–1 min) and late
it is frequently used as a first-line diagnostic parenchymal phase (after 1 min) [11]. Typical
tool. Interstitial nephritis is not visible on rou- CEUS features of pyelonephritis are a cortical or
tine greyscale images. Positive US findings are corticomedullary focal wedge-shaped or round
renal enlargement, loss of renal sinus fat due to lesion, less enhancing compared to the surround-
oedema, congenital anomalies, hydronephro- ing parenchyma [11] (Fig. 7.2), but CEUS may
sis and modifications in renal echogenicity and also demonstrate normal parenchymal enhance-
corticomedullary differentiation system [3, 8]. ment. However microbubbles are not nephro-
The latter finding could represent haemorrhage toxic so it is safe to use them, even in patients
(hyperechoic), oedema (hypoechoic) or abscess with marginal renal function as a first-line exam.
formation (Fig. 7.2). Colour Doppler improves US elastography has not been used yet to dif-
sensitivity to parenchymal abnormality as most ferentiate areas of nephritis from surrounding
pyelonephritic lesions are ischaemic, and power healthy parenchyma. However infection and
Doppler helps in evaluating of hypoperfused inflammation determine tissue oedema and
areas. Several pitfalls are associated with US urine flow blockage due to tubular obstruction,
kidney evaluation such as differentiations of so renal stiffness increases (Fig. 7.2). Moreover
calcification from intraparenchymal or collect- abscess formation leads to colliquation, so dur-
ing system gas (manifested, respectively, as ing early stages, when abscess cavity is not still
“clean” shadowing and “dirty” shadowing with formed, parenchyma may show reduced tissue
echoes and reverberations) and identification stiffness values compared to nephritis areas.
of perinephric extension of infection system. Even though its clinical utility in acute pyelone-
The urinary bladder should always be imaged phritis is debated, alteration at renal cortex scin-
in a US evaluation for suspected pyelonephri- tigraphy may be seen and may last for at least
tis. Newer applications such as tissue harmonic 3 months after infections. Early scintigraphic
and US contrast agents may enhance sensitivity. findings usually do not predict the late outcome
With tissue harmonic imaging, pyelonephritic [12]. That is why renal cortex scintigraphy is
lesions were commonly seen as focal or segmen- advocate in the detection of post-pyelonephritis
tal, patchy, hypoechoic areas extending from the renal scarring, even though there is no consensus
medulla to the renal capsule [3]. CT is the modal- between authors on the correct timing. Moreover
62 E. Quaia et al.
a b
c d
Fig. 7.2 US findings in a female patient with fever, chills, ing color-Doppler findings (b) are an ischaemic area
and right flank pain in who right kidney pyelonephritis was (arrow). CEUS (c) and SE (d) enhance diagnostic confi-
suspected. A paracoronal US scan (a) showing an enlarged dence confirming that the area has no enhancement (arrow
hyperechoic area (arrow) of parenchyma in which there is in c) after microbubbles injection and is stiffer compared
loss of corticomedullary differentiation. The correspond- to the adjacent renal structures (white box in d)
renal cortical scintigraphy using 99mTc-DMSA ter and the renal pelvis and calices is defined
has proved to be more sensitive than US and IVU hydroureteronephrosis. Pyonephrosis repre-
and as accurate as CT and MRI in the diagnosis sents an infected, obstructed and frequently
of acute pyelonephritis [13]. enlarged, collecting system [3]. Symptoms
are non-specific and similar to those of other
UTI and include fever, chills and flank pain.
7.3.2 Pyonephrosis It should be suspected in patients with known
and Hydronephrosis UT obstruction associated with flank pain and
fever. Early diagnosis is mandatory because
As detailed previously, hydronephrosis, a dis- direct, immediate intervention is crucial. When
tention and dilatation of renal pelvis and caly- pyonephrosis is left untreated, renal func-
ces, caused by an obstruction of the free urine tion deteriorates rapidly and permanently [3].
flow, is a predisposing factor for UTI and per- Moreover patients frequently develop septic
manent renal dysfunction. It may be unilateral shock. Pyonephrosis may be caused by a broad
or bilateral. The distention of both the ure- spectrum of pathologic conditions. Pathogens
7 Ultrasound of Upper Urinary Tract Infections 63
reach the collecting system through ascend- most of the reported cases, with Escherichia coli
ing infection or haematogenous spread. There accounting for 60% [14]. Severely damaged,
are wide predisposing risk factors such as ischaemic kidneys in uncontrolled diabetic
obstruction due to calculi, ureteropelvic junc- patients are the substrate on which pathogenic
tion obstruction, tumours, complications from bacteria form gas causing mixed acid fermenta-
pyelonephritis or strictures and immunosup- tion in a hyperglycaemic environment. The sub-
pression (diabetes, steroids, acquired immuno- sequent evolution is tissue destruction, purulent
deficiency syndrome). infection and inhibition of removal of locally
In the past IVU was an important clinical tool produced gas [14].
in pyonephrosis in the detection of obstructive In about 70% of patients, an abnormal collec-
uropathy. US is valuable in the identification of tion of gas, either mottled gas within the renal
pelvicalyceal system dilatation, echogenic fossa or crescentic collection within the Gerota
debris, fluid-fluid levels within the collecting fascia, could be detected in up to 85% of patients
system and occasionally gas. The presence of [3, 8]. US demonstrates an enlarged kidney with
debris is the most reliable sign of pyonephrosis. hyperechoic nondependent foci within the renal
Furthermore US can detect calculi at the vesico- parenchyma or the collecting system that present
ureteric junction, but the detection of ureteric distal shadowing reverberation. This characteristic
calculi is more challenging [3, 8]. It is thought feature helps in the distinction from renal calculi.
that the evaluation of vascular resistive indices Nevertheless US ability to correctly characterize
ameliorates sensitivity, but there has been pau- EPN is low due to the presence of adjacent bowel
city of studies. Drainage of the infected collect- gas or calculi that may confuse the interpretation.
ing system can be accomplished under CT, US or
fluoroscopic guidance, placing a percutaneous
nephrostomy. Drainage decompresses the col- 7.3.4 Emphysematous Pyelitis
lecting system, allowing better renal plasma flow
and delivery of antibiotics to both parenchyma In emphysematous pyelitis (EP), the presence of
and urine. gas is limited to the renal excretory system. It is a
very rare and benign condition with a low overall
mortality rate as compared to EPN. Thus, it is
7.3.3 Emphysematous mandatory to distinguish between these two enti-
Pyelonephritis ties because of the prognostic differences and dif-
ferent clinical management. As in EPN, also in
Emphysematous pyelonephritis (EPN) refers to EP, gas production in the excretory system is sec-
a unilateral, fulminant, necrotizing, gas forming, ondary to acute bacterial infection [10]. EP is fre-
infection of the renal parenchyma and the peri- quently associated with diabetes mellitus and
nephric tissues [14]. Renal emphysema and obstruction of the UT. The diagnosis is frequently
pneumonephritis are other terms that have been delayed due to the non-specificity of symptoms,
used to describe this condition; contrary emphy- similar to the clinical presentation of uncompli-
sematous pyelitis is the presence of gas in the cated acute pyelonephritis [10].
renal pelvis alone, without parenchymal involve- Abdominal radiography demonstrates gas out-
ment. EPN is a rare and often life-threatening lining the pelvicalyceal system and ureters.
condition that usually occurs in uncontrolled However, abdominal radiography sensitivity is
diabetic patients, more frequently in women [8]. low (33%), due to difficulty in differentiating
Mortality is high, and without early therapeutic renal gas from air in overlying loops of bowel
intervention, the condition generalizes to fulmi- [10]. At US high-amplitude nondependent flat
nant sepsis, and urgent nephrectomy is manda- echoes are typically within the renal sinus or cali-
tory. Escherichia coli, Enterobacter, Klebsiella ces but could be mistaken with calculi or the sur-
pneumoniae and Proteus mirabilis account for rounding intra bowel air.
64 E. Quaia et al.
a b
c d
Fig. 7.3 US (a, b, c) and CT (d) findings in a young nal (c) color-Doppler evaluation, showing the lack of flow
female patient, with known right kidney pyelonephritis, signal in the mass (arrow). Axial contrast enhanced CT
irresponsive to antibiotic treatment. A para-axial US scan scan at nephroparenchymal phase confirms (arrow) the
demonstrating a bulky hypoechoic mass (arrow) arising presence of an abscess, revealing a hypodense area (*)
from the right renal parenchyma protruding within the fat delimited by a hyperdense rim, and the involvement of the
tissue of perirenal space. A para-axial (b) and a paracoro- surrounding fat tissue
7 Ultrasound of Upper Urinary Tract Infections 65
suggestive of air, may also be seen. Debris are eral typical imaging findings: renal scarring,
movable with patient decubitus. Loculation and atrophy and cortical thinning, hypertrophy of
septations are other possible imaging findings. sparred renal parenchyma, thickening and dila-
Typically there is no internal flow on colour tation of calyceal system and renal asymmetry.
Doppler images [3, 8]. At CEUS abscesses pres- On US scars are linear hyperechoic areas per-
ent as rounded or geographical areas lacking of pendicular to kidney’s surface [8]. Focal areas
enhancement throughout the whole exam. Some of fibrosis and cortical thinning may also be rec-
present with rim enhancement or enhancing thick ognized as well as an increased echogenicity of
septa [11]. Moreover, US- and CT-guided renal pelvis due to an increased renal sinus fat
percutaneous placement of drains helps most of [8]. Moreover a dilatation of calices and the
the patients to improve clinical status and is entire collecting system may be seen due to
sometimes a definitive procedure [8]. parenchymal fibrosis [8].
kidneys are usually enlarged with single or ings [3]. IVU demonstrates a markedly decreased
multiple yellow to orange nodules, abscess, renal function with an extremely retarded or absent
cortical scarring and atrophy and involvement excretion of contrast medium even at delayed
of perinephric fat [15]. As detailed before in imaging. US findings in diffuse XGP demonstrate
the microscopic evaluation, the inflammatory an enlarged kidney, with a loss of the typical archi-
infiltrate mainly composed of xanthomatous tecture and a large amorphous central echogenicity
cells, which have a foamy cytoplasm with an that corresponds to the staghorn calculus which
abundant clear to vacuolated cytoplasm and are generally is associated with acoustic shadowing
consistent with histiocytes, is mixed with fibro- [3, 15]. Contrary there are no specific US imaging
sis and cholesterol clefts. The parenchyma features in focal XGP; in fact it is impossible to
nearby is characterized by calyceal mucosa differentiate it from a renal abscess.
ulceration, necrotic debris and tubular
atrophy.
A large staghorn is commonly depicted in 7.4.3 Tubercular Infection
most, but not all, cases at abdominal radiographs
even though it is a non-specific sign (Fig. 7.4). The genitourinary system involvement in patients
Renal contour enlargement and loss of the ipsilat- with extrapulmonary tuberculosis is well known
eral psoas margin are additional radiographic find- and accounts for 15–20% of patients. The cor-
a b
Fig. 7.4 Plain film (a), US (b) and CT (c) of a young the presence of a large, hyperechoic, staghorn calculus
man with fever and abdominal pain; he suffered of severe within the right collecting system, which produced acous-
perinatal brain hypoxia. Large bilateral calculi (arrows) tic shadowing underneath. A subsequent CT scan was
were identified at abdominal X-ray. The one on the right acquired (c) which ruled out the presence of XGP, demon-
side had staghorn conformation. Abdominal US (b) exam- strating acute cholecystitis (not shown), but better imaged
ination performed to rule out presence of XGP confirmed the staghorn calculus
7 Ultrasound of Upper Urinary Tract Infections 67
relation with pulmonary tuberculosis is debated defined as the “great imitator”. But nevertheless
in literature: some claim a relation between the the presence of several abnormalities at the same
two with a delay between pulmonary and geni- time allows the correct diagnosis [4].
tourinary disease that varies from 5 to 40 years Several different types of calcifications may
[8, 16], while other suggests that less than 50% be seen at abdominal radiographs including
of patients with urinary tuberculosis actually amorphous, speckled or curvilinear patterns,
have abnormal results from chest radiography “putty kidney” (calcified thick material filling a
[3]. Symptoms are non-specific and range from dilated collecting system) and calcium in paren-
fever, weight loss and fatigue, which are less chymal mass and lobar calcifications [8].
common to dysuria, increased frequency of mic- Calcifications are present in 24–44% of patients
turition and microscopic or macroscopic haema- with UT tuberculosis [16]. Common findings on
turia associated with back, abdominal or flank IVU include focal scars, dystrophic parenchymal
pain. Also, purified protein derivative skin testing calcifications, cavitary lesions and infundibular
is inconclusive in 20% of patients, and cultures stenosis which lead to focal or generalized hydro-
of urine from affected patients may be distorted nephrosis [8]. Ureteral ulceration, wall thicken-
or confounded by the simultaneous presence of ing and focal dilatation determine a sawtooth- or
more common urinary pathogens yielding to a corkscrew-like aspect of the ureter; the subse-
difficult diagnosis. quent progressive fibrosis determines a straighter
Renal involvement is related to haematoge- and more fixed appearance of the ureter, an aspect
nous spread of mycobacterium tuberculosis, and that is normally defined as “pipestem ureter” [8].
even though dissemination is possible bilaterally, Even though US has limited use in the definition
clinical involvement is usually prominent on one of urinary tuberculosis, two patterns have been
side. The high oxygen tension and blood flow in described: an infiltrating one with higher echo-
glomeruli and peritubular capillary beds deter- genicity related to the presence of calcifications
mine an excellent environment for bacteria and an hydronephrotic or pyonephrotic one with
development and proliferation [16]. Initially dilated calices and a renal pelvis with reduced
small cortical granulomas, nearby glomeruli, dimensions.
form when host immunity prevails and disease
lasts dormant for decades [3, 8, 16]. The further
compromission of immune system leads granulo- 7.4.4 Human Immunodeficiency
mas to enlarge and coalesce. With ruptured capil- Virus Relate Infections
lary bacteria gain access to proximal tubules and and Nephropathy
loops of Henle creating caseating granuloma and
papillary necrosis [3, 16]. Further extension in Despite the prevention programme and their
the collecting system often occurs, which gener- impact in controlling human immunodeficiency
ates fibrosis [3]. Moreover, if left untreated, sub- virus (HIV) spreading in population of some
sequent evolution of the disease determines a loss countries, the HIV-acquired immunodeficiency
of renal function and may spread to retroperito- syndrome (AIDS) epidemic continues to grow,
neal organs including the colon [3]. In fact, the and by 2005 there were more than 40 million
involvement of the ureter and bladder is second- people infected worldwide [17]. Even though
ary to renal involvement. Granuloma formation respiratory, neurologic and gastrointestinal
within the transitional epithelium could lead to involvement and imaging characteristics have
fibrosis, thus to ureteral strictures and ureteral been widely described, there is a lower definition
shortening and calcification [8]. It is important to of HIV renal and UT involvement and its imag-
specify that there is no specific imaging clue for ing aspects. There are several different causes
the diagnosis of urinary tuberculosis since simi- attributed to renal impairment in HIV patients:
lar imaging findings could be caused by several HIV acquired nephropathy, opportunistic infec-
other pathogens; that is the reason why it is tions, drug-related renal disease (especially in
68 E. Quaia et al.
patients treated with HAART antiviral therapy), rosis is seen. As the disease evolves, glomeruli
neoplasia and vascular causes [17]. The disease- evolve in a tight solidified ball crowded by overly-
related reduction in T-helper lymphocytes cells ing enlarged, vacuolated visceral epithelial cells
and the subsequent immunosuppression make [19]. In addition to glomeruli modifications also,
AIDS patients highly susceptible of opportunistic tubular involvement is present with atrophy, inter-
fungal infections, such as Pneumocystis jirovecii, stitial fibrosis, oedema, inflammation and wide-
although P. jirovecii most frequently infects lung, spread tubular degenerative and regenerative
haematogenous and lymphatic spread occur in changes which determine distended tubules con-
1% of patients [17]. Histological evaluation of taining loose proteinaceous casts to form tubular
kidneys infected with P. jirovecii demonstrated microcysts [19].
multiple calcific nodules particularly in renal cor- At US kidneys appear as normal size or
tex, representing areas of pathogen infiltration enlarged. The initial enlargement is on axial
and consequent destruction of renal tubules [17]. dimension with kidneys losing their normal
Focal areas of increased echogenicity have aspect and gaining a bulbous shape. A high
been described in the renal cortex and medulla echogenic parenchyma is the most characteris-
[18] but also in the liver, spleen, pancreas and tic feature, with a loss of differentiation
adrenal gland. At CT evaluation calcification was between fat renal sinus and renal cortex which
described in the renal cortex [17]. However all have to be related with parenchymal disease
these findings were non-specific for the diagnosis [17]. Moreover the reduction of renal sinus
of P. jirovecii infection and in fact were subse- dimensions due to renal oedema has been
quently described also in Mycobacterium avium described in up to 49% of patients. Also a
infection and Cytomegalovirus. thickening of pelvicalyceal system has also
Other fungal infections associated with AIDS been described both at US and CT [17].
are Candida albicans and Aspergillus infection.
They can manifest as the presence of several
focal microabscess in the kidney parenchyma 7.4.5 Malakoplakia
and hydronephrosis. At histologic analysis, kid-
neys contain a combination of fungal spores, Malakoplakia is a rare granulomatous condition
hyphae and pseudohyphae [17]. first reported by Michaelis and Gutmann in 1902,
HIV-acquired nephropathy is a relatively new characterized histopathologically by von
disease (the first published description was in Hansemann histiocytes and Michaelis-Gutmann
1984) recognized as a complication of HIV infec- bodies. Von Hansemann cells are large ovoid
tions. HIV viruses directly infect renal epithelial eosinophilic macrophages with intracytoplasmic
cells and led to direct expression of HIV genes bodies, the Michaelis-Gutmann bodies [20]. The
within those cells. It is characterized by progressive aetiology is unknown; it is believed to be associ-
renal failure often associated with proteinuria and ated with defective bacterial digestion due to
bland urinary sediment and has a mortality rate of impaired macrophage function [20]. It can pres-
100% within 6 months from the onset of uraemia ent in several different ways; moreover since it
[8, 19]. HIV-related nephropathy is more frequent can occur in almost any part of the body, symp-
in patients with a CD4 cell count <200 cells/mm3. toms depend on the organ involved, thus present-
On gross specimen evaluation at autopsy, the kid- ing a huge diagnostic challenge. Anyhow
neys were pale, swollen and enlarged due to the malakoplakia is most commonly found in the
presence of several tubular microcyst distending genitourinary tract [20]. The incidence rate is
the parenchyma [19]. Even though imaging could three to four times higher in middle-aged female
help in the diagnostic workup of patients, an in vivo who develop malakoplakia than their male coun-
diagnosis is only achieved with renal biopsy. At terparts. The most frequently recovered organism
microscopic evaluation in the acute setting a severe in urine culture and upon flexible cystoscopy is
form of collapsing focal segmental glomeruloscle- Escherichia coli [16]. Moreover malakoplakia is
7 Ultrasound of Upper Urinary Tract Infections 69
phrosis. Surprisingly renal function in early stages asymptomatic for several years. Most common
of the disease is preserved; contrary chronic com- symptoms are flank mass, pain and dysuria [25].
pression is associated with parenchymal damage Renal hydatid cysts are more frequently unilat-
and renal failure [24]. eral, solitary and localized in the cortex of the
Due to the specific involvement of the bladder, superior or inferior pole. A severe, but uncom-
imaging findings mirror the pathologic course. mon (18%), complication is the rupture of the
Acute phase is characterized by nodular bladder cysts in the collecting system with resultant renal
wall thickening at IVU or CTU. End-stage schis- colic and hydatiduria [25].
tosomiasis leads to bladder wall thickening, con- Abdominal radiography images a soft tissue
traction and calcification; the latter is easily seen mass that corresponds to the cyst. In a minority of
at plain radiograph. Calcifications are typically cases, curvilinear or ring-shaped calcifications
linear or curvilinear. Ureter involvement is rare may be seen. IVU demonstrates infundibular and
and typically limited to the lower third. Findings calyceal distortion [25]. US appearance of renal
in the affected part are the same described for the hydatid cysts may vary between a unilocular sim-
bladder walls. Fibrosis of the lower third ureters ple renal cyst and multiseptated daughter cysts.
produces a partial urine obstruction. Upper parts Three signs raise suspicion on a cyst: a thick,
of ureters initially compensate by dilatation bilayered wall, the “falling snowflake” which is
hypertrophy that generates enough pressure to the presence of multiple echogenic foci produced
overcome distal obstruction. IVU and CTU may by hydatid sand that modify their locations as the
demonstrate ureteral calcifications and stenosis, patients change position and a “floating mem-
ureterectasis and obstructive uropathy. brane” that represents the detachment of the
Hydatid disease is a zoonosis caused by endocyst from the pericyst [25].
Echinococcus granulosus’ larvae. It is endemic
in many regions of the world including the
Mediterranean, Africa, South America, Australia, References
Middle East and New Zealand [25]. Sheep, cattle
and camels are the common intermediate hosts 1. Hooton T (2012) Uncomplicated urinary tract infec-
for this worm. The worm’s eggs are passed in tion. N Engl J Med 366:1028–1037
2. Solomon CG, Schaeffer AJ, Nicolle LE (2016)
stool and are transmitted to humans by dogs [23].
Urinary tract infections in older men. N Engl J
Larvae escape from eggs and penetrate the human Med 374(6):562–571. https://doi.org/10.1056/
body throughout the intestinal mucosa. From NEJMcp1503950
there they spread in the portal circulation. Even 3. Craig WD, Wagner BJ, Travis MD (2008) From the
archives of the AFIP: pyelonephritis: radiologic-
though the majority of larvae are filtered by the
pathologic review. Radiographics 28:255–276
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eral circulation and involve other organs, such as of he kidney, 2nd edn. Springer, Heidelberg
the kidneys [23]. The undestroyed larvae form 5. Stacul F, Rossi A, Cova MA (2008) CT urography: the
end of IVU? Radiol Med 113(5):658–669
cysts. The wall of hydatid cyst is formed by three
6. Feldman MK (2009) US artifacts 1. Radiographics
layers: the outermost (pericystic) is produced by 29(4):1179–1189
modified host cell that forms in the presence of 7. Hou J, Herlitz LC (2014) Renal infections. Surg
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8. Browne RFJ, Zwirewich C, Torreggiani WC (2004)
acellular, membrane that allows the passage of
Imaging of urinary tract infection in the adult. Eur
nutrients; and the inner is where the laminated Radiol Suppl 14(3):168–183
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fluid is a clear transudate that is antigenic if (2008) Acute pyelonephritis: comparison of diagno-
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released into the host’s body as a consequence of
ultrasonography. BJU Int 101(3):341–344
cyst rupture causing severe reactions and anaphy- 10. Roy C, Pfleger DD, Tuchmann CM, Lang HH, Saussine
laxis. Of all human organs, renal involvement is CC, Jacqmin D (2001) Emphysematous pyelitis: find-
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11. Fontanilla T, Minaya J, Corteás C et al (2012) Acute 18. Kay CJ (1992) Renal diseases in patients with
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therapy. Semin. Nephrol. 28(6):513–522
(2011) Candida urinary tract infections - diagnosis. 20. Dong H, Dawes S, Philip J, Chaudhri S, Subramonian
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Radiographics 28(5):1339–1354 ease. Radiographics 30(2):334–337
Cross-Sectional Imaging of Acute
Pyeloureteritis and Pyonephrosis 8
Massimo Tonolini
and coronal planes: the latter provide a panoramic incidentally encountered in patients with unrelated
representation the renal and excretory structures clinical features: in this situation, the aware radi-
and easily allow assessment of renal length, con- ologist provides the first indication of the presence
tours and parenchymal enhancement. Image read- of an active UTI. APU may be observed in the
ing using narrow CT window settings may allow context of acute pyelonephritis (APN) or cystitis;
an improved identification of perinephric fat alternatively, it may represent the only feature sug-
changes and of subtle renal hypoenhancing regions gesting an ongoing ascending UTI, before charac-
[7–13]. teristic renal changes of APN appear. Therefore
early CT diagnosis allows preventing further dis-
ease progression [8, 12, 14–16].
8.2 Acute Pyeloureteritis AT CT, infectious APU is heralded by dif-
fuse, mild or moderate circumferential pelvi-
Due to the widespread use of multidetector CT, calyceal and/or ureteral mural thickening
acute pyeloureteritis (APU) currently represents a (≥2 mm) with uniform, more or less prominent
not uncommon finding in cross-sectional studies contrast enhancement corresponding to urothe-
performed to investigate haematuria, flank pain or lial inflammation; inflammatory stranding of
suspected urinary tract infection (UTI). Moreover, the peripelvic and periureteral fat is commonly
its characteristic imaging signs are sometimes associated (Figs. 8.1, 8.2, 8.3, and 8.4). These
a b c
d e f
Fig. 8.1 A 59-year-old female with chronic HIV and solitary right kidney and urolithiasis was investigated
hepatitis C virus coinfection was hospitalized because of with multidetector CT (d–f) after retrograde ureteroscopy
low-grade fever, lumbar pain, dysuria and urinary inconti- and stent (thick arrows) positioning. The thin, hyperen-
nence. Multiplanar images from contrast-enhanced CT hancing mural thickening (thin arrows) was best percep-
(a–c) showed mild, uniform, diffusely enhancing pelvi- tible in corticomedullary (d) and nephrographic (e) phase
calyceal mural thickening (thin arrows) as the only sign of images and obscured in the delayed excretory phase (f).
active urinary tract infection (UTI) from multiresistant Note normal renal parenchymal enhancement and func-
Escherichia coli; the same finding was absent on the tion, calyceal stone at lower renal pole in (d)
contralateral collecting system. A 69-year-old male with
8 Cross-Sectional Imaging of Acute Pyeloureteritis and Pyonephrosis 75
a b c
d e
Fig. 8.2 A 59-year-old female suffered from postproce- tion reconstruction) acquisition phases. With normal renal
dural fever after left-sided ureteral stenting (thick arrows) function on both sides, the left renal pelvis showed mild-
to relieve pyeloureteral junction syndrome and underwent enhancing mural thickening (thin arrows) and subtle
CT including unenhanced (a), nephrographic (b, c) and inflammatory stranding of the peripelvic fat (*)
delayed excretory (d, e with maximum intensity projec-
CT appearances are often relatively subtle, urography techniques which provide combined
best perceptible in comparison with the unaf- nephrographic and excretory imaging in a single
fected contralateral side, by far most conspicu- acquisition [15, 17, 18].
ous in the nephrographic phase of enhancement, The CT differential diagnosis of APU encom-
and potentially reversible with successful passes tuberculosis, primary urothelial malignan-
treatment of UTI (Fig. 8.3). Occasionally, the cies, ureteral metastases and other uncommon
presence of air within the collecting system or conditions such as ureteritis cystica, amyloidosis
ureter (Fig. 8.5) without previous instrumenta- and periureteral haematoma (Fig. 8.6). The key
tion or surgery indicates UTI by gas-forming consideration is that APU does not narrow nor
bacteria [8, 12, 14–16]. obstruct the renal pelvis and ureter. Conversely,
Conversely, CT signs consistent with APU are the identification of focal, asymmetric or mass-
often obscured in the excretory phase because of forming mural thickening and of filling defects
the decreased mural enhancement and the adja- protruding in the renal pelvis or ureteral lumen
cent high-attenuation-enhanced urine. This is suggests an underlying malignant process, most
true not only for the usual multiphasic CT studies usually transitional cell carcinoma (Fig. 8.7). As
including preliminary unenhanced, corticome- discussed in the dedicated chapter of this book,
dullary, nephrographic and delayed phases but urinary tuberculosis results from haematogenous
also for the modern dual or triple split-bolus CT spread and often involves the ureters with
76 M. Tonolini
a b c
d e f
Fig. 8.3 A 49-year-old woman with demyelinating dis- contralateral side, which extended along the ureter and
ease suffered from diffuse abdominal pain, emesis and was consistent with an acute ascending UTI without signs
irritative voiding symptoms, without fever. Contrast- of pyelonephritis. Urine cultures disclosed infection from
enhanced multidetector CT (a–d) showed normal, sym- multiple Gram-negative bacteria. After prompt clinical
metric size, parenchymal thickness and enhancement of and laboratory improvement on antibiotic therapy,
both kidneys. On the right side, some perinephric and repeated CT (Fig. e, f) depicted regression of perinephric
pararenal fluid (*) was present. The ipsilateral renal pelvis changes and of pyeloureteritis (Adapted with permission
showed mild, circumferential mural thickening with uro- from Ref.no. [21])
thelial hyperenhancement (thin arrows) compared to the
a b c
Fig. 8.4 A 44-year-old male had history long-standing hydronephrosis compared to previous studies (not shown)
HIV infection on antiretroviral treatment, known left- with parenchymal thinning and appearance of urothelial
sided hydronephrosis and previously resected nephro- enhancement (thin arrows) and of marked periureteral
genic adenoma of the urinary bladder. Currently suffering stranding. The patient’s clinical conditions and laboratory
from fever and macroscopic haematuria, he underwent changes improved after ureteral stenting
contrast-enhanced CT (a–c) which showed worsening
8 Cross-Sectional Imaging of Acute Pyeloureteritis and Pyonephrosis 77
a b c
Fig. 8.5 A 34-year-old female suffered from recurrent arrows in a, b) in the right ureter, with minimally thick-
UTIs after caesarean section a few months earlier. After ened walls and inhomogeneous perfusion at the upper
inconclusive sonography and without previous instrumen- third of the contralateral kidney (c)
tation, contrast-enhanced CT showed some air (thin
a b
c d
Fig. 8.6 Following percutaneous nephrolithotomy (PCNL) and posterior pararenal spaces (arrowhead in a). CT urogra-
treatment performed to treat a 2-cm left renal pelvis stone, phy (c, d) showed functioning left kidney with a 2-cm
a 46-year-old woman was not discharged because of pro- devascularized injury (arrow in c) at the dorsal middle third
gressive, asymptomatic haemoglobin drop (nadir 8.4 g/dL). and hypodense suburothelial haemorrhage (thin arrows)
Four days later, unenhanced CT showed ureteral stent compared to the well-opacified pyeloureteral lumen.
(thick arrows) in place, hyperattenuating (50 HU) circum- Conservative management including blood transfusions
ferential mural thickening of the renal pelvis and proximal allowed hospital discharge in a few days, normalization of
ureter (thin arrows in a, b) consistent with suburothelial clinical, biochemistry and imaging abnormalities within a
haemorrhage and minimal blood in the ipsilateral perirenal month (Reproduced from Open Access Ref. no. [22])
78 M. Tonolini
a b
c d
Fig. 8.7 In a 60-year-old male undergoing follow-up for arrows) showed higher-than-water precontrast attenuation
resected colon cancer, multidetector CT (a–d) showed (b) with homogeneous mural enhancement and strictured
first-degree hydronephrosis (+) with delayed nephrogram lumen, corresponding to metachronous transitional cell
on the left side (a). The ipsilateral lumbar ureter (thin carcinoma
“ragged” irregular mural thickening, ureteral fill- superimposed infection. Clinically, patients with
ing defects, calcification and strictures [14, 15]. pyonephrosis generally present with the usual signs
and symptoms of UTI, but more subtle manifesta-
tions such as low-grade fever, malaise, weight loss
8.3 Pyonephrosis and dull pain are not uncommon: it has been
reported that as many as 15% of patients are afe-
In the context of UTI, hydronephrosis represents a brile. Practically, pyonephrosis should be suspected
key finding, which requires early diagnosis and in any patient with urinary tract obstruction and
immediate treatment. Pyonephrosis, defined by an accompanying fever and flank pain. As discussed
infected and obstructed collecting system, repre- in the interventional radiology chapters of this
sents a true urological emergency: if left untreated, book, prompt decompression of pyonephrosis
it is associated with impending risk of sepsis and should be performed by means of percutaneous
rapid and permanent loss of renal function. In the nephrostomy or ureteral stenting, to relieve obstruc-
adult population, pyonephrosis may result from tion and also to confirm the diagnosis [8, 12, 19].
either acute or chronic obstruction from lithiasis, Radiologists should maintain a high level of
tumours, strictures or congenital anomalies with suspicion, since imaging differentiation of pyo-
8 Cross-Sectional Imaging of Acute Pyeloureteritis and Pyonephrosis 79
a b c
d e f
Fig. 8.8 A 40-year-old female experienced septic fever (not shown). Clinical and imaging suspicion of pyone-
3 days after a PCNL treatment. Unenhanced (a) and phrosis was confirmed and relieved by positioning of ure-
contrast-enhanced (b, c) images showed left-sided pelvi- teral stent plus intensive antibiotic therapy (Adapted from
calyceal dilatation with inflammatory-type stranding of Open Access Ref. no. [22]). Analogous pre- (d) and post-
the surrounding fat (*), mild-enhancing urothelial thick- contrast (e, f) CT signs were present in a 53-year-old
ening (thin arrow in b), ipsilateral fascial effusion (arrows) female with history of psychiatric disease and acute lum-
and decreased nephrographic parenchymal enhancement bar pain, consistent with superimposed UTI on pre-
compared to the contralateral kidney. Hydronephrosis was existent pyeloureteral junction stricture, which was
due to small residual stone fragments in the lumbar ureter relieved by long-term ureteral stenting
80 M. Tonolini
a b
c d
Fig. 8.9 An elderly female with septic fever and abdomi- (§) in post-contrast images (b and c). Note calcific caly-
nal pain had CT diagnosis of severe right-sided hydrone- ceal lithiasis in a. The picture resolved after percutaneous
phrosis (+) with associated perinephric fat stranding (on drainage of psoas abscess and nephrostomy (thick arrow
unenhanced image a), hyperenhancing pyelic wall (thin in follow-up CT d)
arrow), fascial effusion (arrows) and psoas muscle abscess
a b c
Fig. 8.10 A 78-year-old overweight male suffered from marked perinephric fat stranding (*) and fascial fluid
acute right flank pain. Unenhanced CT (urolithiasis proto- (arrows) and first-degree hydronephrosis caused by a
col, a–c) showed mild thickening of the renal parenchyma, 6-mm stone (arrowhead in c) of the pyeloureteral junction
8 Cross-Sectional Imaging of Acute Pyeloureteritis and Pyonephrosis 81
a b
c d
Fig. 8.11 In a 49-year-old male suffering from acute left hydronephrosis (+) with associated delayed nephrogram
renal colic, urgent unenhanced CT (a) detected a small- (b) compared to the contralateral kidney, preserved con-
sized calculus (arrowhead) of the distal ureter. The attend- trast excretion (c, d) and persistent ureteral calculus
ing urologist requested study completion with intravenous (arrowhead in d), without signs of UTI
contrast (b–d), which confirmed ipsilateral first-degree
cause, most commonly a ureteral stone (Figs. 8.10 with calculation of apparent diffusion coeffi-
and 8.11) [8, 11–13, 19]. cients (ADC) is highly reliable in the differentia-
Although seldom used, MRI consistently tion between hydronephroses from pyonephrosis
depicts the urine-filled collecting system by the (Fig. 8.12): the infected pelvicalyceal system
use of static-fluid MR urography techniques. In appears markedly hyperintense on high b-value
pyonephrosis, dependent debris and fluid-fluid DWI images, with corresponding very low
levels may be seen within the dilated urine- (0.64 ± 0.35 × 10−3 mm2/s) ADC values com-
filled cavities. Furthermore, increasing reports pared to 2.98 ± 0.65 × 10−3 mm2/s of noninfected
describe that the use of diffusion-weighted MRI urine [19, 20].
82 M. Tonolini
a b c
d e f
Fig. 8.12 In a 68-year-old male with previous radical normal low signal (*). Corresponding apparent diffusion
cystectomy with ileal conduit (Bricker’s technique), fat- coefficient (ADC) maps (d, e) showed hypointensity from
suppressed T2-weighted MR image (a) showed enlarged low ADC values in infected (+) compared to noninfected
right kidney with perinephric fluid (arrows) and hydrone- urine (*). Excretory-phase T1-weighted acquisition after
phrosis (+) characterized by different signal intensity of intravenous gadolinium contrast (f) showed lack of uri-
urine compared to the contralateral renal pelvis (*). nary opacification in the right-sided dilated urinary cavi-
Diffusion-weighted images (b value 700) showed visually ties. Pyonephrosis ultimately resolved after 2 months of
high signal (+) of urine in the dilated right collecting sys- intensive antibiotic therapy (Courtesy of dr. D.Gned,
tem consistent with pyonephrosis, forming a fluid-fluid Hospital “San Luigi Gonzaga”, Orbassano—Italy)
level (in c) with the nondependent, noninfected urine with
12. Stunell H, Buckley O, Feeney J et al (2007) Imaging s hop--protocol design, opacification, and image qual-
of acute pyelonephritis in the adult. Eur Radiol ity analysis. Radiology 255:508–516
17:1820–1828 18. Van Der Molen AJ, Cowan NC, Mueller-Lisse UG
13. Demertzis J, Menias CO (2007) State of the art: et al (2008) CT urography: definition, indications
imaging of renal infections. Emerg Radiol 14: and techniques. A guideline for clinical practice. Eur
13–22 Radiol 18:4–17
14. Wasnik AP, Elsayes KM, Kaza RK et al (2011)
19. Das CJ, Ahmad Z, Sharma S et al (2014) Multimodality
Multimodality imaging in ureteric and periureteric imaging of renal inflammatory lesions. World J Radiol
pathologic abnormalities. AJR Am J Roentgenol 6:865–873
197:W1083–W1092 20. Chan JH, Tsui EY, Luk SH et al (2001) MR diffusion-
15. Potenta SE, D’Agostino R, Sternberg K et al
weighted imaging of kidney: differentiation between
(2015) CT urography for evaluation of the ureter. hydronephrosis and pyonephrosis. Clin Imaging
Radiographics 35:709–726 25:110–113
16. Uyeda JW, Gans BS, Sodickson A (2015) Imaging of 21. Tonolini M (2013) Acute pyelo-ureteritis: MDCT
acute and emergent genitourinary conditions: what diagnosis and follow-up {Online}. EuroRAD URL:
the radiologist needs to know. AJR Am J Roentgenol http://www.eurorad.org/case.php?id=10764
204:W631–W639 22. Tonolini M, Villa F, Ippolito S et al (2014) Cross-
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(2010) Kidney and urinary tract imaging: triple- extracorporeal and endourological treatment of uro-
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CT Imaging and Differential
Diagnosis of Acute Pyelonephritis 9
Adriana Vella and Massimo Tonolini
a b c
Fig. 9.1 Early acute pyelonephritis (APN) with “striated hypoattenuating “streaks” (arrows) oriented perpendicu-
nephrogram” appearance and common accessory signs in larly to the cortex, best visualized in detail image (a).
a 32-year-old female suffering from acute abdominal pain Accessory signs consistent with APN included mild
with clinical and laboratory signs of sepsis. Nephrographic hyperenhancing pyeloureteral thickening (thin arrows),
phase images from contrast-enhanced CT show left kid- ipsilateral perinephric fat stranding (*) and pronounced
ney with upper normal limit size and parenchymal thick- gallbladder mural oedema (thick arrows in b, c)
ness, mildly inhomogeneous perfusion with thin
a b c
Fig. 9.2 Unilateral APN in a 49-year-old female with ing intraparenchymal focus (arrow) at the upper third of
characteristic clinical manifestations and laboratory signs the left kidney. The presence and extent of focal APN is
consistent with urinary tract infection (UTI). best assessed using modified CT window settings (b) and
Nephrographic phase CT viewed at standard abdominal coronal image review (c). Infection was confirmed by
window settings (a) showed a circumscribed hypoenhanc- associated CT finding of ipsilateral pyelitis (not shown)
9 CT Imaging and Differential Diagnosis of Acute Pyelonephritis 87
a b c
Fig. 9.3 Unilateral APN in a 50-year-old HIV-positive (arrows in a, b) measuring approximately 2.5 cm in maxi-
female with fever, flank pain and increased acute phase mum diameter at the upper third of right kidney. Infection
reactants. Unfortunately acquired in a corticomedullary was confirmed by associated CT finding of ipsilateral
phase, contrast-enhanced images detected an ill-defined pyelitis (thin arrow in c)
intraparenchymal focus of inhomogeneous perfusion
a b c
Fig. 9.4 A 70-year-old male experienced septic fever consistent with clinical diagnosis of acute UTI. Repeated
3 months after radical cystectomy with orthotopic neo- nephrographic phase CT (c) during antibiotic therapy
bladder reconstruction (not shown). Multidetector CT showed persistence of an APN focus at the upper pole
urography (a, b) detected at least two faintly hypoenhanc- (arrow), which ultimately regressed at further follow-up
ing intraparenchymal foci (arrows) in the right kidney (not shown)
a b c
Fig. 9.5 Unilateral APN in a young 20-year-old female contrast CT (b, c) confirmed a solitary hypoenhancing
with fever and flank pain. Initially, ultrasound (a) detected renal focus (arrows) without abscessualization and peri-
a focal area of increased parenchymal echogenicity at the nephric extension, thus allowing appropriate treatment
upper third of right kidney (+). Nephrographic phase post- choice
a b c
Fig. 9.6 Characteristic appearance of multifocal unilateral (a–c) showed multiple hypoenhancing bands orthogonal to
APN in a 53-year-old female with fever and lower right the renal cortex (arrows) throughout the normal-sized right
quadrant pain. CT was requested to differentiate acute kidney, with associated ipsilateral mild hyperenhancing
appendicitis from APN. Nephrographic phase CT images pyeloureteral thickening (thin arrows in b, c)
9 CT Imaging and Differential Diagnosis of Acute Pyelonephritis 89
a b
c d
Fig. 9.7 Usual appearance of multifocal unilateral APN fascia. Ten weeks later, repeated CT (c, d) after antibiotic
in a 51-year-old female with abdominal pain and hyper- treatment showed regression of APN changes, with devel-
leukocytosis. Initial CT (a, b) showed at least four wedge- opment of multiple contour changes and cortical irregu-
shaped hypoenhancing parenchymal regions in the left larities consistent with early scarring
kidney (arrows) plus minimal thickening of ipsilateral
ment (Figs. 9.1, 9.3, and 9.6) as extensively (d) Hepatic “mosaic” reticular enhancement pat-
described in the previous chapter. tern in the arterial-dominant or portal venous
(b) Ipsilateral perinephric fat stranding and/or
phases, with complete homogenization on
thickening of Gerota’s fascia (Figs. 9.1, 9.3, delayed phase: this appearance has been
9.4, 9.7, 9.8, and 9.9), which may be also recently described in patients with acute extra-
present in acute obstruction, urinoma or hepatic infectious or inflammatory disorders
other inflammatory conditions such as acute including APN, reflects sepsis-associated liver
pancreatitis [14]. dysfunction and corresponds histologically to
(c) Periportal fluid “tracking” and gallbladder liver sinusoidal dilatation and is reversible in
oedema (Fig. 9.1) which should not be con- 82% of cases at follow-up after resolution of
fused with cholecystitis. the underlying disorders [15, 16].
90 A. Vella and M. Tonolini
a b c
Fig. 9.8 Mild, bilateral APN in a 54-year-old female with history of urolithiasis, suffering from culture-proven UTI. At
CT (a–c) both kidneys showed small-sized hypoenhancing bands (arrows). Note lower pole calculus (thick arrow in c)
a b c
d e f
Fig. 9.9 Urinary sepsis from Escherichia coli APN in a biotics, a week later MRI showed tiny bilateral foci of
49-year-old male. Initial CT (a–c) showed multiple ill- restricted diffusion (thin arrows in b 800 diffusion-
defined cortical hypoenhancing foci (arrows) in both kid- weighted image d) and subtle hypoenhancing parenchy-
neys, consistent with haematogenous dissemination of mal regions (arrows in post-gadolinium T1-weighted
infection. After prompt improvement on intravenous anti- images e and f)
9 CT Imaging and Differential Diagnosis of Acute Pyelonephritis 91
(e) Lung base effusions, particularly if ipsilat- demarcated by a thin rim-like enhancing capsule
eral [4, 5, 7–10, 13]. and surrounded by hypoenhancing oedematous
parenchyma [4, 5, 7–10, 13].
Albeit non-validated, an APN severity score
9.1.3 Abscess-forming has been proposed to identify those patients at
Pyelonephritis and Prediction high risk for deterioration and includes clinical
of Severity features such as diabetes, tachycardia, hypoten-
sion, persistent fever and pyuria along with imag-
If undiagnosed, APN may progress to form intra- ing signs including global renal enlargement,
renal abscesses, which appear as peripheral round pelvicalyceal air, infected hydronephrosis,
small- (Figs. 9.10 and 9.11) or moderate-sized effacement of renal sinus and poor contrast excre-
(Fig. 9.12) nonenhancing fluidlike collections tion [17].
a b c
Fig. 9.10 Focal APN with tiny abscess formation at the (arrows), which on delayed excretory phase (arrow in c)
upper third of the right kidney in a 34-year-old immuno- appeared to be surrounded by hypoenhancing oedematous
suppressed male. Nephrographic phase CT (a, b) showed parenchyma
two centimetric nonenhancing fluidlike cortical areas
a b c
Fig. 9.11 Bacterial APN in a 30-year-old female. surrounded by thin rim-like enhancement and by hypoen-
Nephrographic (a) and excretory (b) phase CT acquisi- hancing oedematous parenchyma. Follow-up CT (c) after
tions showed minimally enlarged left kidney with multi- antibiotic therapy showed near-complete normalization of
ple centimetric fluidlike abscess cavities (arrowheads) APN changes
92 A. Vella and M. Tonolini
a b c
Fig. 9.12 Abscess-forming APN in a 30-year-old female intraparenchymal abscesses (arrowheads) of the right kid-
with fever, hypotension, abdominal pain and vaginal dis- ney, measuring up to 3 cm in size, with central fluidlike
charge shortly after removal of intrauterine contraceptive content and irregular peripheral enhancement
device. Nephrographic phase CT (a–c) showed three
a b c
Fig. 9.13 Bilateral long-standing APN in a 70-year-old CT (a–c), both kidneys showed polar regions (arrows)
female with malaise, weakness and weight loss after with poor medullary enhancement and calyceal
improperly treated, recurrent UTIs. At contrast-enhanced deformities
9.1.4 L
ong-Term Sequelae of Acute “scarring” seen as focal or lobar cortical thinning
Pyelonephritis with underlying calyceal distortion from retraction
of papillae (Fig. 9.13). Ultimately long-standing or
In our experience CT represents the most reliable recurrent UTI may cause segmental atrophy of the
modality to perform follow-up of APN (Figs. 9.4, affected kidney or diffuse reduction of renal size
9.7, and 9.11). Unfortunately, despite clinical and and parenchymal thickness [4, 5, 7–10, 13].
laboratory improvement, imaging appearances of
APN may persist for weeks or months during or
after therapy, and CT follow-up may thus prove 9.2 Differential Diagnosis
confusing for the clinician. As discussed in the of Acute Pyelonephritis
Introduction, currently there is convincing evidence
on the potential detrimental effect of APN on renal The main differential diagnosis of focal APN is
function. Anatomically, the long-term anatomic represented by renal infarction (RI), which most
sequelae of APN consist in irreversible parenchy- commonly occurs secondary to atrial fibrillation,
mal destruction. Corresponding CT findings consis- systemic infections such as endocarditis and
tent with chronic pyelonephritis include renal sometimes coagulopathies or antiblastic thera-
9 CT Imaging and Differential Diagnosis of Acute Pyelonephritis 93
a b c
Fig. 9.14 Ventral infarct of the lower third of right kid- arrows) characteristic of renal infarctions. Note adjacent
ney mimicking renal abscess: at CT (a–c) the nonenhanc- region of hypoenhancing ischaemic—oedematous paren-
ing parenchymal region (*) causes minimal bulging of the chyma (+). Consistent clinical history and lack of acute
renal contour without formation of a round-shaped cavity phase reactants confirmed diagnosis over infection
shows preserved capsular “brim” enhancement (thin
pies. Albeit the clinical context is generally dif- (a) Clinical manifestations and laboratory data
ferent, patients may present with similar (b) Associated inflammatory-type perinephric
symptoms and leukocytosis may be present [18]. fat stranding and fascial thickening
At CT imaging, the infarcted renal parenchyma is (c) Poorly defined interface between the affected
differentiated from APN by the presence of the area and surrounding parenchyma
“cortical brim” sign, which is a thin layer of cap- (d) Presence of microabscesses (Fig. 9.16)
sular enhancement representing preserved flow (e) Regression at follow-up imaging [4, 5, 7–
to the capsule through collateral vessels, overly- 10, 13]
ing the nonperfused RI (Fig. 9.14).
A universal and highly specific indicator of Furthermore, diffuse changes which may be
renovascular compromise, the “cortical brim” confused with APN may be observed in the set-
sign may be also observed in renal venous throm- ting of non-infected acute urinary obstruction
bosis along with “striated nephrogram”. (Fig. 9.17), including perinephric fat stranding
Multifocal reversible changes closely resembling and delayed and attenuated nephrogram; how-
RIs (Fig. 9.15) are the hallmark of a characteristic ever in these occurrences, hydronephrosis with a
yet uncommon syndrome, namely, acute renal detectable cause is generally observed.
failure (ARF) with loin pain (LP) and patchy renal Finally bilateral renal changes are commonly
vasoconstriction (PRV) which generally develops observed after chemotherapy, which may corre-
after anaerobic exercise, sometimes with other spond to either acute interstitial nephritis (AIN)
precipitating factors such as heavy alcohol inges- or acute tubular necrosis (ATN): the former
tion, upper respiratory infections and medication mostly occurs after ipilimumab and sorafenib
(analgesics and diuretics) use. Luckily, ARF-LP- treatment and unspecifically appears as oedema-
PRV has a relatively good prognosis since symp- tous renal enlargement; conversely ATN results
toms and renal impairment are transient, and renal from toxic damage to the tubular epithelial cells.
scarring does not occur [19, 20]. In both entities, “streaky” parenchymal hypoat-
Sometimes, unifocal APN may raise concern tenuation zones similar to multifocal APN may
for the presence of a neoplastic lesion: useful be observed; analogously to RI, the preserved
considerations to differentiate APN from tumour “cortical brim” sign may be useful to distinguish
include: ATN from APN [21].
94 A. Vella and M. Tonolini
a b
c d
Fig. 9.15 Characteristic CT appearance of acute renal wedge-shaped nonenhancing parenchymal regions
failure with loin pain and patchy renal vasoconstriction (arrowheads), resulting from temporary vasoconstriction
syndrome in a 58-year-old female: corticomedullary (a, of renal vessels, without function impairment and scarring
b) and corresponding nephrographic (c, d) phase images at follow-up imaging (not shown) (Adapted from Open
showed normal-sized kidneys with scattered infarct-like access ref. no. [19])
9 CT Imaging and Differential Diagnosis of Acute Pyelonephritis 95
a b
c d
Fig. 9.16 Atypical mass-forming APN in a 44-year-old laboratory findings. Bilateral multifocal non-Hodgkin
female with abdominal pain and fever. Combined lymphomatous infiltration in a 35-year-old male present-
nephrographic-excretory CT urography showed moder- ing with testicular mass: CT (c) showed several small-
ately swollen, hypoenhancing ventral aspect at middle sized hypovascular foci in both kidneys and intrahepatic
third of the right kidney (arrowheads) without liquefac- masses (§); the latter appearance is closely similar to a
tion. The wedge-shaped appearance on coronal image (b) unilateral APN (d) which shows enlarged left kidney with
and gallbladder oedema (thick arrow in a) favoured infec- intraparenchymal hypoattenuating bands, plus microab-
tion over tumour, which was confirmed by clinical and scesses (thin arrows)
96 A. Vella and M. Tonolini
a b
c d
Fig. 9.17 Acute urinary obstruction without infection in delayed and attenuated nephrogram (b–d) compared to
a 55-year-old male with tiny stone at the distal right ureter contralateral kidney, mild fluid stranding of ipsilateral
(arrows in a, d). Note upstream hydronephrosis (+), perinephric fat (* in c, d)
9 CT Imaging and Differential Diagnosis of Acute Pyelonephritis 97
Massimo Tonolini
a b c
d e f
g h i
Fig. 10.1 A 63-year-old male admitted to emergency sistent with emphysematous pyelonephritis. MRI follow-
department because of high fever, dysuria and distended up (e–g) better showed parenchymal oedema of the right
tender abdomen was diagnosed with decompensated dia- kidney, intraparenchymal fluid collections (plus in
betes mellitus, severe renal impairment (7.5 mg/dl serum T2-weighted image (f)) and ipsilateral fascial thickening
creatinine), markedly increased C-reactive protein and (thin arrows in (g) with fat saturation); conversely gas was
metabolic acidosis. Initial ultrasound (a) showed enlarge- less perceptible (arrowhead in T1-weighted image (e)).
ment of the right kidney, with parenchymal hyperechoic The patient’s clinical conditions and laboratory changes
bands (arrowheads), posterior acoustic shadowing and slowly improved during conservative treatment including
previously unknown congenital left renal aplasia. After haemodialysis, repeated unenhanced CT studies (h, i)
ureteral stenting (thick arrows), multiplanar unenhanced showed progressive decrease of renal emphysematous
CT images (a–d) confirmed enlarged solitary right kidney changes and the patient ultimately obviated the need for
with strongly hypoattenuating gaseous components, con- nephrectomy (Adapted from Open Access Ref. no [16])
such as bubbly, linear, streaky or crescent- fusely altered with or without focal tissue necro-
shaped. The use of intravenous contrast is sis, fluid-
containing abscesses and delayed
reserved for those patients with preserved renal excretion (Fig. 10.1). Other CT findings include
function. The nephrographic enhancement is dif- variable degrees of parenchymal enlargement
10 Imaging of Extrarenal Spread, Fistulising and Atypical Pyelonephritis 101
and destruction and possible associated condi- rium and thrombocytopenia. However, conserva-
tions such as urolithiasis and obstruction. tive treatment fails in almost one-third of cases.
Compared to CT, MRI (Fig. 10.1) is more sensi- Nephrectomy is not associated with improved
tive for the presence of parenchymal oedema and survival and should be reserved for EPN classes
fluid collections but is limited in the assessment III and IV with adverse prognostic factors or
of gas which has very low signal intensity failed conservative treatment [3–5, 7, 16–19].
[9–16].
In the past, Wan et al. differentiated type-1
EPN characterised by renal necrosis with paren- 10.2 E
xtrarenal Spread of Acute
chymal destruction and gas but no fluid collec- Pyelonephritis
tion, from the less aggressive type-2 EPN lacking
renal or perirenal fluid collections, respectively, As discussed in the previous chapter of this book,
with 69 and 18% mortality rates. Nowadays, acute pyelonephritis (APN) may worsen as tiny
EPN should be more comprehensively staged suppurative foci coalesce leading to the formation
according to classification proposed by Huang of variable-sized round or geographic collections:
and Tseng (Table 10.1). Included in the staging these abscesses are progressively demarcated by a
system as grade I EPN, emphysematous pyelitis more or less thick and irregular inflammatory
corresponds to intraluminal gas in the collecting wall. Albeit sonography may identify abscesses
system only and represents a milder form with as hypo-anechoic cavities without internal colour
better prognosis [9–16]. flow signals, multidetector CT is by far superior
Alternatively, gas may be detected in the uri- in the assessment of APN complications such as
nary tract after surgery, instrumentation or cath- abscesses (Fig. 10.2) [10–12, 20–22].
eterisation, occasionally when fistulisation with When APN is not timely recognized and
the gastrointestinal tract occurs and exceptionally treated, intrarenal abscesses may cross or rupture
from penetrating trauma [13, 14, 16]. through the renal capsule and extend into the
Nowadays, with a timely CT diagnosis, con- perirenal space and sometimes even progress to
servative management of EPN is increasingly involve other retroperitoneal compartments.
feasible and effective, particularly in classes I Perinephric abscesses (PNAs) represent orga-
and II, resulting in decreased mortality, currently nized collections of purulent material which may
below 25%. The aggressive treatment includes either result from a urinary tract infection, from
resuscitation, intravenous fluids and antibiotics, superinfection of a pre-existing haematoma or
glycaemic control, dialysis and drainage of urinoma or form separately from the kidney such
obstruction as needed. The risk factors for unfa- as in haematogenous dissemination. Cross-
vourable outcome include higher CT grade, sectional CT imaging consistently and compre-
shock, emergency haemodialysis, altered senso- hensively depicts PNAs extending from or
abutting the adjacent kidney. The characteristic
imaging appearance includes a central near-water
Table 10.1 Classification of emphysematous pyelone-
hypoattenuation which occasionally contains gas
phritis proposed by Huang and Tseng (Adapted from
Open Access Ref. no [16]) bubbles, corresponding to pus and liquefaction,
surrounded by a peripheral enhancing wall and
Class Description
by regions of decreased parenchymal enhance-
I Emphysematous pyelitis—gas in collecting
system only ment reflecting non-necrotic infected kidney.
II Intraparenchymal gas only (no extrarenal Representing the hallmark of the mature abscess,
involvement) the ‘rim’ enhancement may be more or less (typi-
IIIA Gas extending into the perinephric space cally several millimetres) thick, intense and often
IIIB Extension of gas into the pararenal spaces irregular (Figs. 10.2, 10.3 and 10.4). In the proper
IV Emphysematous pyelonephritis in solitary clinical setting, the CT diagnosis of PNA is rela-
kidney or bilateral involvement tively straightforward and dictates appropriate
102 M. Tonolini
a b c
Fig. 10.2 An 18-year-old female with clinical and labo- peripheral enhancement (arrowheads) consistent with an
ratory signs of acute urinary infection and inconclusive abscess, which measured approximately 4 × 3 cm and pro-
ultrasound findings underwent unenhanced (a) and post- truded ventromedially into the perinephric space.
contrast (b) multidetector CT. The anterior labrum of the Repeated contrast-enhanced CT (c) showed decreased
right kidney showed mixed attenuation enlargement size and purulent content of the abscess after antibiotic
(plus) with nonenhancing centre and thin, irregular therapy
a b c
Fig. 10.3 In a 72-year-old male with history of urolithia- trally the kidney. The very thick, irregular peripheral
sis and recurrent urinary infections, unenhanced (a) and enhancement (arrowheads) and fluidlike content were
post-contrast (b) CT acquisitions showed extensive inho- consistent with an abscess. Despite mild size decrease at
mogeneous abnormality of the posterior aspect of the left follow-up CT (c) after 3 weeks of in-hospital treatment,
kidney (plus) which largely occupied the dorsal perineph- nephrectomy was ultimately performed to relieve the
ric and posterior pararenal spaces, thus displacing ven- infection
treatment with image-guided percutaneous drain- by a variably thick capsule with relatively lower
age plus antibiotics [10–12, 20–22]. signal intensity which enhances strongly after gad-
As discussed in the appropriate chapter of this olinium contrast (Fig. 10.5) [21, 23].
book, although hampered by longer examination The most important differential diagnoses of a
time and need for cooperation, MRI is an increas- PNA include:
ingly attractive option to comprehensively image
renal infections without the use of ionizing radia- (a) Haematomas
tion. At MRI, the mature renal abscess appears as (b) Urinomas (Fig. 10.6)
a fluid collection with fluidlike high T2-weighted (c) Complex cystic masses (Fig. 10.7a–c)
signal and internal restricted diffusion, surrounded (d) Necrotic renal tumours (Fig. 10.7d–f)
10 Imaging of Extrarenal Spread, Fistulising and Atypical Pyelonephritis 103
a b c
d e f
Fig. 10.4 In a 73-year-old diabetic woman hospitalized with perinephric abscess. The abscess was treated by per-
because of malaise and weight loss, unenhanced (a) and cutaneous drainage (thick arrow in (e)) and ultimately
post-contrast (b–d) multidetector CT showed anterior dis- resolved (f). The incidentally detected 3-cm left renal
placement of the right kidney by a 7-cm hypoattenuating mass with strong, early enhancement (arrows) consistent
mass (plus) with nonenhancing fluid content (plus) and with renal cell carcinoma was subsequently treated by
uneven peripheral enhancement (arrowheads), consistent nephrectomy
Apart from the trauma setting, a perinephric collections with enhancing rim and septa from
haematoma may result from ruptured neo- chronic inflammation; the diagnostic hallmark of a
plasms (particularly angiomyolipoma), vascu- urinoma is its opacification on delayed excretory-
lar lesions (such as aneurysms, arteriovenous phase CT acquisition (Fig. 10.6) [28, 29].
malformations or vasculitides), bleeding dia- Finally, rim-enhancing abscess lesions with
thesis or excessive anticoagulation: the diagno- internal inhomogeneity and thick, enhancing
sis is suggested by acute clinical manifestations, septa commonly raise a concern for a cystic or
dropping haematocrit and by the fact that necrotic neoplasm which may suggest the need
thickened perirenal septa and acute haematoma for biopsy or close follow-up (Fig. 10.7). The
have higher unenhanced attenuation than the differential diagnosis of a complex cystic renal
renal parenchyma [24–27]. lesion requires careful assessment of presence
Urinomas may develop after iatrogenic injury and features of calcifications, quantification of
or trauma or result from increased intraluminal internal attenuation and post-contrast enhance-
pressure secondary to acute or chronic obstructive ment, multiloculation, number and thickness
uropathy. The extravasated urine shows near-water of septa, mural thickness, nodularity and
CT attenuation and MRI signal intensity, but enhancement. An infectious process is sug-
chronic urinomas may appear as complex fluid gested by the consistent clinical features and
104 M. Tonolini
a b c
d e f
g h i
Fig. 10.5 A 37-year-old female had persistent fever and perinephric space (c). After percutaneous CT-guided
pain following right-sided lithotripsy and ureteral stenting drainage (thick arrow in (d)) yielded pus, MRI showed
(thick arrows) because of lithiasis and urinary infection. persistence of subcapsular abscess (plus) with inhomoge-
Unenhanced (a) and post-contrast (b, c) multidetector CT neous, non-haemorrhagic content (e–g) and thin periph-
images showed severe compression of right kidney by eral enhancement (h). MRI follow-up showed progressive
hypoattenuating subcapsular collection (plus) with thin decrease (plus in (h) at 8 weeks) and ultimate resolution
peripheral enhancement consistent with abscess, which ((i) after 4 months) of the abscess
extended distally to the lower renal pole into the inferior
a b
c d
Fig. 10.6 A 70-year-old male patient with benign pros- (c) revealed strong hyperattenuation of the perinephric
tatic hyperplasia suffered from acute right flank pain. and pararenal collection (plus) corresponding to extrava-
Performed to investigate suspected ureteral colic, unen- sated urine from forniceal rupture. The urinoma (plus)
hanced CT (a) showed moderate right-sided hydronephro- was clearly depicted by three-dimensional volume render-
sis plus a sizeable fluidlike collection (plus) which ing images (d) in its size and spatial relationship to the
surrounded the renal pelvis and proximal ureter, extend- kidney, pelvis and proximal ureter. Note Foley catheter
ing into the medial perinephric space. The collection (thick arrow in (d)) in the bladder, filled by calculi from
showed thin peripheral enhancement (arrowhead in (b)) chronic urinary retention. The urinoma ultimately
after intravenous contrast which was initially interpreted resolved on conservative treatment. (Adapted with per-
as suggestive of infection. The nephrographic phase and mission from Ref. no. [53])
urinary excretion were normal. Delayed phase acquisition
the medulla and cortex, leading to a progressive encountered in approximately two-thirds of cases.
parenchymal destruction of the kidney which is The poorly understood pathogenesis involves an
characteristically replaced by lipid-laden ‘foamy’ incomplete immune response to a subacute bac-
macrophages (xanthoma cells). Further extension terial infection superimposed on long-standing
of XGPN to the perinephric space is commonly urinary obstruction. Almost invariably unilateral,
106 M. Tonolini
a b c
d e f
Fig. 10.7 A 62-year-old diabetic female with recurrent to investigate suspected renal colic and/or pyelonephritis.
urinary infection was requested CT (a–c) on the basis of The left kidney showed a 7-cm centrally nonenhancing
sonographic suspicion of renal abscess. The large right- mass (plus) with irregular peripheral enhancement (arrow-
sided renal lesion showed water-like attenuation on unen- heads). Despite perinephric fat stranding (asterisk) and
hanced scans (a), peripheral and septal calcifications mild fascial thickening, the presence of ipsilateral renal
(arrowheads) and absent enhancement on both nephro- vein thrombosis (thin arrows) favoured necrotic renal cell
graphic (b) and excretory phases (c), thereby excluding an carcinoma over abscess, as confirmed at surgery and
infectious nature. A 58-year-old female with left-sided pathology
abdominal pain and low-grade fever underwent CT (d–f)
XGPN mostly occurs in middle age, with a pre- ing to dilated calyces and abscesses filled with pus
dilection for perimenopausal women with history and debris (Fig. 10.11a) and amorphous central
of urolithiasis and long-standing urinary infec- hyperechoic structures with acoustic shadowing
tion or obstruction. Compared to EPN, XGPN representing ‘staghorn’ lithiasis; however these
affects diabetic patients in 10% of cases only. complex ultrasound findings invariably require
The clinical manifestations are non-specific, multidetector CT for a correct characterisation,
often insidious compared to the severity of the including intravenous contrast medium unless
imaging abnormalities. Symptoms include low- contraindicated by renal impairment. Cross-
grade fever, flank pain and tenderness, malaise, sectional imaging findings include an enlarged,
weight loss, lethargy, leukocytosis and pyuria. non-functioning kidney with poor and heteroge-
Sometimes a palpable mass is clinically appreci- neous contrast enhancement. The majority (75–
ated. E. coli and P. mirabilis are the commonest 90%) of cases have obstructing pelvis or ureteral
identifiable microorganisms [32, 33]. lithiasis, often in a central ‘staghorn’ configura-
In XGPN, the initial sonographic evaluation tion. The destroyed parenchyma is replaced by
shows extensive replacement of the normal renal multiple rounded hypodense cavities representing
architecture by hypo-anechoic masses correspond- dilated, pus-filled calyces (Fig. 10.8): recognising
10 Imaging of Extrarenal Spread, Fistulising and Atypical Pyelonephritis 107
a b c
d e f
Fig. 10.8 A 48-year-old obese female with history of formed to relieve pyonephrosis (as seen in maximum
left-sided pyelolithotomy 15 years earlier was hospital- intensity projection (MIP) reconstruction). Six weeks
ized with presumptive diagnosis of acute pyelonephritis. later, after stent removal, contrast-enhanced CT (e, f) con-
Ultrasound (a) showed extensive left renal replacement firmed poorly enhancing renal parenchyma and uneven
by large hypo-anechoic regions (plus) with poorly percep- calyceal dilatation; the enlarged left kidney occupied and
tible residual parenchyma. Unenhanced (b, c) CT images compressed the ipsilateral perirenal and pararenal spaces.
confirmed renal parenchymal thinning with sizeable, con- After prolonged antibiotics, laparoscopic nephrectomy
fluent water-attenuation cavities (plus) and ‘staghorn’ cal- was performed. Histopathology diagnosed xanthogranu-
cific lithiasis of the renal pelvis and upper and lower lomatous pyelonephritis. (Adapted from Open Access
calyces. Ureteral stenting (thick arrows in (d)) was per- ref.no [37])
the hydronephrotic pattern of the fluidlike cavities component and iso- to slightly T2 hypointense
is crucial for a correct diagnosis. The highly spe- [10, 11, 21, 32–38].
cific fatty xanthomatous deposits with negative CT The combination of characteristic CT fea-
attenuation are detected in approximately 30% of tures, particularly:
cases. Contrast excretion into urine is rarely seen
at diagnosis. Furthermore, CT readily detects (a) Non-functioning kidney
extrarenal extension of XGPN into the perinephric (b) Central lithiasis
space and other adjacent structures such as the (c) Calyceal dilatation
posterior pararenal space and psoas muscles. (d) Perinephric involvement
Although less used in this setting, MRI may depict
similar changes, with a lower sensitivity for neph- is strongly suggestive of XGPN, a diagnosis
rolithiasis. The pus-filled cavities show fluidlike which is generally confirmed by histopathology
very high T2-weighted signal intensity and vari- on the nephrectomy specimen. The imaging diag-
ably hypointense T1 signal depending on the pro- nosis is challenging in atypical cases, such as in
tein concentration; conversely the solid parts may absence of calculi (10% of cases) and the rare
be T1 isointense or hyperintense from adipose (below 10% of cases) focal XGPN which appears
108 M. Tonolini
as a minimally enhancing renal mass and is com- ment even in acutely ill patients and in non-
monly misinterpreted as bacterial abscess or functioning kidneys and represents a consistent
tumour [10, 11, 21, 32–37]. basis to choose between conservative, percutane-
ous or surgical treatment [41].
Muscular abscesses such as those involving
10.4 Fistulising Renal Infections the psoas present on cross-sectional imaging
with variable enlargement of the muscle belly
Unrecognised acute or chronic pyelonephritis compared to the contralateral one. CT generally
may further breach through the anterior or poste- shows a hypoattenuating, sometimes multilocu-
rior renal fasciae and involve other retroperito- lated, lesion with peripheral ‘rim’ enhancement.
neal compartments, most often the posterior Similarly, at MRI muscle abscesses appear as
pararenal spaces, the iliopsoas and quadratus fluidlike cavities with low T1-weighted, high
lumborum muscles (Fig. 10.9) and occasionally T2 signal intensity and strong ‘rim’ enhance-
to the abdominal wall (Fig. 10.10) giving rise to ment. Additional findings suggesting infection
more or less extensive abscess collections. over haemorrhage or tumour include indistinct
Urinary tract fistulisation represents an abnormal margins, obliteration of the surrounding fat
communication between the renal parenchyma planes and occasionally air-fluid levels; although
(nephro-) or the pelvis (pyelo-) and other struc- uncommon, the presence of gas bubbles is con-
tures: nowadays, the vast majority of urinary fis- sidered specific [41–44].
tulas are iatrogenic in origin, secondary to Nowadays, psoas abscesses are most com-
surgical interventions or percutaneous proce- monly secondary to direct infectious spread from
dures such as nephrostomy, nephrolithotomy or adjacent organs such as the kidneys and urinary
extracorporeal shock wave lithotripsy. Nowadays, tract, the bowel, the lumbar spine or the aorta.
cases of renal fistulas from penetrating trauma, When faced with a retroperitoneal abscess, the
tumours or infections are occasionally encoun- radiologist should suggest the likely cause
tered [39, 40]. between complicated urinary infection, gastroin-
Multidetector CT represents the mainstay testinal lesions, musculoskeletal and exception-
imaging modality to image fistulising complica- ally aortic infections (Table 10.2). Generally
tions, as it promptly provides a comprehensive encountered in association with HIV infection,
diagnosis of retroperitoneal infectious involve- intravenous drug abuse, immunosuppression or
a b c
Fig. 10.9 A 78-year-old female with urinary infection ised by fluidlike content and peripheral ‘rim’ enhance-
and previously unknown multicystic chronic kidney dis- ment consistent with muscle abscess from renal
ease underwent unenhanced (a) and post-contrast (b, c) fistulisation. The patient did well with conservative treat-
multidetector CT. The posterior aspect of the left kidney ment; the abscess was unchanged and anechoic at ultra-
was seen adherent and communicating (arrows) with an sound follow-up (not shown)
enlarged quadratus lumborum muscle (plus), character-
10 Imaging of Extrarenal Spread, Fistulising and Atypical Pyelonephritis 109
a b c
d e f
Fig. 10.10 A 64-year-old female presented to emer- the perinephric, posterior pararenal spaces and abdominal
gency department with low-grade fever and painful ery- wall muscles, to form a large abscess (plus) that displaced
thematous swelling in her right lumbar region, without the superficial fascia. Percutaneous drainage (thick arrow
any previous surgical or interventional procedures. Urgent in (f)) yielded 500 ml of pus from P. mirabilis infection.
unenhanced (a) and post-contrast (b–e) CT images Follow-up unenhanced CT (f) confirmed disappearance of
showed right kidney with reduced, poorly functioning the abscess. Later on, laparoscopic nephroureterectomy
parenchyma, calcific pelvicalyceal stones. A fluid- was performed, and surgical pathology confirmed exten-
containing track with enhancing walls (arrows) consistent sive renal infection breaching through the renal capsule
with spontaneous fistulisation was seen crossing through
Table 10.2 Causes of psoas muscle abscesses DM, the rare primary iliopsoas abscesses origi-
Source Main underlying conditions nate from haematogenous spread and are diag-
Urinary Acute pyelonephritis nosed when no obvious local cause can be
Renal abscess identified [44–46].
Pyonephrosis In current urological practice, spontaneous
Xanthogranulomatous nephrocutaneous fistulas (NCFs) without history
pyelonephritis of surgery or other instrumentation are excep-
Digestive tract Fistulising Crohn’s disease tionally encountered, invariably associated with
Colonic diverticulitis long-standing nephrolithiasis and chronic UTI. A
Complicated acute appendicitis NCF involves the development of an abnormal
Perforated colorectal cancer communication between the kidney and the skin,
Musculoskeletal Pyogenic spondylodiskitis classically crossing through the retroperitoneum
Spinal tuberculosis and abdominal wall structures following the low-
Infectious sacroiliitis est resistance points such as Petit’s triangle and
Vascular Infected aortic aneurysms the Grynfeld quadrilateral. Most reported cases
Prosthetic vascular infection are associated with ‘staghorn’ calculi and poorly
Haematogenous Primary psoas abscess functioning kidneys and attributed to XGPN,
110 M. Tonolini
a b c
Fig. 10.11 Four months after lithotripsy, a 45-year-old and proximal and mid-ureter, a residual stone fragment
female with diabetes, HIV infection and ‘staghorn’ neph- (thin arrow in (b)) and ipsilateral adenopathies (arrow-
rolithiasis experienced a painful lumbar swelling. Careful head in (a)). Furthermore, a thin fluidlike track with
inspection revealed a cutaneous ulcer on her left flank enhancing wall (arrows in (c)) consistent with nephrocu-
draining smelly greenish fluid. Compared to previous taneous fistulisation was recognised, directed postero-
studies (not shown), contrast-enhanced multidetector CT inferiorly through the posterior pararenal space and
(a–c) showed appearance of hydronephrosis with enhanc- abdominal wall to reach the skin orifice (Partially repro-
ing inflammatory urothelial thickening along the pelvis duced from Open Access Ref.no [39])
pyogenic infections such as renal abscesses or (c) A surgical road map for nephrectomy and fis-
pyelocalyceal diverticula, tuberculosis, renal tula debridement
trauma or malignancies. The characteristic clini- (d) Identification of abscesses amenable to
cal manifestation is flank or lumbar tenderness drainage [40, 52]
and swelling with a cutaneous orifice draining
urine or pus [47–52]. Particularly in patients with non-functioning
In the past, most patients were investigated kidneys and complex lithiasis, nephrectomy plus
with fluoroscopic retrograde pyelogram and or fistulectomy is the standard surgical treatment
fistulography: the injected contrast medium which prevents sepsis, that should be planned
directly opacified the abnormal tract and urinary after interventional treatment of pyonephrosis
collecting system, without providing any cross- and abscesses with stenting or percutaneous
sectional information on the involved renal and drainage.
perirenal anatomical structures [40, 47, 51]. Conservative treatment with antibiotics is
Conversely, CT comprehensively and noninva- reserved for debilitated patients [47, 51].
sively depicts the fistulous track even in poorly or
non-functioning kidneys (Fig. 10.11). When con-
trast excretion is preserved, the NCF may be seen
References
opacified on delayed excretory CT acquisitions
obtained 20–120 min after intravenous injection. 1. Kumar S, Ramachandran R, Mete U et al (2014)
In the setting of urinary fistulisation, CT reliably Acute pyelonephritis in diabetes mellitus: single cen-
provides: ter experience. Indian J Nephrol 24:367–371
2. Garg V, Bose A, Jindal J et al (2015) Comparison of
clinical presentation and risk factors in diabetic and
(a) Key information about size, parenchymal non-diabetic females with urinary tract infection
thickness and function of the involved assessed as per the european association of urology
kidney classification. J Clin Diagn Res 9:PC12–PC14
3. Aboumarzouk OM, Hughes O, Narahari K et al
(b) Comprehensive characterisation and extent (2014) Emphysematous pyelonephritis: time for a
assessment of the underlying infectious or management plan with an evidence-based approach.
neoplastic disease Arab J Urol 12:106–115
10 Imaging of Extrarenal Spread, Fistulising and Atypical Pyelonephritis 111
extracorporeal and endourological treatment of uro- 46. Mallick IH, Thoufeeq MH, Rajendran TP (2004)
lithiasis. Insights Imaging 5:677–689 Iliopsoas abscesses. Postgrad Med J 80:459–462
40. Yu NC, Raman SS, Patel M et al (2004) Fistulas of the 47.
Antunes AA, Calado AA, Falcao E (2004)
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24:1331–1352 30:316–318
41. Tonolini M, Campari A, Bianco R (2012) Common 48. Ansari MS, Singh I, Dogra PN (2004) Spontaneous
and unusual diseases involving the iliopsoas muscle nephrocutaneous fistula--2 unusual case reports with
compartment: spectrum of cross-sectional imaging review of literature. Int Urol Nephrol 36:239–243
findings. Abdom Imaging 37:118–139 49. Singer AJ (2002) Spontaneous nephrocutaneous fis-
42. Zissin R, Gayer G, Kots E et al (2001) Iliopsoas tula. Urology 60:1109–1110
abscess: a report of 24 patients diagnosed by 50. Qureshi MA (2007) Spontaneous nephrocutaneous
CT. Abdom Imaging 26:533–539 fistula in tuberculous pyelonephritis. J Coll Physicians
43. Muttarak M, Peh WC (2000) CT of unusual ilio- Surg Pak 17:367–368
psoas compartment lesions. Radiographics 20(Suppl 51. Charles JC (1990) Nephrocutaneous fistula. J Natl
1):S53–S66 Med Assoc 82:589–590
44. Cronin CG, Lohan DG, Meehan CP et al (2008)
52.
Cooper SG, Richman AH, Tager MG (1989)
Anatomy, pathology, imaging and intervention of the Nephrocutaneous fistula diagnosed by computed
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45. van den Berge M, de Marie S, Kuipers T et al (2005) 53. Tonolini M (2011) Spontaneous perinephric urinoma
Psoas abscess: report of a series and review of the lit- complicating obstructive uropathy {Online}. EuroRAD
erature. Neth J Med 63:413–416 URL: http://www.eurorad.org/case.php?id=9710
MRI and DW-MRI of Acute
Pyelonephritis (APN) 11
Andrea Veltri, Agostino De Pascale,
and Dario Gned
plicated APN should be suspected, and a second- coils, and parallel imaging has been helpful in
line imaging test has to be performed as well. increasing the applications of DW sequences. In
Computed tomography (CT) or magnetic resonance particular, the introduction of parallel imaging,
imaging (MRI) examination allows precise defini- such as sensitivity encoding (SENSE), which
tion of the inflammatory areas and evidence of allowed reduction in the echo-train length (TE)
abscesses [1, 14–15]. As patients with noncompli- and the K-space filling time, led to considerably
cated APN are mostly women of childbearing age, less motion artifacts at image acquisition, thus
MR might be chosen as the preferred imaging tech- enabling high-quality DW images of the body to
nique, and CT should be performed only in the case be acquired. Hence, DWI might be useful in dif-
of contraindications or logistical problems (i.e., ferentiating APN, with the advantage of lower
long wait before the availability of an MRI) [16]. costs and execution times than gadolinium-
MRI, using a parallel imaging technique acqui- enhanced MRI (GE-MRI). The following protocol
sition, is able to perform dynamic enhanced stud- is used at our institution.
ies, with diagnostic accuracy comparable to CT
[17]. It does not use ionizing radiation, and it is
equipped with considerable contrast resolution. 11.3 M
RI and DW-MRI Diagnosis
Between sequences performed in a basal setting, of APN
diffusion-weighted magnetic resonance imaging
(DW-MRI) has recently gained particular interest Our study protocol is presented in Table 11.1. As
[18]. It is realizable by analyzing the spin dephas- summarized in Table 11.2, the MRI findings con-
ing and signal loss caused by random motion along sistent with APN include:
magnetic field gradients. The apparent diffusion At basal MRI:
coefficient (ADC), as a quantitative parameter cal-
culated from the DW-MRI acquisition, combines • Changes in renal volume (kidney enlarge-
the effects of capillary perfusion and water diffu- ment, presumably due to edema from active
sion in the intracellular extravascular space. infection) often associated with perinephric
The development of echo-planar imaging inflammatory fluid and stranding of the peri-
(EPI), high-gradient amplitudes, multichannel nephric fat (Fig. 11.1a, b, c)
a b
d
c
Fig. 11.1 (a) Axial SPAIR SENSE show right kidney SPAIR SENSE show thin perirenal effusion. (d) Axial 3D
enlargement due to edema. (b) Axial SPAIR SENSE show FFE T1w Dixon show abnormal cortico medullary inter-
fat stranding around caudal right kidney pole. (c) Axial face consistent in poor/absent delineation of cortical layer
After the administration of contrast medium renal sinus, with the renal parenchyma some-
(GE-MRI), on T1-weighted sequences: times demonstrating a striated appearance.
These abnormalities indicate hypoperfusion
• Reduction of parenchymal contrast enhance- secondary to arteriolar vasoconstriction and
ment in the affected area. Multiple areas can inflammatory response (Fig. 11.3a, b).
readily be affected, and in most cases lesions are • Abscessed areas, as fluid lesions delineated by a
well-defined, wedge-shaped areas with their peripheral halo dilation of the collecting system
bases at the periphery and apexes toward the (mild, moderate, marked) (Fig. 11.3c, d, e, f).
a b
Fig. 11.2 (a) Axial DWI SENSE show wedge shaped corticomedullary focal hyperintensity. (b) ADC map at high b
value show restricted ADC corresponding to DWI SENSE hyperintense lesion
a b c
d e f
Fig. 11.3 (a) Axial 3D FFE T1w enhanced Dixon show TE_100 T2w SENSE and Axial SPAIR T2w show well
reduction of parenchymal contrast enhancement in the defined superior left pole mass with intermediate T2w sig-
affected wedge shaped area. (b) Axial 3D FFE T1w nal and thickened periferal wall, consistent in macroab-
enhanced Dixon show multiple fluid filled lesion in the scess. (e, f) Axial DWI (b800) show marked hyperintensity
affected area consistent with microabscess. (c, d) Coronal of the mass with clear restricted diffusion in ADC map
11 MRI and DW-MRI of Acute Pyelonephritis (APN) 117
11.4 R
ole of MRI and DW-MRI represent restricted diffusion. Dealing with
in the Diagnostic Algorithm functional DW-MRI, in our series the mean
ADC value was 2.38 ± 0.14 × 10−3 mm2 s−1,
APN is a topic that has remained relatively with a range of 1.99–2.76 × 10−3 mm2 s−1. In
neglected in terms of imaging research, and its areas of affected parenchyma, ADC value in
diagnosis is still a challenge. None of the clini- mm2/s was found to be consistently lower
cal signs or laboratory biochemical markers at (mean 1.385; minimum 1.109, maximum 1.717)
presentation allow discrimination between a compared with healthy parenchyma (mean 2.383;
few small lesions and multifocal or abscessed minimum 1.989, maximum 2.763) (Fig. 4).
ones [15]. Thus, imaging techniques are needed Comparing DW-MRI with gadolinium-
to assess the severity of kidney involvement enhanced (GE) MRI for diagnostic accuracy in
and to plan the antibiotic therapy. Diagnostic APN in 163 patients with noncomplicated APN,
imaging plays a role in looking for previous we found DWI-MRI achieving 95.2% sensitivity,
occult structural or functional abnormalities 94.9% specificity, a 96.9% positive predictive
that may require intervention, to assess those value, a 92.3% negative predictive value, and
patients at significant risk of more life-threaten- 94.6% accuracy.
ing complications as in diabetic, elderly, or Several other reports noted the utility of non-
immunosuppressed patients, to balance the enhanced MRI, particularly DWI, in the diagno-
severity of the infection, and to evaluate the sis of APN. Kuniyoshi et al. used non-enhanced
extent of organ damage subsequent to a resolved MRI with DWI to detect foci in children with
acute infection. Second-line imaging tests (CT APN, showing high-intensity lesions as well
or MRI) should be systematically used to define [28]. In another study, 39 children (mean age,
the presence, extent, and type of parenchymal 5.7 years) with suspected APN underwent MRI,
lesions and to reveal complications (such as including DWI and gadolinium-enhanced
abscess or perirenal fluid collections), in order T1-weighted imaging (Gd-T1-WI). The sensitiv-
to tailor interventions to the specific clinical ity and specificity of the DWI were 100% (32/32)
contexts [19, 20]. and 93.5% (43/46), respectively [29].
Our interest in APN originated from the The high diagnostic agreement between
observation of the increasing frequency of this DW-MRI and GE-MRI provided an interesting
disease and from the uncertain indications in starting point for gaining a new perspective on
the literature with regard to the opportunity to the diagnostic management of APN. In fact,
perform DW-MRI [21–25]. DWI provides DW-MRI of the kidney seems to be a feasible,
information about the molecular translational rapid, and reliable method as quantification of
motion of water, which can be affected by dis- ADC values can be useful in diagnosing noncom-
ease. This DW finding is probably secondary to plicated APN. The high diagnostic agreement
compressive alterations due to edematous between GE-MRI and DW-MRI offers new per-
swelling and inflammatory parenchymal dam- spectives in diagnostic management, enabling
age responsible for interstitial space reduction, monitoring of APN in a short time without use of
with a resulting decrease in the diffusivity of ionizing radiation or administration of paramag-
water molecules. The degree of restricted diffu- netic contrast medium. We can assume the use of
sion is affected by various factors, including the DW-MRI, together with the performance of the
type of pathogenic organism, the concentration usual basal sequences T1 and T2, in the acute
of inflammatory cells and bacteria, the degree phase, possibly in the ED, affecting minimally
of viscosity, and the protein level [26–27]. ADC (negligible time is required) the workflow of the
is a measure of the degree of molecular water MRI service, thus allowing a timely therapeutic
motion. Lesions of high signal intensity on approach.
high-b-value images correspond to lesions of Thereafter, in case of hospitalization, an exam
low signal intensity on the ADC map, and they with paramagnetic contrast as first examination
118 A. Veltri et al.
Table 11.3 Diagnostic
algorithm of acute Suspected APN
pyelonephritis
DW-MRI DW-MRI
negative positive
3-week DWI-MRI,
Stop
to assess response to treatment
should be systematically used to better define the jects or slightly sedated claustrophobic ones.
presence, extent, and type of parenchymal Dealing with costs too, DW-MRI is an interesting
lesions and to reveal complications (such as tool for detecting noncomplicated APN, thanks
abscess or perirenal fluid collections), in order to to its inherent cost and its potential impact on the
tailor interventions to the specific clinical con- suitability and timeliness of treatment.
texts [19, 20].
The subsequent checks, performed about
every 3 weeks until complete resolution of the
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grammed with DWI alone (Table 11.3). 1. Craig WD, Brent JW, Travis MD (2008) From the
Additionally, DW-MRI is an alternative to archives of the AFIP, pyelonephritis: radiologic-
dynamic investigation in all cases where there are pathologic review. Radiographics 28:255–276
2. Schappert SM, Rechtsteiner EA (2011) Ambulatory
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5. Georgi A, Reddy YNV, Gautam G (2012) Diagnosis 18. Hagmann P, Jonasson L, Maeder P, Thiran JP, Wedeen
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Cross-Sectional Imaging of Renal
Cyst Infection 12
Massimo Tonolini
Most usually, RCI manifests acutely with or systemic infection. In this setting, enhancement
fever, lumbar pain and flank tenderness and ele- by intravenous contrast medium (CM) is generally
vated serum inflammatory markers such as leuko- warranted unless contraindicated. However, partic-
cytes and C-reactive protein (CRP). Alternatively, ularly in patients with ADPKD and ACKD, the
imaging findings suggestive of RCI may be unex- degree of renal function should be carefully
pectedly encountered in patients with urinary or assessed, and the potential benefits of a comprehen-
unexplained sepsis. In either case, RCI usually sive CM-enhanced CT examination should be
represents a potentially life-threatening situation weighed against the concern for CM-induced neph-
which requires aggressive treatment including rotoxicity. As most European radiologists do, we
percutaneous or surgical drainage to eradicate strongly suggest to follow the indications found in
infection [3–5]. the most recent European Society of Urogenital
The only specific and gold standard criterion Radiology (ESUR) guidelines [3, 4, 9].
for diagnosing RCI is represented by cyst aspira- At CT, infected renal cysts are depicted as
tion yielding bacteria and neutrophils, but is uni- or multilocular hypoattenuating renal col-
commonly not performed unless when percuta- lections with an enhancing peripheral rim of
neous drainage is felt indispensable. Urine and variable thickness (Figs. 12.1 and 12.2).
blood cultures are frequently negative, even in Indeed, RCI are indistinguishable from renal
confirmed cases. In the majority of situations, the abscesses resulting from other mechanisms
diagnosis is challenging and relies on consistent including haematogenous spread, extension
clinical and laboratory features plus imaging from extra-urinary inflammation and ascend-
exclusion of cystic bleeding [3–5]. ing urinary infection. A possible diagnostic
pitfall is represented by misinterpretation of
compressed functioning renal parenchyma as
12.3 Cross-Sectional Imaging an abnormal ‘rim’ enhancement surrounding a
of Renal Cyst Infection fluid collection. Although exceptional, the
presence of gas is highly specific for bacterial
When assessing patients with urosepsis or suspected infection. Furthermore, renal abscesses may
renal infection, radiologists should thoroughly variably extend into the perirenal and some-
search for abnormalities of the characteristic, well- times even pararenal spaces [3, 10–13].
known appearance of uncomplicated RCs. The latter In this setting, the aims of cross-sectional
appear anechoic with posterior through transmission imaging include:
at ultrasound, homogeneous with water-like CT
attenuation and markedly T1-hypointense and (a) To exclude cystic haemorrhage
T2-hyperintense MRI signal intensity. Suspicious (b) To differentiate RCI from parenchymal
features such as mural thickening or irregularities, infection (acute pyelonephritis)
calcifications or peripheral or septal contrast (c) To identify pyocysts within polycystic kidneys
enhancement should be absent [6–8]. (d) To detect hydronephrosis and infected pyo-
The diagnosis of RCI should be suggested when nephrosis, which require emergency urinary
faced with size increase or changed mural or intra- drainage
luminal features of a benign cyst known from previ-
ous imaging or reports. Sonographically, infected However, according to some authors, CT
cysts show highly variable echogenicity, often allows a confident diagnosis of RCI in only a
resulting in complex collections with through trans- minority (less than 20%) of cases, and unremark-
mission, and are thus unreliably differentiated from able findings are observed in approximately one-
haematomas and tumours. In our experience, in half of patients with consistent clinical and
most cases the diagnosis of RCI is made during CT, laboratory features [4].
which represents the mainstay technique to compre- Although its accuracy has not been pre-
hensively investigate patients with suspected renal cisely quantified, MRI probably offers supe-
12 Cross-Sectional Imaging of Renal Cyst Infection 123
a b
c d
Fig. 12.1 Unenhanced (a) and portal-venous phase tures were consistent with a diagnosis of acute pyelone-
contrast-enhanced (b) CT study previously performed for phritis. She had no significant predisposing factors for a
reasons unrelated to the urinary tract in a 39-year-old complicated urinary tract infection. Compared to the pre-
female depicted a 4-cm, predominantly exophytic simple vious study, repeated contrast-enhanced CT (c, d) showed
cyst (*) at the middle third of the right kidney, with char- the known renal cyst with unchanged size and shape, and
acteristic features including round shape, well-demar- with appearance of a thin, enhancing peripheral rim
cated contour, homogeneous fluid attenuation and absence (arrowheads). In absence of CT signs of renal parenchy-
of enhancing walls or septa. More than 2 years later, the mal infection, superinfected cyst from probable ascending
patient suffered from right abdominal and flank pain: in infection was diagnosed and successfully treated with
the emergency department, clinical and laboratory fea- intravenous antibiotics
rior diagnostic capability compared to CT in walls and septa (Fig. 12.3) [3, 10, 11].
the diagnosis of RCI. Renal abscesses are con- Furthermore, the implementation of diffusion-
sistently depicted at MRI as T1-hypointense, weighted imaging (DWI) may improve differ-
heterogeneously T2-hyperintense collections, entiation of infected from uncomplicated cysts
with characteristic thickened and enhancing on the basis of abnormal DWI signal intensity
124 M. Tonolini
a b c
d e f
Fig. 12.2 A 79-year-old male with comorbidities includ- enhanced CT (c–e) showed development of abscess-like
ing ischemic cardiomyopathy and chronic kidney disease collections with enhancing periphery (arrowheads) in the
had a few non-enhancing renal cysts (*), as previously same site of the dominant cysts of each kidney. Follow-up
depicted during aortic CT angiography (an unenhanced CT after intravenous antibiotics (e) showed decreased size
scan, b arterial phase acquisition). Months later, during of the infected cysts (arrows)
hospitalisation for unexplained septic fever, contrast-
and decreased apparent diffusion coefficient haemorrhage or renal colic from coexistent uroli-
(ADC) values: in fact the non-enhancing puru- thiasis. The majority (approximately 80%) of
lent content made up of inflammatory exudate, patients with ADPKD experience acute flank pain
bacteria and necrosis shows marked diffusion at least once during their lifetime. Although its
restriction (Fig. 12.3) [14, 15]. true incidence is unknown, cyst bleeding is more
More recently, as further discussed in the fol- common than RCI and may be further compli-
lowing chapter of this book, (18)-fluorodeoxy- cated by rupture with pericystic and/or retroperi-
glucose positron-emission computed tomography toneal haemorrhage. Spontaneous renal bleeding
(18F-FDG PET/CT) has been increasingly typically presents with acute lumbar or abdominal
reported as the most reliable modality to diag- pain, signs of haemodynamic impairment and
nose RCI [4, 16]. laboratory evidence of blood loss palpable mass
and hypovolemic shock, which warrant immedi-
ate investigation. Alternatively, manifestations
12.4 Differential Diagnosis may be nonspecific with variable degrees of hae-
of Renal Cyst Infection modynamic compromise [3, 17, 18].
To the radiologist’s eye, the hallmark of recent
Clinically, in patients with known cystic renal dis- haemorrhage is represented by the identifica-
orders, particularly if hereditary or extensive, the tion of high-attenuation effusion (in the range
sudden onset of flank pain mostly suggests cystic 40–90 Hounsfield units, HU) blood compared to
12 Cross-Sectional Imaging of Renal Cyst Infection 125
a b c
d e f
g h i
Fig. 12.3 A 47-year-old female with polycystic kidney (ADC, e) indicating restricted diffusion, and thickened
suffered from lumbar pain, pyuria and persistent fever wall (arrowheads) with strong enhancement after gado-
despite empiric antibiotic therapies. Initial MRI (a–f) linium contrast (f). Cyst superinfection was confirmed
showed a 6-cm lower right pole cyst (arrows) with hetero- and treated with percutaneous aspiration. Follow-up MRI
geneously abnormal signal intensity compared to the (g–i) showed decreased size (3 cm) of the infected cyst
other fluid cysts on both T2- (a, b) and precontrast (arrows) with unchanged signal intensity (g) and restricted
T1-weighted (c) acquisitions, marked hyperintensity on diffusion (h), reduced thickness of enhancing wall (arrow-
high b-value (800 s/mm2) diffusion-weighted imaging heads in i).
(DWI, d) and visually low apparent diffusion coefficient
the renal parenchyma on precontrast CT acquisi- ‘debris’ is confusing and does not allow confi-
tion, sometimes with an internal fluid-fluid level. dent differentiation between blood and pus. The
CT has absolute sensitivity for detection of sub- role of ultrasound is limited by the unreliable
capsular and perinephric haematomas. However, differentiation of clotted blood from dense pus
the identification of collections with more or and from solid tissue. Conversely, MRI reliably
less heterogeneous, hyperattenuating internal detects recent blood with high T1 signal inten-
126 M. Tonolini
sity accompanied by variable signal changes on dominant polycystic kidney disease: attributes and
limitations of the current modalities. Nephrol Dial
T2-weighted sequences corresponding to hae-
Transplant 27:3746–3751
moglobin degradation products [3, 17–19]. 5. Migali G, Annet L, Lonneux M et al (2008) Renal
Infectious inflammatory masses with or without cyst infection in autosomal dominant polycystic kid-
perirenal extension often appear as complex inde- ney disease. Nephrol Dial Transplant 23:404–405
6. Israel GM, Bosniak MA (2004) MR imaging of cys-
terminate (Bosniak category III) cystic lesions.
tic renal masses. Magn Reson Imaging Clin N Am
Furthermore, misinterpretation of abscesses ad 12:403–412
necrotic or cystic tumours is not uncommon, par- 7. Israel GM, Bosniak MA (2008) Pitfalls in renal mass
ticularly because of the concern for increased inci- evaluation and how to avoid them. Radiographics
28:1325–1338
dence of renal cell carcinoma (RCC) in patients
8. Hindman N (2016) Cystic renal masses. Abdom
with ADPKD and ACKD. When confronted with a Radiol 41:1020–1034
heterogeneously enhancing lesion, helpful clinical 9. European Society of Urogenital Radiology (2016)
discriminating features include: ESUR guidelines on contrast media 9.0. Available at:
“www.esur.org/guidelines”
10. Craig WD, Wagner BJ, Travis MD (2008) Pyelonephritis:
(a) The acute clinical context radiologic-pathologic review. Radiographics 28:255–
(b) Laboratory changes consistent with infection 277. quiz 327-258
(c) History of benign cyst in the same location 11. Demertzis J, Menias CO (2007) State of the art: imag-
ing of renal infections. Emerg Radiol 14:13–22
(d) Coexistent imaging signs of acute infectious
12. Stunell H, Buckley O, Feeney J et al (2007) Imaging
pyelitis or pyelonephritis of acute pyelonephritis in the adult. Eur Radiol
17:1820–1828
At CT or MRI imaging, abscess is favoured 13. Erkoc R, Sayarlioglu H, Ceylan K et al (2006) Gas-
forming infection in a renal cyst of a patient with auto-
over tumour by the identification of perirenal fat
somal dominant polycystic kidney disease. Nephrol
inflammatory stranding and thickened Gerota’s Dial Transplant 21:555–556
fascia and by markedly restricted diffusion (simi- 14. Kita Y, Soda T, Terai A (2009) Diagnosis and local-
lar to brain abscesses) compared to areas of cys- ization of infected renal cyst by diffusion-weighted
magnetic resonance imaging in polycystic kidney dis-
tic degeneration within RCC [2, 3, 7, 8].
ease. Int J Urol 16:918–919
15. Goyal A, Sharma R, Bhalla AS et al (2013) Diffusion-
weighted MRI in inflammatory renal lesions: all that
References glitters is not RCC! Eur Radiol 23:272–279
16. Lantinga MA, Drenth JP, Gevers TJ (2015) Diagnostic
criteria in renal and hepatic cyst infection. Nephrol
1. Thomsen HS, Levine E, Meilstrup JW et al (1997)
Dial Transplant 30:744–751
Renal cystic diseases. Eur Radiol 7:1267–1275
17. Diaz JR, Agriantonis DJ, Aguila J et al (2011)
2. Degrassi F, Quaia E, Martingano P et al (2015)
Spontaneous perirenal hemorrhage: what radiologists
Imaging of haemodialysis: renal and extrarenal find-
need to know. Emerg Radiol 18:329–334
ings. Insights Imaging 6(3):309–321
18. Tonolini M, Ierardi AM, Carrafiello G (2015) Letter
3. Tonolini M, Rigiroli F, Villa F et al (2014)
to the editor: spontaneous renal haemorrhage in end-
Complications of sporadic, hereditary, and acquired
stage renal disease. Insights Imaging 6:693–695
renal cysts: cross-sectional imaging findings. Curr
19. Chicoskie C, Chaoui A, Kuligowska E et al (2001) MRI
Probl Diagn Radiol 43:80–90
isolation of infected renal cyst in autosomal dominant
4. Jouret F, Lhommel R, Devuyst O et al (2012)
polycystic kidney disease. Clin Imaging 25:114–117
Diagnosis of cyst infection in patients with autosomal
Nuclear Medicine
in the Management of Patient 13
with Kidneys Intracystic Infection
Daniele Penna, Vincenzo Militano,
Vincenzo Arena, Angelina Cistaro,
and Ettore Pelosi
Table 13.1 Inflammation tracer carateristics Scintigraphic assessment, however, lacks ana-
Ideal characteristics of an infection-imaging tomical landmarks, rendering the topographic
radiopharmaceutical localization of sites of abnormal tracer uptake
– High sensitivity and specificity difficult. In this clinical setting, the precise local-
– Differentiates infection and inflammation ization achieved with SPECT/CT in a single
– Differentiates acute and chronic infection imaging step and with greater diagnostic accu-
– Rapid clearance from circulation/background racy may provide a tool for guiding invasive tis-
– No significant normal uptake in liver, spleen, sue sampling procedures and further treatment
intestine, bone, bone marrow, kidneys, and muscle
planning.
– Easy to prepare, low cost, and easily available
A study aimed at investigating the potential
– No toxicity and free of immune reaction
advantage of 111In-labeled WBC-SPECT/CT
compared with SPECT alone evaluated 14
13.1.2.1 67Ga-Citrate patients with various sites of suspected infection.
67
Ga-citrate (Ga) has been used for imaging infec- The authors concluded that SPECT/CT improved
tion for almost four decades, since its discovery in the accuracy of anatomic localization of foci of
the early 1970s [3]. Ga was used for the investiga- abnormal WBC uptake and led to modification in
tion of fever of unknown origin, acute or chronic clinical management [5].
osteomyelitis, and the diagnosis of infections in
immunocompromised patients. Although Ga scin- 13.1.2.3 Labeled Antigranulocyte
tigraphy shows high sensitivity in detection of both Antibodies
acute and chronic infections, it has several draw- The preparation of radiolabeled leukocytes is
backs that limit its clinical application. Its specific- laborious, requires specialized staff and dedi-
ity is relatively low because of early physiologic cated expensive equipment, and can be hazardous
excretion through the urinary system and delayed because of blood-product handling.
excretion through the bowel and because of the nor- The advantages of radioimmunoscintigraphy
mal biodistribution to the liver. Ga is a bone-seeking over techniques involving labeled autologous leu-
tracer, accumulating in areas of bone remodeling. It kocytes for imaging infection have to do mainly
is also a tumor-seeking agent, accumulating in such with the simplicity of its use due to the fact that
tumors as lymphoma or hepatoma. Physiological there is no need for blood-product handling.
hepatic, bowel, and renal uptake can either mimic or Indications for labeled antigranulocyte antibody
mask foci of infection localized inside or in the scintigraphy include the suspicion of osteomy-
vicinity of these organs. Optimal Ga imaging may elitis, fever of unknown origin, abdominal infec-
therefore require delayed imaging of up to a few tions, and vascular graft infections [6–8].
days after injection, a disadvantage when diagnos- Correlation of results from this scintigraphic
ing acute infectious processes that may require technique to anatomical imaging modalities is
rapid therapeutic interventions [3, 4]. considered mandatory for accurate diagnosis.
False-positive studies may be the result of
13.1.2.2 Radiolabeled Leukocytes increased vascular permeability. Increased uptake
Labeled WBC imaging using either 99mTc or of labeled antibodies has been observed in peri-
111In has been shown to perform excellently in vascular hematomas and contusions, especially
detecting acute and chronic infections. This test in the delayed phase images obtained 24 h after
has become the nuclear medicine modality of injection. With the additional anatomical infor-
choice in a variety of clinical settings when the mation it provides, SPECT/CT can be of value in
suspicion of an infectious process exists. Clinical excluding or confirming the presence of a hema-
indications for labeled leukocytes scintigraphy toma as the cause of abnormal tracer uptake.
include osteomyelitis, especially in cases where Similar to the performance capabilities of other
infected joint prosthesis or posttraumatic osteo- nuclear medicine procedures, the precise local-
myelitis is suspected. ization of the infected site may be difficult on
130 D. Penna et al.
scintigraphy alone. A study investigating the localization in infection is that cells involved in
value of SPECT/CT in chronic osteomyelitis infection and inflammation, especially neutro-
assessed 27 patients with 29 sites of suspected phils and the monocyte/macrophage, are able to
bone infection and compared planar and SPECT/ express high levels of glucose transporters, espe-
CT imaging after injection of 99mTc-labeled cially GLUT1. The common indications of FDG-
antigranulocyte antibodies [9]. SPECT/CT was PET/CT in infection and inflammation included
able to correctly localize all positive foci detected the following in descending order of accuracy:
on planar and SPECT images. SPECT/CT also sarcoidosis, osteomyelitis, spondylodiscitis,
allowed the differential diagnosis of soft tissue fever of unknown origin, vasculitis, diabetic foot,
infection, septic arthritis, and osteomyelitis. prosthesis (especially hip), and vascular grafts.
Furthermore, following the diagnosis of bone Also it is used for assessing the extent of fungal
involvement, hybrid imaging was also able to dif- infection and evaluation of therapy in infectious
ferentiate between cortical, corticomedullar, and or inflammatory diseases [11].
subperiosteal foci of disease involvement. The
authors concluded that combined SPECT/CT Mechanism of uptake of SPECT and PET
imaging improves the accuracy of radioimmu- SPECT and PET tracer Mechanism of uptake
noscintigraphy for diagnosis of soft tissue infec- 67Ga-citrate and Transferrin and lactoferrin
tion and osteomyelitis [9]. 99mTc-HMPAO receptor binding
migration of leukocytes
99mTc-HMPAO-WBC Migration of leukocytes
13.1.2.4 FDG
111In-oxine-WBC Cellular migration of
Fluorodeoxyglucose (FDG) is currently mainly
leukocytes
used in oncology, neurology, and cardiology and LeukoScan (Tc-anti- Increased vascular
in the study of infectious and inflammatory NCA-90 FAB permeability and binding
disease. antigranulocyte and migration of
FDG has been approved by US Food and Drug antibody) antibody-labeled
granulocytes
Administration (FDA) and European Medicines
18F-FDG Glucose uptake by
Agency (EMEA) and authorized as a diagnostic activated inflammatory
radiopharmaceutical in the diagnosis of infec- cells
tion. Fluorine-18 (18F) is a cyclotron-produced
radioisotope with a half-life of 109.7 min that
undergoes positron decay. [18F]FDG is an
analogue of glucose, whereby the 2-carbon
13.2 Diagnosis of Cyst Infection
hydroxyl group of glucose is substituted with a
fluorine atom (Fig. 13.1). Cyst infection is a diagnostic challenge in patients
Like glucose, [18F]FDG is taken up by cells with autosomal dominant polycystic kidney dis-
via the glucose transporter (GLUT1) and phos- ease (ADPKD) because of the lack of specific
phorylated by hexokinase II (HKII) to form [18F] manifestations and limitations of conventional
FDG-6-PO4; however, unlike glucose, further imaging procedures [12]. ADPKD represents the
metabolism is prevented due to the absence of the most common inherited kidney disease [13]. It is
required 2-carbon hydroxyl, and hence [18F]FDG characterized by the development of fluid-filled
remains trapped within the cell (Fig. 13.2). [18F] cysts in kidney and liver parenchyma, derived
FDG-6-PO4 accumulates in cells over time, lead- from various renal tubular segments and biliary
ing to signal amplification and making this imag- ducts. Cyst growth causes organ enlargement
ing agent a suitable indicator of hexokinase II leading to abdominal and/or loin discomfort.
activity as well as a cell’s need for glucose [10]. Liver cysts are not associated with hepatic dys-
FDG rapidly accumulates at the sites of infec- function, whereas kidney cysts cause end-stage
tion and inflammation with high target-to- renal disease (ESRD) in more than 70% of
background ratio. The mechanism of FDG ADPKD patients. Also, cysts carry significant
13 Nuclear Medicine in the Management of Patient with Kidneys Intracystic Infection 131
Fig. 13.2 18F-FDG
metabolism
GLUT 1
P
P
P
P
HKII
P Glycolysis
P
18F]FDG
[ [18F]FDG-6-PO4
tissue infection on the basis of the high metabolic PET/CT n ormalization. The clinical relevance of
activity and increased uptake of the radiolabeled persistent altered PET/CT images to treated infec-
glucose analogue, 18FDG, by inflammatory cells tious diseases remains unclear. The literature in
[22]. Importantly, 18FDG is not nephro- or hepa- oncology supports that the follow-up by 18FDG-
totoxic and has been successfully used in patients PET/CT of therapeutic responses to chemo- or
with renal function ranging from mildly reduced radiotherapy varies from 3 to 12 weeks depending
GFR to ESRD [14, 23]. First, 18FDG-PET alone upon the type of cancer and the administered ther-
proved helpful in identifying or excluding renal apy. However, the pathophysiology of infection is
and hepatic cyst infection in case reports and two intrinsically different from neoplasia, and cyst
retrospective series [14, 20, 24]. To further infection is associated with the additional chal-
improve the localization of infectious sites, PET lenge of antibiotic diffusion into a chronically
was combined with CT to integrate metabolic damaged organ and a cystic cavity. Consequently,
data from PET with anatomical information from 18FDG-PET/CT probably represents an optimal
CT [22]. In our series, 18FDG-PET/CT yielded tool for the detection and localization of pyocysts
positive results in 87% of cyst infection cases in ADPKD patients, but its role in the follow-up
[17]. PET/CT was considered as positive for cyst after antibiotic therapy remains uncertain. PET/
infection when the uptake of 18FDG was focally CT in ADPKD patients with suspected cyst infec-
increased around at least one cyst in comparison tion offers the additional advantage of entirely
with the physiological accumulation in the paren- scanning the abdominal cavity, thereby occasion-
chyma and was located at distance from the pelvi- ally identifying non-cystic inflammatory disor-
calyceal excretion. PET/CT yielded two ders and adjusting the therapy. PET/CT results
false-negative results in a diabetic RTR during the significantly changed the management of 26% of
immediate posttransplantation period and in a cases [17]. Moreover, PET/CT confirmed two
62-year-old nondiabetic woman with stage IV kidney cyst infections, although both patients did
CKD. By contrast, three liver pyocysts could be not meet all four of the standardized criteria [19].
percutaneously drained only after localization by The advantages of 18FDG-PET/CT are rapid
PET/CT. The median delay between the onset of imaging, minimal labor intensity, high target-to-
symptoms and PET/CT imaging was 9 days, and background ratio, high interobserver agreement,
the mean maximal standardized uptake value and a simultaneous coregistration with low-dose
(SUVmax) reached 5.1 ± 1.7 g/mL. The measure- CT without administration of contrast medium
ment of SUVmax allows standardized quantifica- [23]. Limitations of PET/CT include its cost,
tion of the inflammatory process in addition to the restricted availability, and relative inability to reli-
visual evaluation [23]. Repeated measurements of ably distinguish infectious from noninfectious
SUVmax may help follow up the inflammatory pro- inflammation or malignancy. The differentiation
cess over time. Piccoli et al. [18] reported on the of 18FDG accumulation in residual functional
clinical management of ten patients with sus- renal parenchyma from that in inflammatory cells
pected cystic infection, which was tailored upon lining pyocysts remains debatable. The distinc-
18FDG-PET/CT results. PET/CT identified five tion between cyst infection and pyelonephritis
kidney and one liver cyst infections. The mean may not be easy. The PET/CT pattern of pyelone-
SUVmax reached 8.4 ± 5.4 g/mL on initial PET/CT phritis usually includes a diffuse 18FDG uptake
images. The follow-up of four patients included a in an edematous cortex and locoregional hyper-
comparative PET/CT performed 3–6 weeks later, metabolic adenopathies, which contrasts with the
which showed a visual reduction of pathological focally increased uptake of 18FDG lining the
18FDG uptake but no significant change of pyocyst. Besides infectious processes, 18FDG
SUVmax. Three patients underwent a third PET/ uptake can be increased in other conditions, such
CT 7–9 weeks after the initial imaging, which dis- as cancer. The actual risk of malignancy in
closed no residual 18FDG uptake. Of note, the ADPKD patients does not seem to be increased
normalization of serum CRP levels preceded [25]. Liver cystadenocarcinoma is very uncom-
13 Nuclear Medicine in the Management of Patient with Kidneys Intracystic Infection 133
mon, and most kidney tumors show low-grade During the follow-up a second CT scan
malignancy leading to low 18FDG uptake. showed the persistence of the right renal cysts
However, “false-positive” rate of 18FDG- PET/ although dimensionally significantly reduced
CT in cyst infection diagnosis remains to be pro- compared to the previous control. In the absence
spectively investigated. Finally, PET/CT has not of a definitive imaging judgment of complete
been evaluated in intracystic bleeding, the main response, a third PET scan was performed. PET
differential diagnosis of cyst infection in ADPKD showed the complete disappearance of the
patients. Accumulation of 18FDG has been abnormal uptake of the radiopharmaceutical at
reported in the setting of extrarenal hematoma the walls of the kidney cysts, still present from a
[26]. In conclusion the 18FDG-PET is a very morphological point of view (Fig. 13.5).
useful method for increasing the accuracy of the In this clinical case, the PET examination,
diagnosis of the infected cyst with a sensitivity of together with clinical parameters, seems to have
77%, a specificity of 100%, and a negative predic- helped, both in the correct diagnosis and in
tive value of 77% [27]. response assessment to the treatment.
13.2.3.2 Case 2
13.2.3 Cases Presentation A 55-year-old patient with hepatorenal polycys-
tic disease went to the hospital for pain in the left
13.2.3.1 Case 1 lumbar region associated with fever. Biochemical
An 81-year-old woman, suffering from poly- examinations showed a high CRP value
cystic hepatorenal disease, was hospitalized (188.3 mg/L), and a possible left renal cyst with
for onset of fever of unknown origin. Following hemorrhagic aspects was detected by contrast-
investigations, because of the suspect of left enhanced CT in the suspect of an active inflam-
acute multifocal pyelonephritis, the patient matory process in this site; the patient was
was treated with ceftriaxone and amikacin. The subjected to antibiotic therapy with amoxicillin.
abdominal CT examination showed the pres- One month later the symptoms disappeared
ence of a renal cyst with diameter of almost completely, and the PCR values were sig-
80 × 90 mm and characterized by homoge- nificantly reduced although not yet in standard
neous fluid content and slightly and uniformly levels, while a second CT scan showed no more
thickened walls in the absence of nodular signs of active left kidney inflammation. In con-
lesions. Then therapy was later stopped due to sideration of the difficult judgment of treatment
the persistence of symptoms and high levels of response, the patient was sent to our clinic for a
inflammatory markers. The patient was thus PET/CT examination. The examination showed
treated with ertapenem getting better results an abnormal uptake of radiotracer at the lower
but not a complete response. She was therefore portion of the known left renal cyst, with a
aimed at our center to perform an 18F-FDG- SUVmax 2.9 (Fig. 13.6).
PET/CT scan. This functional examination In the following months, the patient under-
showed the presence of an abnormal FDG went further antibiotic therapy and was moni-
uptake at the level of the left kidney cyst walls tored with multiple diagnostic tests. It was
(Fig. 13.3). interesting to note that PET scan was the only
The pathological presence of radiotracer at imaging examination able to identify the persis-
this level, indicative of an active inflammatory tent focus of the disease. This finding was fur-
process, suggested the continuation of antibiotic ther reduced by size and fixation in the
treatments. After 37 days a second PET scan subsequent PET control, showing a SUVmax of
showed a good response to the treatment docu- 2.4 (Fig. 13.7).
mented by a significant reduction in the extent A further reduction in this finding was found
and intensity of the abnormal uptake of radio- in the third PET examination, showing a SUVmax
tracer (Fig. 13.4). of 2.0 (Fig. 13.8).
134 D. Penna et al.
Fig. 13.3 PET/CT scan (CT, PET, Fusion, Transaxial and MIP images): diffuse abnormal uptake of 18F-FDG at the
walls of a large kidney cyst indicative of a high presence of inflammatory active cells at this level
One last PET scan was performed when the 13.3 Future Development
patient showed total normalization of inflamma-
tory indices and a complete resolution of the In addition to glucose metabolism, a variety of
symptoms. This last examination showed the targets for inflammation imaging are being dis-
complete disappearance of the radiotracer uptake covered and utilized, some of which are consid-
(Fig. 13.9). ered superior to FDG for imaging inflammation.
In this clinical case, PET has proven to be a We summarize the potential inflammation imag-
good diagnostic tool in evaluating minimal ing targets and corresponding PET tracers and
persistence of inflammatory disease. PET scan, the applications of PET in major inflammatory
used during the treatment, has helped clini- disease.
cians decide on the type and duration of 18F-FDG-PET imaging of inflammation
therapy. tends to give false-positive results, especially in
13 Nuclear Medicine in the Management of Patient with Kidneys Intracystic Infection 135
Fig. 13.4 PET/CT scan (CT, PET, Fusion, Transaxial and MIP images): significant reduction of the abnormal uptake
of radiotracer at the renal cyst wall, indicative of good response to antibiotic treatment
patients with cancer. Moreover, the high tracer oped for PET imaging of inflammation, target-
accumulation in the heart and brain makes it ing different biomarkers from macrophages to
difficult to detect inflammatory foci near those angiogenesis.
organs or tissues. Consequently, new imaging A small survey of the new tracer potentially
tracers and targets for more specific inflamma- available in the next future.
tion detection and therapy evaluation are under
intensive investigation. PET imaging with these
new tracers greatly improved our understanding 13.3.1 Translocator Protein (TSPO)
of the mechanism of inflammation and increased
the diagnostic specificity and accuracy of Formerly known as peripheral benzodiazepine
inflammatory foci. As summarized in Fig. 13.10, receptor (PBR), TSPO is ubiquitously
various radiopharmaceuticals have been devel- expressed in peripheral tissues but is only min-
136 D. Penna et al.
Fig. 13.5 PET/CT scan (CT, PET, Fusion, Transaxial and MIP images): complete disappearance of the abnormal
radiotracer uptake at the renal cyst level, after further antibiotic treatment
Fig. 13.6 PET/CT scan (CT and PET Transaxial images): focal abnormal uptake of 18F-FDG at the level of the lower
portion of a left kidney cyst, due to the presence of active inflammatory cells
13 Nuclear Medicine in the Management of Patient with Kidneys Intracystic Infection 137
Fig. 13.7 PET/CT scan (CT and PET Transaxial images): reduction of the abnormal uptake of radiotracer at the left
kidney cyst after antibiotic treatment
Fig. 13.8 PET/CT scan (CT and PET Transaxial images): further reduction of radiotracer uptake during antibiotic
therapy
imally expressed in the healthy human brain. 13.3.2 Type 2 Cannabinoid Receptor
Previous studies found high TSPO expression (CB2R)
in macrophages, neutrophils, lymphocytes
[28–30], activated microglia, and astrocytes There are at least two subtypes of CBRs in the
[31–35]. PET imaging using TSPO as an endocannabinoid system. The first in vivo PET of
inflammation biomarker has also been reported brain CB2R was performed in 2010 by Horti and
for atherosclerosis detection with promising his group [40]. Promising results on CB2R tar-
results [31, 32, 36, 37]. TSPO PET has also geted PET imaging warrant further applications
been used to image inflamed lung and liver dis- in a wide range of neuroinflammatory diseases
eases [30, 38, 39]. and evaluation of the therapeutic value of novel
138 D. Penna et al.
Fig. 13.9 PET/CT scan (CT and PET Transaxial images): total disappearance of the 18F-FDG cystic uptake, indicative
of complete metabolic response to the treatment
CB2R-related drugs. However, the exact role of otal role in cancer, cardiac/cerebral ischemia,
CB2R in CNS still remains to be fully elucidated, Alzheimer’s/Parkinson’s disease, and response to
and more in vivo studies using relevant disease inflammatory stimuli, especially neuroinflamma-
models should be conducted to get a better tion [43, 44]. Celecoxib is broadly used as a
understanding. selective COX-2 inhibitor to treat inflammatory
diseases. Imaging tracers have also been devel-
oped using celecoxib and some other COX inhib-
13.3.3 Formyl Peptide Receptor (FPR) itors by radiolabeling them with either 18F or
11C. They have been used to image neuroinflam-
FPR is a type of G-protein-coupled receptor mations [45], tumors, or experimental skin
expressed on neutrophils, responsible for the leuko- inflammation [46, 47]. However, most of the
cyte migration cascade in the inflammation process. tracers showed unsatisfactory ex vivo or in vivo
PET using cFLFLFK-PEG-64Cu as FPR-specific properties due to either nonspecific bindings or
ligand could visualize inflammatory foci within the low sensitivity in inflammatory foci or both.
lung in an animal model of lung inflammation
induced by Klebsiella pneumoniae [41].
13.3.5 Interleukin-2 (IL-2)
mune diseases [49], celiac disease [50], and vul- some group used a PET tracer 64Cu-DOTA-
nerable atherosclerotic plaques [51] via SPECT etanercept, to image acute inflammatory process
imaging. However, routine application of this induced by 12-O-tetradecanoylphorbol-13-acetate
technique was limited because the labeling pro- (tetradecanoylphorbol acetate, TPA) [56].
cedures are complex and the spatial resolution of So far, many inflammation-related biomarkers
SPECT is not high enough. Recently, have been identified and investigated as imaging or
Gialleonardo et al. reported the labeling of IL-2 therapy targets, including inflammatory cell metabo-
with N-succinimidyl 4-18F-fluorobenzoate (18F- lism, membrane markers, cytokines, and vascular
SFB) for the synthesis of 18F-FB-IL-2 to detect changes during inflammation. After intensive pre-
activated T lymphocytes in inflammation [52]. clinical studies, some of these targets have been
tested in humans. However, very few of them are
considered to be inflammation specific. With better
13.3.6 Tumor Necrosis Factor-α understanding of the inflammatory reaction in each
(TNF-α) disease type, more sensitive and specific biomarkers
will be identified, and potential new imaging probes
TNF-α is a cytokine that can contribute to cell may be developed to target these biomarkers.
apoptosis and organ dysfunction [53]. Many stud- Moreover, multiplexed imaging with tracers target-
ies show that TNF-α is important in acute immune ing different biomarkers and multimodal imaging by
response to infection, injury, autoimmune, and incorporating PET with other imaging modalities
chronic inflammatory disorders such as rheuma- will also contribute to improved visualization and
toid arthritis [54] and psoriasis [55]. Previously, quantification of the inflammatory diseases.
140 D. Penna et al.
mation with [18F]FEDAC, a radioligand for translo- 45. de Vries EFJ, Doorduin J, Dierckx RA, van Waarde
cator protein (18 kDa). PLoS One 7(9):e4506 A (2008) Evaluation of [11C]rofecoxib as PET tracer
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Part III
Imaging of Lower Urinary and Male Genital
Tract Infections
Ultrasound of Lower Urinary Tract
Infections 14
Emilio Quaia, Antonio G. Gennari,
and Maria A. Cova
frequent in women over their 50s. Reinfection of the colon or bladder [3, 4]. The most prevalent
does not require a specific urologic evaluation pathogen isolated in urine culture of EC patients is
and is managed conservatively with the same E. coli (58% of cases); anyhow various other bacte-
therapy as acute cystitis. Symptoms and bacteria rial and fungal organisms proved to be related with
are the same as the ones detailed for acute blad- EC such as K. pneumoniae, Pseudomonas aerugi-
der infection. nosa, P. mirabilis, Candida albicans and many
CC is a clinical diagnosis, and management is more [3, 4]. Several theories have been postulated
not dependent on imaging, particularly in spo- to explain gas formation. In one the combination of
radic cases. However in cases of several repeated high tissue glucose level, gas-forming pathogens
episodes, imaging helps in defining the underly- and poor tissue vascularisation is all related to
ing cause of symptoms, such as tumours, bladder emphysematous infection. The high-glucose tissue
outlet obstruction and bladder calculi. Typical concentration allows bacteria to produce carbon
findings are non-specific and shared with several dioxide through natural fermentation process [3].
other forms of cystitis. Plain film allows imaging In another, used to explain EC in non-diabetic
bladder calculi. At US evaluation are a focal or patients, albumin is the substrate for gas produc-
diffuse mucosal thickening, irregularities and tion. An impaired host response to pathogens, due
mucosal ulceration of varying intensity. In patients to vascular compromise and impaired catabolism
with a mass protruding in the bladder lumen, in the tissue, is another theory proposed [3]. When
attached to the mucosal surface, it is important to left untreated, mortality rate is as high as 7%.
modify patient decubitus and use colour Doppler Diagnosis relies on radiographic procedures
evaluation to correctly differentiate thrombus rather than in clinical ones. If EC is suspected, a
from bladder cancer. A thrombus generated by a simple plain radiography of the abdomen should
small ulceration modifies its position, contrary to be ordered [4]. Typical findings are a curvilinear
tumour that does not. Contrast-enhanced ultra- radiolucency outlining the bladder wall with or
sound (CEUS) may better demonstrate the without luminal gas associated. US of the bladder
absence of internal contrast typical of thrombus. may reveal an abnormal ticked bladder wall with
dirty shadowing associated. However US find-
ings are not specific for EC.
14.1.2 Emphysematous Cystitis
affect only parts of it or one side more than tion is not a frequent finding and is seen only
another [5]. Moreover submucosa and muscle after healing allowing an easy differential diag-
layer involvement and fibrosis determine a reduc- nosis with schistosomiasis [7].
tion in bladder capacity due to contraction of the
bladder [6]. The ‘bladder neck obstruction’ is a
condition related to eggs entering the muscle cre- 14.2 Prostate
ating a sort of hyperplasia that later evolves in
fibrosis [5]. This condition is typically described Acute prostatitis is a severe, potentially life-
in Egypt [5]. At IVU the formation of submuco- threatening systemic infection [2]. Clinical mani-
sal oedema and pseudotubercles determines hazi- festations are simple and include fever and
ness of the bladder outline with a nodular bladder perineal pain or tenderness, symptoms of lower
wall thickening. Chronic bladder wall irritation UTI such as urgency, frequency or nocturia and,
determines also urothelium penetration and pro- occasionally, obstructive uropathy. It is encoun-
liferation in the lamina propria, creating buds tered in both young sexually active men and in
(von Brunn nests) [5]. These buds evolve into older ones with predisposing risk factors such as
cystic deposits. The latter stage is the formation bladder voiding outlet obstruction usually due to
of cystitis cystica, or cystitis glandularis, when benign prostatic hyperplasia (BPH). Moreover the
intestinal columnar mucin-secreting glands (gob- rate of progression to chronic prostatitis is approx-
let cells) are present [5]. imately 5%. Several theories proved to define the
exact aetiology; however, intraprostatic urinary
reflux is the most widely accepted. The infection
14.1.4 Tuberculosis is generated by infected urine reflux into the ejac-
ulatory and prostatic ducts. Since ducts draining
The pathogenesis, symptoms and pathologic mod- the peripheral zone are positioned more horizon-
ification related with tuberculosis have been eluci- tally than others, most infections occur in the
dated in the previous chapter. Since the peripheral zone. However acute prostatitis may be
genitourinary tract is frequently involved and also related with sexual intercourse, instrumenta-
tuberculosis of the bladder is present in 10–45.6% tion and prolonged catheterisation. Acute bacte-
of patients with urogenital tuberculosis, this pos- rial prostatitis is usually generated by a single
sibility must be kept in mind. In fact, tuberculosis pathogen that in the majority of cases is E. coli,
bacilli reach the urinary bladder from the infected but P. mirabilis, Klebsiella species, Enterobacter
kidney through the ureters. Granulomatous lesion species, P. aeruginosa and Serratia species may
produces tumour-like mass or ulcer. The extensive also produce prostatitis. Symptoms may vary and
fibrosis produced by chronic infection determines depend on the severity of the case but usually
a shrunken, small, urinary bladder (thimble blad- include fever, chills, pelvic pain, dysuria, haema-
der) (see Fig. 3 in Chap. 17). That is why recurrent turia, urinary frequency, a painful ejaculation,
UTI associated with pus, in absence of positive haematospermia and pain localised at genitals,
urine culture for usual pathogens, should always testicles or rectum. An uncommon but threatening
raise the suspicion of urinary tract tuberculosis. complication of acute prostatitis is prostatic
Multiple irregular mucosal masses may be abscess. It usually occurs in immunocompro-
seen at US determined by coalescing tubercles mised or diabetic patients or in ones with pro-
with ulceration and oedema, diffuse wall thicken- longed indwelling urethral catheters.
ing and trabeculation [7]. IVU demonstrates an Imaging techniques are not mandatory to diag-
irregular bladder mucosa, with associated ure- nose acute prostatitis; however transrectal US
teral strictures. The vesicoureteric junction ori- (TRUS) shows an enlarged prostate gland with
fice could be thickened and obstructed, resulting homogeneous hypoechoic parenchyma due to
in vesicoureteric reflux [7]. A contracted, thick- oedema. Colour Doppler and power Doppler US
walled bladder is detected in chronic stages when demonstrate a diffuse increased blood signal [8].
there is bladder fibrosis. Bladder wall calcifica- TRUS may be helpful in the evaluation of compli-
148 E. Quaia et al.
cation of acute prostatitis such as prostatic abscess. usually non-specific. Anyhow, the reproductive
It manifests as a defined round hypoechoic or health is strictly related to a correct diagnosis.
anechoic mass with increased flow signal around it Abscess formation is related to low drug concen-
at colour Doppler evaluation enlargement [8]. tration within the seminal vesicles (SV) due to
Moreover TRUS may guide abscess drainage. low vascularity and is more frequent in patients
undergoing instrumentation or surgery or in dia-
betic patients [10]. Moreover it is often paired
14.2.1 Chronic Prostatitis with a prostatic abscess. In endemic areas, tuber-
culosis and schistosomiasis should be considered
Chronic bacterial prostatitis is quite common and as possible aetiologies.
may manifest as recurring UTI that lasts for at Typical imaging findings of vesiculitis on US
least 3 months. It will affect about two men in ten include diffuse wall thickening [10]. Cystic dila-
at some point during their life; however it is more tion of the seminal vesicles is frequent in acute
common in men between the ages of 30 and 50 but and subacute phase and may be seen at US.
may affect men of any age. Chronic prostatitis is In the initial phase, seminal vesicles are enlarged
sustained by the same bacterial strains isolated in with destruction of convolutions and hypoechoic
acute bacterial prostatitis [2] and is not a sexually areas on US (see Fig. 14.14 of Chap. 14) [11].
transmitted infection. Bacteria eradication is very Abscess formation follows with caseation, cavi-
difficult and challenging due to limited diffusion tation (Fig. 14.1) and fibrosis and may eventually
of antibiotic agents into the gland or to the pres- result in a calcified mass [11].
ence of colonised prostate stones [2]. Moreover In endemic areas of schistosomiasis, postmor-
migration of pathogens persisting in the prostate, tem studies have demonstrated parasite eggs in
in the bladder and in the urethra may determine the SV of approximately 58% of the male cadav-
recurrent cystitis. Symptoms are similar to the ers [11]. Seminal vesiculitis is due to Schistosoma
ones of acute bacterial prostatitis, but they wax eggs deposited into the wall of the SV and may
and wane and usually are less severe compared to lead to SV dilatation and wall calcifications, best
that of acute bacterial prostatitis. The most fre- seen on CT or US [11].
quent symptom is a persistent discomfort or pain
in the pelvic region, mainly at the base of the penis
and around the anus. 14.4 Scrotal Infections
At TRUS the main features of chronic prosta-
titis are the presence of prostatic calcifications Scrotum is a complex anatomical male reproduc-
and calculi. Prostatic calcifications are easily tive structure composed of a dual chamber sac
encountered in older men and are not a specific each of which could be divided into an inner por-
finding of chronic prostatitis; contrary, prostate tion composed by the testis, epididymis and duc-
calculi are more frequent in patients with tus deferens and an outer portion, the scrotal
chronic prostatitis than in general population wall. Both the inner and the outer portion may be
and could be easily identified with TRUS but infected by pathogens. Even though clinical
could be detected also on plain film [9]. examination may guide the diagnosis, symptoms
Moreover an increased colour Doppler blood are shared with other pathological entities such
flow was defined as a marker to identify chronic as testicular torsion that represents a urological
prostatitis [9]. emergency.
a b
Fig. 14.1 In a 50-year-old HIV-positive male with hae- right seminal vesicle, which appeared as hypoechoic,
mospermia, longitudinal (a, b) and transverse (c) transrec- poorly vascularised (colour Doppler image in b) enlarge-
tal ultrasound images showed chronic infection of the ment containing an anechoic liquefied focus (calipers)
UTI is not so frequent in males, epididymitis ally active men. The most frequent pathogens
results from retrograde bacteria seed and infection encountered are Chlamydia trachomatis that
of the epididymis via the urethra through the uri- accounts for two-thirds of acute cases, Neisseria
nary and reproductive system. Epididymis is gonorrhoeae and E. coli. The latter one, which
directly connected with the prostate and SV represents enteric flora, is commonly encountered
through the ductus deferens, so it is the first site of in older patients and homosexuals. Tuberculosis
infection. Bacteria could spread further reaching and brucellosis infection are encountered in immu-
testis and generating an EO. Isolated orchitis is nosuppressed patients. Schistosomiasis may gen-
less frequent and usually related with mumps erate EO, in tropical countries. Clinically patient
virus. Bloodstream route of infection is unusual. presents with pain, tenderness and swelling of a
Acute epididymitis and EO are more common in single scrotum and its content. The most important
young and middle-aged (35–50 years old), sexu- differential diagnosis that has to be made is with
150 E. Quaia et al.
testicular torsion that represents a urologic emer- visualised as cystic lesions with internal septa-
gency. The clinical hallmark of testicular torsion is tions and loculations. Scrotal skin thickening, an
a higher position of the testis within the scrotal enlarged epididymis characterised by increased
sac, contrary to EO testicle will hang low in the echogenicity and calcifications, on the other
scrotum. Moreover in EO the cremasteric reflex is hand, are findings that indicate chronic epididy-
present, and Prehn’s sign (the relief of scrotal pain mitis [14]. Furthermore US may be used to cor-
during elevation of the testicle) may aid in the dif- rectly differentiate EO from testicular torsion and
ferential diagnosis, although non-specific. diagnose EO complications such as abscess for-
Complications of epididymitis and EO include mation and testicular ischaemia. In high-grade
abscesses, testicular ischaemia and pyocele forma- testicular torsion, the testis is completely avascu-
tion. Testicular ischaemia is generated by the lar, and a twisting of the spermatic cord may be
obstruction of venous outflow, related to the tes- depicted. Contrary to low-degree testicular tor-
ticular enlargement and engorgement, and pro- sion, in which intratesticular arteries demonstrate
duces impairment of the arterial blood supply. high-resistance flow signal at spectral analysis
Testicular ischaemia may evolve in segmental or [12]. Abscesses present as hypo- or anechoic
global testicular infarction [12]. In chronic epi- areas of fluid collection, with irregular borders
didymitis, a disease that lasts for over 3 months, with hypoechoic edges [13]. Sometimes intra-
patients have had symptoms for over 5 years. abscess gas is visualised as focal hyperechoic
Palpation may reveal an indurated epididymis with spot with posterior shadowing. At colour Doppler
or without irregular shape. The differential diag- evaluation, the inner part of abscesses is not vas-
nosis includes causes of chronic scrotal pain such cularised; contrary, the outer part demonstrates
as testicular cancer and varicocele. perilesional hyperaemia [13]. An enlarged testis
US is definitely the imaging modality of with reduced vascularisation compared to the
choice in the evaluation of the acute scrotum. An contralateral one is the hallmark for testicular
entirely or partially enlarged hypoechoic or ischaemia [13]. Moreover spectral analysis dem-
hyperechoic (thought to be related to haemor- onstrates increased resistive index compared to
rhage) epididymis is a frequent finding [13, 14]. normal. CEUS is useful in the evaluation of tis-
Diffuse or focal epididymis and testicular sue vascularity, so it helps in differentiating
enlargement associated with a focal or a global necrotic from viable, hypoperfused testis [12].
uneven echotexture are findings suggesting con- Moreover CEUS allows to follow up patients and
current epididymitis or orchitis [13–15]. These monitor the restoration of parenchymal vascular-
areas are usually hypoechoic compared to the isation during therapy or progression to global
adjacent normal parenchyma. At colour Doppler infarction. Anyhow an enlarged, irregularly
evaluation, EO and epididymitis demonstrate hypoechoic testis is not specific for orchitis. In
hyperaemia and hypervascularisation of the fact lymphoma, which represents the most fre-
involved areas. It is well established that colour quent testicular malignancy in middle-aged
Doppler demonstrates a high sensitivity in detect- patients, may present with similar features.
ing scrotal inflammation (see Figs. 4, 5 and 6 of Lymphoma has an infiltrative growth pattern, so
Chap. 15) [13, 14]. In acute epididymitis, the at US evaluation, it may present as single or mul-
spectral analysis of arterial flow demonstrates a tiple areas of reduced echogenicity or as a diffuse
reduced resistive index (below 0.7) compared to enlarged hypoechoic testis without loss of testicu-
normal ones. Also the spectral analysis of testicu- lar shape [12]. Moreover vascularity may be
lar arterial flow is usually lower (below 0.5). A increased, and testicular vascular anatomy is nor-
thickening of scrotal tunica and the presence of mal. Those cases are challenging, and accurate
hydrocele, an anechoic fluid collection that sur- evaluation of patient symptoms and laboratory
rounds the anterolateral aspects of the testis [13], and clinical examination is mandatory. MR is use-
are frequent associated findings. Pyocele may be ful in complicated or inadequately treated patients
present in more serious cases. At US it can be and in ones with unusual US appearance.
14 Ultrasound of Lower Urinary Tract Infections 151
a b
c d
Fig. 14.2 In a 60-year-old male with diabetes, recurrent ultimately corresponded to clinically unsuspected
urinary tract infections and left-sided scrotal swelling, Fournier’s gangrene as better demonstrated by CT (c)
ultrasound (a, b) showed marked oedematous thickening detection of intrascrotal gas. In a different male patient,
of the superficial tissues (*), without hydrocele and signs ultrasound (d) depicted an elongated, hypo-anechoic
of acute orchitis (testis is indicated by calipers), which abscess (between calipers) of the scrotal wall
nonneoplastic bladder masses: radiologic- pathologic 13. Pavlica P, Barozzi L (2001) Imaging of the acute scro-
correlation. Radiographics 1595(4):2006 tum. Eur Radiol 11(2):220–228
8. Seung-Hyup K, Min-Hoan M, Byung-Kwan P (2002) 14. Gottlieb RH, Oka M (2003) Sonography of the scro-
Clinical applications of transrectal ultrasound in tum. Radiology i(1):18–36
the prostate and seminal tract. J Med Ultrasound 15. Schull A, Monzani Q, Bour L, Barry-Delongchamps
10(4):181–190 N, Beuvon F, Legmann P et al (2012) Imaging in
9. Wee A, Shoskes DA (2008) Ultrasound findings in lower urinary tract infections. Diagn Interv Imaging
patients with chronic prostatitis/chronic pelvic pain 93(6):500–508
syndrome. Curr Prostate Rep 6:182–184 16. Kim DJ, Kendall JL (2013) Fournier’s Gangrene and
10. Kim B, Kawashima A, Ryu J-A, Takahashi N, Hartman its characteristic ultrasound findings. J Emerg Med
RP, King BF (2009) Imaging of the seminal vesicle 44(1):1–3
and vas deferens. Radiographics 29(4):1105–1121 17. Levenson RB, Singh AK, Novelline RA (2008)
11. Reddy MN, Verma S (2014) Lesions of the seminal Fournier gangrene: role of imaging. Radiographics
vesicles and their MRI characteristics. J Clin Imaging 28:519–528
Sci 4(4):61 18. Feldman MK (2009) US Artifacts 1. Radiographics
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Derchi LE (2016) Pitfalls in imaging for acute scrotal
pathology. Semin Roentgenol 51(1):60–69
Cross-Sectional Imaging of Urinary
Bladder, Prostate and Seminal 15
Vesicle Infections
Massimo Tonolini
As discussed in the previous chapter of this book, infections in the majority of situations [6]. Compared
ultrasound with colour Doppler represents the to ultrasound, CT consistently detects:
mainstay first-line technique to investigate the
lower urogenital tract, particularly in patients (a) Inflammatory changes in the perivisceral fat
with acute conditions involving the urinary blad- (b) Abnormal gaseous, fluid, abscessual or
der, prostate, penis and scrotum [1–3]. haemorrhagic collections
However, during the last decade, the dramatic (c) Calcific lithiasis in the kidneys and along the
technical advances in multidetector computed urinary tract
tomography (CT) and magnetic resonance imag- (d) Implanted medical devices
ing (MRI) have increasingly provided a compre- (e) More or less subtle thickening and abnormal
hensive multiplanar assessment of genitourinary contrast enhancement of the pyeloureteral
structures and disorders with high spatial and con- and bladder wall
trast resolution. This chapter reviews the CT and (f) Renal and excretory functional information
MRI techniques and imaging appearances of uri- from contrast enhancement [3–5, 7]
nary tract infections (UTIs) affecting the urinary
bladder, prostate and seminal vesicles, with an As discussed in the appropriate chapter of this
emphasis on their differential diagnosis [3–5]. book, in patients with urosepsis or sepsis from
unknown source, CT offers a proven benefit in
detecting the infectious focus and the possible
15.1 CT Technique underlying structural abnormalities of the urinary
and Indications in the Lower tract. The main indications for obtaining CT
Urogenital Tract include:
Indwelling (Foley-type or suprapubic) cathe- otherwise exclude urinary bladder leaks (such
ters should be closed before CT, in order to as those resulting from surgery, obstetric inju-
achieve adequate urinary bladder distension ries or instrumentation) and fistulas. At our
which allows assessing the true mural thickness. Department of Radiology, CT-cystography is
However, this is usually difficult to obtain, since performed, after preliminary bladder emptying,
most patients with chronic lower urinary tract using slow retrograde administration by gravity
dysfunction poorly tolerate bladder filling [4]. of CM diluted 1:10 in saline through the Foley
In our experience, the CT protocol should catheter, until the patient complains of intoler-
include a preliminary unenhanced acquisition, able bladder distension, flow stops or at least
which is generally withheld in young patients 300 mL is injected. Then, volumetric CT of the
to limit the erogated radiation dose and when pelvis is acquired with an adequately distended,
urolithiasis has been ruled out on clinical or uniformly opacified urinary bladder and visu-
imaging grounds. Enhancement by intravenous alised along multiple planes at CT angiogra-
iodinated contrast medium (CM) is warranted, phy window settings (width 600–900 HU, level
unless contraindicated by history of allergy or 150–300 HU) and optionally with additional
impaired renal function. Particularly in septic or maximum intensity projection (MIP) or volume
dehydrated patients with limited urine output, rendering techniques [15–17].
according to the European Society of Urogenital
Radiology (ESUR) guidelines, special care in
ensuring adequate hydration before and after 15.2 MRI Role and Technique
CT is recommended, both to improve urinary
tract opacification and prevent CM nephrotoxic- Up to a few years ago, the use of MRI to inves-
ity [10, 11]. tigate acute abdominal conditions was largely
In the setting of suspected or confirmed UTI, a limited by scanner time availability, lengthy
single breath-hold nephrographic CT acquisition examination, and need for patient cooperation:
is acquired using a 75–85 s delay, which should since then, state-of-the-art scanners have now
encompass the abdomen, pelvis and perineum. significantly decreased most of these limitations.
An optional excretory phase acquired 5–20 min Compared to CT, MRI provides multiplanar
after CM injection visualises the opacified uri- visualisation of the pelvic, genital and perineal
nary collecting systems, ureter and bladder. structures with superior contrast resolution and
Strategies for dose reduction such as automated thus allows better tissue characterisation: for
tube current modulation or, if available, iterative instance, fat-suppressed T2-weighted sequences
reconstruction from raw CT data are recom- easily show detected oedematous changes with-
mended. Modern double- or triple-bolus CT- out the use of intravenous contrast. However,
urography protocols are appealing to radiologists MRI is insensitive for calcifications and gas.
since they provide a comprehensive corticome- Albeit increasingly appealing to avoid irradia-
dullary, nephrographic and excretory imaging tion of the reproductive organs, MRI may still
with reduced effective radiation dose in a single be contraindicated by claustrophobia, early
volumetric acquisition; however CT-urography pregnancy, metallic foreign body in vital sites,
may be misleading in the investigation of sus- cardiac pacemaker or other non-MRI compatible
pected UTI since densely opacified urine in the implanted devices [18–20].
collecting systems, ureters and bladder easily In our experience, MRI is increasingly estab-
masks the subtle urothelial enhancement which is lished as a problem-solving modality to investi-
one of the key signs of active infection [12–14]. gate disorders of the urinary bladder, prostate and
To elucidate the lower urogenital anatomy, seminal vesicles after inconclusive sonographic
multidetector CT studies tailored to the urinary and CT findings or as a first-line examination
tract are routinely visualised along axial, coronal in younger patients. On current high-magnetic
and sagittal planes [4]. field strength MRI scanners, pelvic studies are
In selected patients, performing multidetec- routinely acquired using phased-array coils. The
tor CT-cystography is beneficial to visualise or patient is positioned supine on the scanner table;
15 Cross-Sectional Imaging of Urinary Bladder, Prostate and Seminal Vesicle Infections 157
in males a folded towel is positioned between fluid may provide a panoramic view of the entire
the legs to elevate the scrotum, with the penis urinary collecting systems without the use of
secured at the midline hypogastrium. Most MRI intravenous contrast. Albeit contraindicated in
acquisition protocols heavily rely on multiplanar patients with severely decreased renal function
high-resolution T2-weighted sequences, centred (glomerular filtration rate below 30 mL/min),
in the region of interest, with spectral fat sup- the injection of gadolinium-based CM provides
pression or short-tau inversion recovery (STIR) a comprehensive examination including informa-
in at least one plane to detect parenchymal or tion on enhancement, generally with acquisition
perivisceral oedematous changes (Fig. 15.1). of three-dimensional fat-suppressed gradient-
Optional MR urography sequences using heav- echo T1-weighted sequences such as THRIVE,
ily T2-weighted sequences sensitive to static LAVA or VIBE (Fig. 15.1): however, in our expe-
a b
c d
Fig. 15.1 Usual MR appearance of senile urinary bladder thickening and minimal uniform irregularities along the
with detrusor hypertrophy, in a patient without ongoing mucosal surface. The fat-saturated STIR image (c) and
infectious or neoplastic processes. Sagittal (a) and axial post-gadolinium T1-weighted (d) images exclude oede-
(b) T2-weighted images show moderately distensible matous changes and abnormal contrast enhancement in
bladder filled with urine, with mild circumferential mural the bladder wall and perivesical fat planes (+)
158 M. Tonolini
rience unenhanced MRI is frequently sufficient Concerning the first feature, a circumferen-
to provide the key information on the lower uro- tial wall thickening is commonly encountered
genital structures [3, 4]. on CT studies performed for investigation of
suspected UTI or sepsis, since most patients
experiencing complicated UTIs have a poorly
15.3 Cross-Sectional Imaging distensible, thickened urinary bladder from
of Urinary Bladder Infections underlying chronic conditions such as detrusor
hypertrophy and recurrent infections (Fig. 15.1).
15.3.1 Infectious Cystitis However, in our experience a diffuse wall thick-
ening may correspond to acute UTI, particularly
The cross-sectional imaging diagnosis of acute when:
infectious cystitis (AIC) is suggested by a combi-
nation of three features: (a) Marked (over 1 cm)
(b) Increased compared to previous studies
(a) Oedematous mural bladder thickening
(c) With hypoenhancing dominant muscular
(b) Inflammation of the surrounding fat planes layer corresponding to intramural oedema
(c) Urothelial hyperenhancement (Figs. 15.2 and 15.3)
a b c
d e f
Fig. 15.2 Active infectious cystitis in a 52-year-old dia- polymicrobial infection including Staphylococcus aureus
betic female with dehydration, pelvic and flank pain, and multiresistant extended-spectrum beta-lactamase
pyuria and elevated C-reactive protein (CRP). Unenhanced (ESBL)-positive Escherichia coli (Reproduced from
(a) and contrast-enhanced (b–d) multidetector CT images Open Access Ref.no. [4]). Similarly, in a different male
showed contracted urinary bladder with Foley catheter patient, post-contrast CT (e, f) showed contracted bladder
(thick arrows), marked circumferential mural thickening with marked diffuse bladder wall thickening (*) and uro-
(*) with hypoenhancing oedematous wall and urothelial thelial hyperenhancement (thin arrows) which extended
hyperenhancement (thin arrows). Urine cultures revealed along the suprapubic catheter (thick arrows) track
15 Cross-Sectional Imaging of Urinary Bladder, Prostate and Seminal Vesicle Infections 159
a b
c d
Fig. 15.3 Polymicrobial urinary tract infection (UTI) urosepsis showed increased mural thickening of the uri-
complicated by mural bladder abscess in a 67-year-old nary bladder (*), appearance of inflammatory stranding
male with benign prostatic hyperplasia and indwelling of the perivesical fat planes (+) and development of a
catheter (thick arrows). Four months earlier, contrast- sizeable (over 6 cm) collection attached to the bladder
enhanced CT (a, b) revealed contracted urinary bladder dome (arrowheads) with nonenhancing hypoattenuating
with calcific lithiasis, circumferential mural thickening (10–15 Hounsfield units, HU) content and enhancing
(*) from detrusor hypertrophy and urothelial hyperen- peripheral rim, consistent with abscess which required
hancement (thin arrow in b) consistent with active surgical drainage (Partially reproduced from Open
UTI. Currently, urgent CT (c, d) requested to investigate Access Ref. no. [4])
160 M. Tonolini
should not be overlooked albeit rather subtle, may Compared to CT, MRI provides a superior
be confirmed by performing slab MIP reconstruc- assessment of the urinary bladder wall even with-
tions (Fig. 15.3b) and should be reported as con- out intravenous gadolinium CM. In patients with
sistent with AIC [3, 4, 21]. AIC, MRI shows:
Emphysematous cystitis (EC) is a rare pecu-
liar form of complicated UTI, most usually
(a) Focal or diffuse intramural oedematous
occurring in diabetics, in which gas-forming regions with increased T2-weighted signal
micro-organisms cause the formation of charac- (Fig. 15.5) compared to the usual, uniformly
teristic air-attenuation linear changes within the low signal intensity corresponding to the
bladder wall (Fig. 15.4). The key differential detrusor muscle
diagnosis of EC is intraluminal air from catheter- (b) Inflammatory-type T2 hypersignal of the
isation or urologic instrumentation, alternatively perivesical fat (Fig. 15.6), which is best
from enterovesical fistulisation [4, 7]. appreciable with fat-suppression techniques
a b c
Fig. 15.4 Emphysematous cystitis in a 69-year-old male walls, with associated inflammatory stranding (+) of the
with diabetes, congestive heart failure and chronic perivesical fat planes. Additionally a small-sized fluidlike
obstructive lung disease, suffering from urinary frequency intraprostatic abscess collection (arrowhead in c) was
and pain. Multidetector CT-urography (a–c) revealed dis- noted. Emphysematous cystitis resolved after prolonged
tended urinary bladder with linear gas attenuation changes antibiotic therapy (Partially reproduced from Open Access
(thin arrows) along the right lateral and upper posterior Ref. no. [4])
a b c
Fig. 15.5 Acute infectious cystitis in a 66-year-old bed- contracted bladder with Foley catheter (thick arrows) and
ridden male with urosepsis. After inconclusive abdomino- diffused mural thickening with multifocal high-signal
pelvic CT (not shown), unenhanced MRI including oedematous regions best appreciated with fat saturation
sagittal (a), axial (b, c) T2-weighted sequences showed (c) (Reproduced from Open Access Ref.no. [4])
15 Cross-Sectional Imaging of Urinary Bladder, Prostate and Seminal Vesicle Infections 161
a b c
Fig. 15.6 Acute infectious cystitis with mural bladder the surrounding extraperitoneal fat planes. Additionally,
abscess in an 89-year-old male with acute urinary retention, sagittal T2-weighted image (c) showed a focal thickening
fever, leucocytosis and impaired renal function. Unenhanced (arrows) at the bladder dome with intramural fluid collec-
MRI including MR-pyelographic (a) and axial fat-sup- tion (arrowhead). Repeated CT (not shown) after medical
pressed (b) images revealed bilateral hydronephrosis, con- treatment revealed disappearance of abnormal mural
tracted bladder and prominent inflammatory changes (+) of changes (Reproduced from Open Access Ref.no. [4])
a b c
Fig. 15.7 A 73-year-old male with previous radical pros- the asymmetric mural thickening (*) showed diffuse
tatectomy plus adjuvant radiotherapy for prostate cancer T2-hypointense signal (b) consistent with fibrosis and
and dorsolumbar spine metastases. Contrast-enhanced CT homogeneously enhancing after intravenous gadolinium
(a) showed contracted bladder with asymmetric mural contrast (c). Cystoscopy and biopsies excluded neoplastic
thickening, more pronounced and enhancing (*) on the changes, thus confirming the diagnosis of radiation
right side. MRI confirmed moderately distended bladder; cystitis
hyperaemia, ulcerations, haemorrhage and necro- (bilharziasis) from S. haematobium worms’ infec-
sis. At MRI, the diffuse or focal bladder wall tion is still highly prevalent in sub-Saharan Africa
thickening may show high T2 signal intensity and is acquired through human contact with con-
consistent with inflammation, but abnormal con- taminated water in rural areas. Frequently asymp-
trast uptake is usually not apparent [25]. tomatic, schistosomiasis mostly affects the urinary
Albeit rare compared to the past decade, radia- bladder and distal ureters (60–70%), followed by
tion cystitis may occur following external, intersti- male (prostate, seminal vesicles, testicles and epi-
tial or intracavitary irradiation of pelvic neoplasms didymis) and female (vulva) genital organs. The
[28]. The acute form manifests from 4–6 weeks up schistosoma eggs incite a chronic granulomatous
to 4 months after therapy, involves mucosal ulcer- intramural inflammation, which ultimately leads to
ation and mixed acute and chronic inflammatory a contracted, thick-walled bladder with more or
cell infiltrate in the submucosa, but is usually self- less nodular appearance and frequent mural calcifi-
limiting and conservatively treated. Conversely, cations (Fig. 15.8a, b) [31, 32]. Furthermore, bil-
chronic radiation cystitis usually manifests harziasis has a well-established association with
1–4 years (occasionally even later) after radiation squamous cell bladder carcinoma, which occurs in
and is generally seen at imaging as a contracted younger (mean age 40–49 years) patients with a
bladder with circumferential t hickening. MRI may striking (5–6:1) male predominance. Therefore, in
support this diagnosis by showing T2-hypointense patients from endemic countries, an enhancing
mural signal corresponding to the predominant mural mass should raise suspicion of cancer
interstitial fibrosis; mural enhancement may be (Fig. 15.8c, d) [33–36].
persistently observed even years after treatment At CT, transitional cell carcinoma of the uri-
(Fig. 15.7) [26, 27, 29, 30]. nary bladder appears as uni- or multifocal, gener-
Infections such as genitourinary tuberculosis ally asymmetric wall thickening which enhances
and schistosomiasis should be suspected in patients most prominently at a 60-s delay (Fig. 15.9).
from endemic countries. As discussed in the appro- Tumour is suggested over infection when a soft-
priate chapter of this book, tuberculous cystitis tissue density irregularity is detected at the inter-
develops at a later stage after renal involvement, face between mural thickening and perivesical
and the diagnosis is suggested by clinical history fat. Perivesical invasion is obvious when the neo-
and supported by a characteristic constellation of plasia shows overt growth beyond the outer blad-
imaging findings. Albeit declining, schistosomiasis der wall contour [37, 38].
15 Cross-Sectional Imaging of Urinary Bladder, Prostate and Seminal Vesicle Infections 163
a b
c d
Fig. 15.8 Uncomplicated schistosomiasis in a 46-year- with heterogeneous enhancement along the anterior, right
old male from Egypt, being hospitalised for unrelated rea- lateral and superior bladder aspects, plus thin calcifica-
sons. Contrast-enhanced CT (a, b) showed mild, uniform tions (thin arrows) along the left posterolateral bladder
thickening of the entire bladder wall, without macroscopic wall, and intraluminal stones (arrowhead). Final diagnosis
calcifications and intraluminal vegetations. In a 48-year- was extensive squamous carcinoma superimposed on
old Gambian male with pelvic pain and tenderness, dys- schistosomiasis (Partially reproduced from Open Access
uria and difficult urination, post-contrast (c, d) CT images Ref.no. [4])
showed marked, asymmetric solid mural thickening (*)
Finally, nephrogenic adenoma and malaco- injury or previous surgery causing urothelial
plakia of the urinary bladder mostly occur in metaplasia. Both entities cannot be reliably
diabetics or immunocompromised individual differentiated from chronic UTI or bladder car-
such as those with long-standing HIV infec- cinoma on the basis their unspecific cross-sec-
tion. Whereas the latter is a rare chronic granu- tional imaging features and therefore generally
lomatous condition, the former results from represent incidental diagnoses on endoscopic
long-term irritation from calculi, infection, biopsies [4, 26].
164 M. Tonolini
a b
c d
Fig. 15.9 Muscle-invasive bladder carcinoma in a bladder wall, with an irregular configuration and positive
54-year-old male with urolithiasis (arrows) and long-term contrast enhancement (thin arrows). Radical cystectomy
bladder catheterisation (thick arrows). Unenhanced (a), with orthotopic neobladder reconstruction was performed
portal (b, c) and excretory (d) phase CT images showed (Partially reproduced from Open Access Ref.no. [4])
focal solid mural thickening (*) at the left posterolateral
15.3.4 Urinary Bladder Fistulas carcinomas. Crohn’s disease (CD) represents the
most frequent cause of enterovesical fistulas
Fistulisation between the gastrointestinal and the (EVFs), particularly in young males, since the
urinary tract may underlie chronic or recurrent presence of the uterus and adnexa protects the
UTI, and the diagnosis is generally unsuspected bladder from penetration of full-thickness chronic
when pathognomonic symptoms such as pneuma- ileal inflammation. However, enterovesical fistulas
turia and faecaluria are absent. Most colovesical cause significant morbidity and generally mandate
fistulas (CVFs) develop secondary to sigmoid surgical repair to eradicate chronic urinary infec-
colon diverticulitis, occasionally from colorectal tion and prevent systemic sepsis [39–42].
15 Cross-Sectional Imaging of Urinary Bladder, Prostate and Seminal Vesicle Infections 165
Vesical fistulisation may be confirmed via oral Due to the usual heterogeneous enhancement
administration of indocyanine green dye or other of the prostate gland, CT provides little clue to
similar agents. Conversely, visualisation of the the presence of ongoing ABP, which may be sug-
fistulous track is generally challenging both at gested by rapid enlargement compared to previ-
cystoscopy (orifice is identified in less than 50% ous studies or coexistent signs of UTI in the
of cases) and imaging [39–42]. bladder or seminal vesicles (Fig. 15.11). Some
Since most patients with colonic diverticulitis, reports described MRI appearance of ABP as
colorectal cancer and CD are commonly investi- characterised by T2-hypointense “bands” with
gated with CT or MRI, radiologists should care- absent diffusion restriction and progressive or
fully seek for features consistent with vesical plateau enhancement, compared to the nodular
fistulisation. The presence of air in the bladder configuration, marked diffusion abnormality and
lumen without catheterisation or recent instru- “spike” enhancement of prostatic carcinoma
mentation is the commonest albeit indirect find- (PCa). Conversely, chronic prostatitis commonly
ing (Fig. 15.10a, b), but no air may be observed mimics PCa since it generally involves the
in the bladder if the patient has voided prior to the peripheral zone and shows low T2 signal inten-
examination. Other suggestive changes include sity, mild to moderate diffusion restriction corre-
retraction of the bladder wall, focal or diffuse sponding to increased cellular infiltrate and early
mural thickening, adhesion and tethering of and increased enhancement compared with nor-
thickened adjacent bowel loops. Fistulas are mal prostatic tissue. Despite these overlapping
directly identified only when filled by air, fluid or MRI features, diagnosis of chronic inflammation
enteral contrast (Fig. 15.10c, d). The extralumi- over PCA may be suggested by:
nal findings, such as bowel wall thickening,
diverticula or soft-tissue mass, generally hint to (a) Geographic configuration
the primary cause of the fistula [43–45]. (b) Lack of mass effect, contour deformity and
In our experience, CT-cystography proved to capsular alteration
be a fast, cheap and highly accurate modality to (c) Lower degree of diffusion restriction than in
depict CVFs and EVFs, since retrograde bladder PCa [3, 46]
distension opens and opacifies thin yet patent
fistulas (Fig. 15.10e, f). CT-cystography is rec- The key role of cross-sectional imaging is to
ommended after failed identification during cys- differentiate ABP from prostatic abscess (PA),
toscopy and CT, particularly when surgical which has similar clinical and laboratory features
treatment is to be planned [16]. but a different management. The latter generally
results from unrecognised or inappropriately
treated UTI or develops following recent tran-
15.4 Cross-Sectional Imaging srectal ultrasound (TRUS)-guided prostate
Appearances of Infections biopsy and often requires TRUS- or transperineal
of the Prostate and Seminal CT-guided drainage, sometimes surgical inci-
Vesicles sion. Interestingly, in prostatic infections an
increased serum prostate-specific antigen (PSA)
15.4.1 Prostatic Infections is common but generally regresses with therapy
[5, 8, 47, 48].
The widespread use of antibiotics has led to a TRUS may detect PAs as single or multiple
decline in the occurrence of UTIs involving both hypoechoic areas with thick walls, floating
the prostate and seminal vesicles. However, acute echogenic speckles in the cavity, and poorly
bacterial prostatitis (ABP) remains a relatively defined periphery with increased colour Doppler
common, potentially serious infection which is signals. Compared to TRUS, multiplanar CT
generally diagnosed on clinical grounds and provides a more comprehensive visualisation of
requires intensive parenteral antibiotic therapy [8]. PAs. The usual appearance is single, septated or
166 M. Tonolini
a b
c d
e f
Fig. 15.10 Three different cases of colovesical fistulas d) for an endoscopically impassable stricture, a fluid-filled
(CVFs). In an 88-year-old female with medically treated CVF (arrows) containing gas bubbles was directly identifi-
acute diverticulitis, contrast-enhanced multidetector CT able communicating with the thickened sigmoid colon (*).
revealed urinary bladder with some intraluminal gas (+ in A) Note minimal air in the bladder (+ in c) without previous
which was attributed to catheterisation (thick arrows) and instrumentation. In a 79-year-old woman with chronic UTI
thin urothelial hyperenhancement (thin arrow in a) consistent and previous CT demonstration of sigmoid colon diverticu-
with active UTI. On excretory phase acquisition (b), tip of losis and intravesical air, cystoscopy failed to detect fistulous
the Foley catheter (thick arrow) was seen protruding into the orifices. Additional CT-cystography (e, f) through the Foley
thickened diverticular sigmoid colon (*) through a CVF, catheter (thick arrow) showed leakage of diluted contrast in
which required surgical repair including segmental colic the sigmoid colon (*) through a short CVF (arrows), which
resection, colostomy and bladder suture. In a 78-year-old was surgically repaired (Partially reproduced from Open
female investigated with water enema CT colonography (c, Access Ref.no. [16])
15 Cross-Sectional Imaging of Urinary Bladder, Prostate and Seminal Vesicle Infections 167
a b
Fig. 15.11 An 80-year-old male was hospitalised because ceptible thin hyperenhancement along the prostatic ure-
of suspected urosepsis. As the sole acute abnormality, thra (thin arrows), without appreciable abscess cavities.
contrast-enhanced multidetector CT showed moderate Consistent clinical and laboratory findings confirmed the
enlargement of the prostate compared to a previous CT diagnosis of acute bacterial prostatitis
study (not shown), with heterogeneous structure and per-
a b c
d e f
Fig. 15.12 Prostatic abscess in a 48-year-old male with pelvic pain and enlarged tender prostate at digital rectal
perineal pain and abnormally increased CRP. Axial unen- examination. Multiplanar CT images (c–f) showed
hanced (a) and post-contrast (b) CT images showed mild marked prostatic enlargement by confluent nonenhancing
asymmetric prostatic enlargement occupied by a 4-cm hypoattenuating (17-19 HU) regions, with peripheral and
septated fluidlike collection (arrowheads) with peripheral septal enhancement (arrowheads). The prostatic infection
and septal enhancement. Note displacement of periure- involved also the left seminal vesicle (arrows in e, f), dis-
thral calcifications (thick arrows) from midline. placed upwards the urinary bladder with mild circumfer-
Ultrasound-guided transperineal drainage confirmed ential mural thickening and mucosal hyperenhancement
Escherichia coli infection. Another case of large prostatic (thin arrows) indicating UTI. The abscess was relieved by
abscess from ESBL-positive Escherichia coli infection in transperineal evacuation (Partially reproduced from Open
a 61-year-old male with previous chemo- and radiother- Access Ref.no. [4])
apy for non-Hodgkin lymphoma, fever (38 °C), dysuria,
15 Cross-Sectional Imaging of Urinary Bladder, Prostate and Seminal Vesicle Infections 169
a b
Fig. 15.13 Prostate carcinoma with post-treatment causing enlargement of the ipsilateral prostate gland, ini-
regressive (necrotic) changes in an 86-year-old elderly tially interpreted as an abscess. Note residual brachyther-
male with indwelling catheter (thick arrows). Axial (a) apy seed indicated by arrow in (b) (Reproduced from
and coronal (b) post-contrast CT images depicted a Open Access Ref.no. [4])
3 × 2 cm left-sided hypoenhancing region (arrowheads)
170 M. Tonolini
a b
c d
Fig. 15.14 Seminal vesicle abscess in a 74-year-old male (arrowheads) with thick, strongly enhancing walls and
with recurrent UTIs, suffering from malaise, persistent septa, speckled calcifications and internal liquefied areas.
fever, pelvic tenderness and dysuria. Transabdominal After intensive antibiotic treatment, the abscess partially
ultrasound (a) revealed a right paramedian inhomoge- decreased with disappearance of mass effect and of lique-
neous hypo-anechoic multiseptated mass (arrowhead), fied portions at follow-up CT (d). Serum prostate-specific
exerting compression on the urinary bladder. CT (b, c) agent (PSA) normalised from 10 to 5 ng/mL over 2 months
confirmed markedly enlarged right seminal vesicle (Reproduced from Open Access Ref.no. [4])
7. Browne RF, Zwirewich C, Torreggiani WC (2004) system: an imaging perspective. Insights Imaging
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172 M. Tonolini
Massimo Tonolini
Fig. 16.1 Uncomplicated acute urethritis in a 30-year- sequences (b, c). The infection did not interrupt the dartos
old male with neurogenic bladder treated by intermittent tunica and Buck’s fascia and did not involve the corpora
self-catheterization, manifesting with purulent urethral cavernosa, scrotum and ischioanal spaces. Note Foley
secretions and physical finding of induration and tender- catheter in place (thick arrows). The patient successfully
ness of the corpus spongiosum. MRI images revealed recovered with temporary suprapubic catheter and intra-
T2-weighted (a) diffuse, uniform hypersignal in the cor- venous and topical antibiotics [Reproduced with permis-
pus spongiosum (*) with corresponding intense homoge- sion from Open Access Ref.no [13]]
neous enhancement on post-gadolinium T1-weighted
(CM) were the mainstay techniques for imag- nosa and fibrous tunicae. The key differential diag-
ing the male urethra, particularly to assess trau- nosis is a urethral diverticulum, which is most
matic injuries and strictures: however, commonly located in the distal urethra and may
retrograde urethrography and voiding cystoure- closely resemble an abscess. Moreover, periure-
thrography could not assess the periurethral thral abscesses may further progress inferiorly
structures [4, 20, 21]. breaching through the Buck fascia, thus leading to
Conversely, nowadays the use of MRI can fasciitis and gangrenous necrosis of the subcutane-
effectively visualize periurethral abnormalities ous tissue of the perineum and scrotum (Fournier’s
[6, 13]. In our experience, uncomplicated acute gangrene) [7, 12, 13, 17].
urethritis may be seen as diffuse thickening of the In our experience, in patients with previous
penile urethra and surrounding corpus spongio- radical prostatectomy, persistent UTI may be
sum with intermediate-to-high signal intensity on complicated by pubic osteomyelitis through con-
T2-weighted images and corresponding intense tiguous spread of infection; therefore, in these
contrast enhancement (Fig. 16.1) [13, 17]. cases scrutinizing CT images with a bone win-
If untreated, urethritis may be complicated by a dow setting and comparison with previous stud-
periurethral abscess through infection of Littrè ies may be useful to appreciate irregularities and
glands. Since the penile tunica albuginea prevents erosions of the bony surfaces, cortical disconti-
the dorsal spread of infection, abscesses tends to nuity or frank osteolysis (Fig. 16.3).
track ventrally along the corpus spongiosum [14].
Periurethral abscesses may be also demon-
strated sonographically, but ultrasound is gener- 16.2.2 Funiculitis and Epididymitis
ally cumbersome due to inflammatory swelling
and tenderness of the penile and perineal struc- As mentioned above and extensively discussed
tures. MRI consistently visualizes penile abscesses in the appropriate chapter, ultrasound with
as fluid- or pus-filled cavities with enhancing colour Doppler rapidly supports a clinical and
periphery, typically located ventrally and in com- laboratory diagnosis of epididymo-orchitis.
munication with the urethra (Fig. 16.2), and may However, in our experience CT may occasion-
clearly depict the involvement of corpora caver- ally reveal signs of a clinically unsuspected
16 Cross-Sectional Imaging of Urethral, Penile and Scrotal Infections 175
Fig. 16.2 Penile and perineal abscess from progression on T2-weighted sequences (b–d) with surrounding
of urethral infection in a 53-year-old male with tender, inflammatory stranding (+), strong contrast enhancement
inflamed swelling despite antibiotic therapy. Perineal in the abscess walls (arrowheads in e, f). The infected cor-
infection was initially detected at contrast-enhanced CT pus spongiosum (*) showed similar signal features.
(a) as an elongated midline abscess with peripheral Surgical evacuation was required to relieve the abscess
enhancement (arrowheads) and internal fluid. MRI [Reproduced with permission from Open Access Ref. no
showed corresponding inhomogeneous fluid-like content [13]]
a b c
Fig. 16.3 Pubic osteomyelitis in a 78-year-old male with consistent with ongoing UTI in the venous phase (b), plus
history of radical prostatectomy and pelvic radiotherapy, a soft-tissue attenuation inflammatory tissue (+) extend-
suffering from recurrent urinary tract infections (UTIs). ing ventrally to surround the pubic symphysis. Note
CT urography showed a wide vertical opacified cavity metallic clips in (b). As seen with bone window settings
corresponding to the contracted urinary bladder, vesico- (c), the latter showed irregular erosions more pronounced
urethral anastomosis and proximal urethra (a). The con- on the left side (arrowhead) consistent with development
tracted bladder showed circumferential mural thickening of osteomyelitis, which was not present in a previous MRI
(*) and thin urothelial hyperenhancement (thin arrow) (not shown) and required intensive antibiotic therapy
176 M. Tonolini
a b
c d
Fig. 16.4 Unsuspected funiculitis and acute epididymitis pared to contralateral structure. Note Foley catheter (thick
in a 75-year-old male with persistent fever, acute urinary arrow in b). Subsequent colour Doppler ultrasound (d)
retention, pyuria, markedly increased leukocyte count and confirmed thickened hypoechoic ipsilateral epididymis
acute phase reactants. Contrast-enhanced CT (a–c) (thin arrows), particularly at the tail with increased flow
revealed asymmetric thickening and vascular engorge- signals consistent with acute inflammation. Despite nega-
ment of the right spermatic cord (arrowheads), enlarged tive cultures after empiric antibiotic therapy, levofloxacin
and hyperenhancing epididymis (thin arrow in c) com- effectively treated the infection
a b c
Fig. 16.5 Acute epididymo-orchitis in a 47-year-old Sri arrows) and testis (arrows). Note catheter (in a) and thick-
Lankan male with multiple myeloma on bortezomib ther- ened and increased oedematous attenuation of the scrotal
apy, suffering from fever and acute scrotal pain, tender- skin and external tunicae. Colour Doppler (c) revealed
ness and induration. Contrast-enhanced CT (a, b) hypervascularization of the epididymis (+). Unresponsive
performed to investigate impending urosepsis depicted a to antibiotics, this infection caused by Klebsiella pneu-
thickened engorged left spermatic cord, with inhomoge- moniae ultimately required orchiectomy [Reproduced
neous vascularization of the ipsilateral epididymis (thin with permission from Open Access Ref.no [13]]
a c d
e f g
Fig. 16.6 Surgically confirmed epididymo-orchitis with to contralateral structures and development of a large pos-
pyocele in a 72-year-old diabetic male with haematuria terior scrotal collection (§). Another surgically proven
and enlarged left scrotum, history of transurethral resec- case of testicular abscess and necrosis in a 59-year-old
tion of bladder carcinoma and bladder neck stricture male with epididymo-orchitis unresponsive to medical
treated by long-term catheterization (thick arrows). therapy: post-contrast CT (f, g) revealed vascular engorge-
Colour Doppler ultrasound revealed ipsilateral enlarged ment along the left spermatic cord (arrowhead), faintly
inhomogeneous epididymal head (+ in a) and hypervascu- enhanced epididymal head (thin arrow in e) and ipsilateral
larized testis (* in b). After ineffective antibiotic therapy, scrotum occupied by fluidlike collection (*) with thin
contrast-enhanced CT (c–e) showed hypervascularized peripheral enhancing rim [Partially reproduced with per-
left epididymis (thin arrows) and testis (arrows) compared mission from Open Access Ref.no [13]]
178 M. Tonolini
a b
Fig. 16.7 Surgically treated Fournier’s gangrene in a asymmetric left-sided thickening of the skin and subcuta-
63-year-old diabetic male with recurrent UTIs and peri- neous fat infiltration with presence of gas collections (*)
neal painful swelling. Unenhanced CT (a, b) revealed at the perineum and dorsal aspect of the scrotum
6–45% of patients and may be colorectal (such as the genital, perineal and gluteal regions with
tumour, diverticulitis, inflammatory bowel dis- unclear pathogenesis and chronic progressive
ease, perirectal abscess), urologic (lower UTI) or course, which is mostly encountered in black
cutaneous (e.g. pressure ulceration) in descend- people and males in association with poor
ing order of frequency [24, 25]. hygiene [27–29].
Multidetector CT is by far the preferred In our experience, MRI offers two key advan-
modality since it has higher specificity for the tages in this uncommon disorder: it accurately
diagnosis of FG and provides superior evaluation describes the affected regions, thus allowing
of disease extent. CT features include asymmet- optimal planning of wide excision and ultimately
ric fascial thickening, subcutaneous fat stranding a decreased recurrence rate, which is propor-
at the involved areas, superficial or deep fluid and tional to the radicality of surgery [27, 28]. On the
air-attenuation collections. Subcutaneous emphy- other hand, since skin inflammation, abscesses
sema produced by anaerobic bacteria is the hall- and fistulous tract are nonspecific physical mani-
mark of FG (Fig. 16.7); however, air is absent in festations, MRI may support a diagnosis of HS
up to 10% of cases. Furthermore, CT can define over epididymo-orchitis and scrotal abscess by
the starting point of the infectious process, demonstrating that tissue inflammation and
thereby allowing differentiation of complicated abscesses are confined to the skin and subcuta-
perineal infections from urinary versus an neous tissues, with a characteristic symmetric
alternative source, particularly cryptogenetic
distribution and lacking communication with
perianal sepsis (Fig. 16.8) [13, 24–26]. pelvic organ. Inflamed tissue and abscesses are
Another uncommon differential diagnosis of easily identified with MRI sequences acquired
perineal and scrotal infections is hidradenitis with fat suppression and after intravenous con-
suppurativa (HS), a rare inflammatory disease of trast (Fig. 16.9) [30].
180 M. Tonolini
a b
c d
Fig. 16.8 Extensive cryptogenetic perianal inflammation involving the right sphincter complex and obturator inter-
in a 56-year old diabetic male with fever. Axial post- nus (*) muscles and extending to the ischioanal fossa.
contrast CT image (a) revealed perineal abscess (arrow- Tiny abscess collections (arrows in b and c) were present.
heads) closely similar to that depicted in Fig. 16.2. Topography of infection, sparing of prostate and corpora
Additional MRI including axial STIR (b), post-gadolinium cavernosa and clinical examination were inconsistent
axial fat-suppressed (c) and coronal (d) T1-weighted with complicated UTI [Reproduced with permission from
images showed extensive inflammatory signal abnormali- Open Access Ref.no [13]]
ties and hyperenhancement (+) surrounding the anus,
16 Cross-Sectional Imaging of Urethral, Penile and Scrotal Infections 181
a b c
d e f
Fig. 16.9 Surgically confirmed hidradenitis suppurativa ening of the skin and subcutaneous planes with abnormal
in a 51-year-old male with hepatitis C, complaining of inflammatory signal intensity and hyperenhancement (+
progressive, painful swelling of perineum, scrotum and in e, f) involving the medial aspect of the thighs, perineal
penis, with thickened skin and fistulous orifices. Plain region and scrotum. Small purulent collections with
radiographs (a) excluded air collections in the swollen peripheral enhancement (arrowheads) and inflamed ingui-
scrotum. MRI including multiplanar T2-weighted (b–d), nal lymph nodes were present. The testes (not shown) did
post-gadolinium axial fat-suppressed (e) and coronal (f) not show appreciable abnormalities [Reproduced with
T1-weighted images depicted marked symmetrical thick- permission from Open Access Ref.no [13]]
14. Grabe M, Bartoletti R, Bjerklund-Johansen TE et al CT: a sign of epididymitis or testicular neoplasm.
(2014) Guidelines on urological infections. European Abdom Imaging 39:1014–1020
Association of Urology, The Netherlands. Available 23. Tonolini M (2016) Multidetector CT of expected
at: http://uroweb.org/wp-content/uploads/19-Urologi- findings and complications after contemporary
cal-infections_LR2.pdf. inguinal hernia repair surgery. Diagn Interv Radiol
15. Barozzi L, Valentino M, Menchi I et al (2010) Clinical 22(5):422–429
uroradiology: the standardisation of terminology for 24. Levenson RB, Singh AK, Novelline RA (2008)
lower urinary tract function and dysfunction. Radiol Fournier gangrene: role of imaging. Radiographics
Med 115:272–286 28:519–528
16.
Trojian TH, Lishnak TS, Heiman D (2009) 25. Piedra T, Ruiz E, Gonzalez FJ et al (2006) Fournier’s
Epididymitis and orchitis: an overview. Am Fam gangrene: a radiologic emergency. Abdom Imaging
Physician 79:583–587 31:500–502
17. Kubik-Huch RA, Hailemariam S, Hamm B (1999) 26. Khati NJ, Sondel Lewis N, Frazier AA et al (2015)
CT and MRI of the male genital tract: radiologic- CT of acute perianal abscesses and infected fis-
pathologic correlation. Eur Radiol 9:16–28 tulae: a pictorial essay. Emerg Radiol 22(3):
18. Browne RF, Zwirewich C, Torreggiani WC (2004) 329–335
Imaging of urinary tract infection in the adult. Eur 27. Alikhan A, Lynch PJ, Eisen DB (2009) Hidradenitis
Radiol 14(Suppl 3):E168–E183 suppurativa: a comprehensive review. J Am Acad
19. Yu M, Robinson K, Siegel C et al (2016) Complicated Dermatol 60:539–561. quiz 562–533
genitourinary tract infections and mimics. Curr Probl 28. Anderson BB, Cadogan CA, Gangadharam D (1982)
Diagn Radiol 46(1):74–83. https://doi.org/10.1067/j. Hidradenitis suppurativa of the perineum, scrotum,
cpradiol.2016.1002.1004 and gluteal area: presentation, complications, and
20. Kawashima A, Sandler CM, Wasserman NF et al
treatment. J Natl Med Assoc 74:999–1003
(2004) Imaging of urethral disease: a pictorial review. 29. Buimer MG, Wobbes T, Klinkenbijl JH (2009)
Radiographics 24(Suppl 1):S195–S216 Hidradenitis suppurativa. Br J Surg 96:350–360
21. Pavlica P, Barozzi L, Menchi I (2003) Imaging of 30. Kelly AM, Cronin P (2005) MRI features of hidrad-
male urethra. Eur Radiol 13:1583–1596 enitis suppurativa and review of the literature. AJR
22. Gupta SA, Horowitz JM, Bhalani SM et al (2014) Am J Roentgenol 185:1201–1204
Asymmetric spermatic cord vessel enhancement on
Part IV
Miscellaneous Topics
Cross-Sectional Imaging
of Urosepsis 17
Massimo Tonolini
far represents the ideal modality to comprehen- (32%) of patients, particularly hydro- or pyone-
sively investigate severe UTI and possible com- phrosis (17%) and urolithiasis (7.6%). Other find-
plications [4–10]. ings in descending order or frequency included
Figures 17.1, 17.2, and 17.3 present three clin- tumours, renal abscesses, ureteral dilatation, caly-
ical examples of cross-sectional imaging investi- ceal dilatation, duplex kidney, ureteral structure,
gation of urinary sepsis. In our experience, the infected polycystic kidney, emphysematous pyelo-
use of CT is particularly useful in the postopera- nephritis and displaced nephrostomy. Clinical pre-
tive setting after urological instrumentation and dictors of major abnormalities include increased
surgery [9, 11–13]. serum creatinine, type 2 diabetes, diabetic compli-
In a large study including 221 adult patients cations, known renal disease or urological abnor-
experiencing first-time urosepsis, the use of CT mality. Interestingly, abnormal CT findings led to
discovered major findings in almost one-third urological intervention in approximately one-half
Fig. 17.1 A 71-year-old female with a congenital soli- the bladder (thin arrow in d; note Foley catheter indicated
tary kidney was hospitalized for voiding difficulty and by thick arrow). Findings were consistent with diagnosis
high fever unresponsive to empirical antibiotics. Urgent of urosepsis which required prolonged in-hospital treat-
unenhanced (a) and post-contrast (b–d) multidetector CT ment. Four months after discharge, repeated CT (e, f)
revealed mild hydronephrosis with preserved renal func- showed decreased hydronephrosis, normalized mural
tion. The dilated renal pelvis (*) showed minimal, enhanc- thickening and disappearance of urothelial hyperenhance-
ing mural thickening (thin arrows in b) which was even ment. Note absent left kidney
more pronounced along the ureter (thin arrow in c) and in
17 Cross-Sectional Imaging of Urosepsis 187
Fig. 17.2 A 41-year-old female immigrant from the progressively improved with medical therapy. Urine cul-
Middle East had history of renal colic 2 years ago. tures diagnosed Escherichia coli infection. Before dis-
Currently attended at emergency department for abdomi- charge, repeated CT (c, d) showed resolution of
nal and right flank pain associated with shivers, high fever parenchymal changes and persistence of calyceal dilata-
and dysuria. Laboratory tests revealed leukocytosis and tion (arrow) and of pelvic urothelial enhancement (thin
increased acute phase reactants. Urgent contrast-enhanced arrows). Distant follow-up CT (e, f) showed resolved
CT (a, b) showed mild, hyperenhancing thickening of the hydronephrosis and urothelial enhancement and persistent
renal pelvis (thin arrows), calyceal dilatation (arrow) at upper calyceal dilatation (arrows) with focal thinning of
the upper renal third, two wedge-shaped hypoperfused the overlying parenchyma consistent with chronic
parenchymal areas (*), consistent with right acute pyelitis “scarring”
and pyelonephritis. Transferred to intensive care unit, she
of cases, such as positioning or replacement of are most usually found in the lungs, the brain, the
nephrostomy or ureteral stent, sometimes cyst liver and spleen and the iliopsoas muscles [14].
drainage, catheter replacement, stone removal and Finally, as exemplified in Figs. 17.1, 17.2, and
occasionally even nephrectomy [3]. 17.3, cross-sectional CT imaging is highly valu-
Furthermore, multidetector CT provides pan- able to provide consistent follow-up of severe or
oramic body exploration, thus allowing to detect complicated UTIs during medical or interven-
infectious changes resulting from haematogenous tional therapy, in order to document resolution of
dissemination in other anatomical regions, which infectious changes or long-term sequelae [5–8].
188 M. Tonolini
Fig. 17.3 A 61-year-old male with recent radical cystec- arrows). Pyonephrosis was relieved by ureteral stenting
tomy for bladder carcinoma and orthotopic neobladder (§) (thick arrows) as seen on repeated unenhanced CT (c, d)
reconstruction, as documented by postoperative multide- with resolution of perirenal inflammation and persistently
tector CT urography. Note right-sided hydronephrosis (*) thickened posterior renal fascia (thin arrow in d). With
with delayed contrast excretion. A year later, he was hos- resolution of urosepsis and improved renal function, fol-
pitalized for sepsis and acute renal failure. Unenhanced low-up contrast-enhanced CT (e, f) showed resolution of
CT (b) showed stable dilatation of the right renal pelvis infectious changes, preserved nephrographic effect, stable
(*) with appearance of peripelvic and perirenal “fat hydronephrosis (*) compared to (a) and well-distended
stranding” (+) and of ipsilateral fascial thickening (thin neobladder (§)
11. Tonolini M, Ierardi AM, Varca V et al (2015) 13. Tonolini M, Villa F, Bianco R (2013) Multidetector CT
Multidetector CT imaging of complications after lap- imaging of post-robot-assisted laparoscopic radical pros-
aroscopic nephron-sparing surgery. Insights Imaging tatectomy complications. Insights Imaging 4:711–721
6:465–478 14. Tonolini M, Campari A, Bianco R (2012) Common
12. Tonolini M, Villa F, Ippolito S et al (2014) Cross- and unusual diseases involving the iliopsoas muscle
sectional imaging of iatrogenic complications after compartment: spectrum of cross-sectional imaging
extracorporeal and endourological treatment of uro- findings. Abdom Imaging 37:118–139
lithiasis. Insights Imaging 5:677–689
Modern Imaging of Urogenital
Tuberculosis 18
Massimo Tonolini
M. Tonolini, M.D.
Radiology Department, “Luigi Sacco” University
Hospital, Via G.B. Grassi 74, Milan 20157, Italy
e-mail: mtonolini@sirm.org
a b c d
e f g
Fig. 18.1 An 82-year-old male was diagnosed with lum- tion (d) did not reveal urinary tract calcifications. The
bar spondylodiscitis on the basis of characteristic mild urothelial thickening along the right renal pelvis and
inflammatory-type MR signal changes affecting the L4 ureter (thick arrows) showed positive contrast enhance-
and L5 vertebral bodies (T1-weighted a, short-tau inver- ment (e). The atrophied right kidney had uneven calyceal
sion recovery b, T2-weighted c) and abscessualized inter- dilatation (thin arrows in e). The left-sided hydronephro-
vertebral disc (arrows in b, c). The hypothesis of spinal sis (* in e) was confirmed, with preserved nephrographic
tuberculosis was suggested by the presence of bilateral phase and contrast excretion, and secondary to a short
paravertebral abscesses (+ in c). Incidental findings stricture of the distal ureter (arrowheads in delayed phase
included moderate left-sided hydronephrosis (*), right images f and g). Tuberculosis was confirmed by positive
kidney with parenchymal thinning, dilated and distorted QuantiFERON assay and vertebral biopsy and improved
calyces (thin arrows) and non-dilated pelvis with some after specific combined therapy (Adapted from Open
mural thickening (thick arrow). Unenhanced CT acquisi- Access Ref.no [21])
194 M. Tonolini
a b c
d e f
Fig. 18.2 An 80-year-old male being investigated for were well visible on CT including preliminary unen-
reasons unrelated to the urinary tract had sonographic hanced scan (d). After intravenous contrast, nephro-
detection of a hypo-anechoic upper pole lesion (calipres) graphic (e) acquisition confirmed left upper renal pole
of the left kidney, mostly occupied by a large calcification with thinned parenchyma and dilated and distorted caly-
causing posterior acoustic shadowing. Coronal (b) and ces opacified by urine in the delayed excretory (f) phase.
fat-saturated axial (c) T2-weighted images from MR chol- An additional focal renal scarring with calcification was
angiopancreatography depicted very low-signal structures noted (thick arrow). Findings were consistent with chronic
(arrowheads) suggestive of calcifications, located within tubercular infection, without appreciable abnormalities of
dilated calyces (thin arrows). Calcifications (arrowheads) the excretory tract and bladder
a b
Fig. 18.3 A 14-year-old adolescent boy immigrated The kidneys and collecting system did not show signifi-
from Eastern Europe suffered from persistent dysuria and cant abnormalities; the ureters were not dilated.
macroscopic haematuria. Transverse (a) and longitudinal Cystoscopy confirmed extensive, severe inflammatory
(b) ultrasound images showed normally distended urinary changes of the bladder wall. Diagnosis of urinary tubercu-
bladder with circumferential mural thickening (*), partic- losis was ultimately made, after negative urinary tests and
ularly severe on the right posterolateral and upper aspects. cultures
a b c
d e f
Fig. 18.4 A 58-year-old woman was transferred from thick, strongly enhancing endometrium (thin arrows).
Albania under presumptive diagnosis of ovarian carci- Consultation with attending gynaecologist diagnosed
noma including increased serum CA125 tumour marker. bilateral tubo-ovarian abscesses and pyometra. After
A year earlier, her husband was diagnosed affected with inconclusive microbiological assays, endometrial wash-
lung tuberculosis. Contrast-enhanced body CT revealed ing and biopsy yielded purulent necrotic material with
several centimetric non-calcified and non-cavitary pulmo- epithelioid giant cell granulomas, without micro-
nary nodules (a), particularly at both apical regions; organisms at microscopy and culture. Genital tuberculosis
necrotic mediastinal adenopathies (arrowhead in b); bilat- was confirmed by positive QuantiFERON test and poly-
eral adnexal enlargement from pear-shaped fluid collec- merase chain reaction for mycobacterial DNA (Adapted
tions (+) with thin, minimally irregular enhancing from Open Access Ref.no [25])
periphery; dilatation of the uterine cavity (*) lined by
(Fig. 18.4) which are easily confused with pyo- nary tract infection (“sterile pyuria”) and
genic tubo-ovarian abscesses and even ovarian prostatic, epididymal or adnexal lesions, par-
tumours [13, 24, 25]. ticularly in immigrants from endemic areas
or immunosuppressed such as HIV-positive
Conclusion patients [2, 4].
Recognition of UG-TB is important since Cross-sectional imaging, particularly with
if left untreated, it leads to shrunken, non- multidetector CT, comprehensively evaluates
functioning kidneys. However, it is usually a the entire urogenital tract and consistently
challenging clinical diagnosis due to subtle, supports the diagnosis of UG-TB particularly
unspecific symptoms and time-consuming, when a combination of multiple findings is
difficult cultures. Albeit the majority of cases observed. Table 18.1 summarizes the early
occur in the Third World, UG-TB is occasion- and late urinary changes which should alert
ally but increasingly encountered in Western the radiologist to the possibility of tuberculo-
countries and should be suspected in patients sis, particularly if multiple and bilateral [11,
with unexplained haematuria, resistant uri- 12, 20].
18 Modern Imaging of Urogenital Tuberculosis 197
Table 18.1 Early and advanced cross-sectional imaging 9. Vanhoenacker FM, De Backer AI, Op de BB et al
features suggesting urinary tuberculosis, particularly if (2004) Imaging of gastrointestinal and abdominal
multiple and bilateral (Reproduced from Open Access tuberculosis. Eur Radiol 14(Suppl 3):E103–E115
Ref.no [21]) 10. Harisinghani MG, McLoud TC, Shepard JA et al
(2000) Tuberculosis from head to toe. Radiographics
Early • Renal low-attenuation, hypoperfused
20:449–470. quiz 528-449, 532
changes parenchymal regions with or without
11. Zissin R, Gayer G, Chowers M et al (2001)
abscess-like collections
Computerized tomography findings of abdominal
• Uneven pelvicalyceal dilatation tuberculosis: report of 19 cases. Isr Med Assoc J
and/or distortion, particularly 3:414–418
caliectasis without pelvic 12. Engin G, Acunas B, Acunas G et al (2000) Imaging
dilatation of extrapulmonary tuberculosis. Radiographics 20:
Advanced • Variably distributed renal 471–488. quiz 529-430, 532
changes calcifications 13. Turkmen IC, Bassullu N, Comunoglu C et al (2012)
• Diffuse renal scarring and Female genital system tuberculosis: a retrospective
atrophy clinicopathological study of 1,548 cases in Turkish
• Replacement of kidney by women. Arch Gynecol Obstet 286:379–384
cavities communicating with the 14. Lee JY, Park HY, Park SY et al (2011) Clinical char-
collecting systems acteristics of genitourinary tuberculosis during a
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• Hydronephrosis and/or poorly tomography versus excretory urography: through 46
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obstructing calculi 16.
Merchant S, Bharati A, Merchant N (2013)
• Contracted thickened urinary Tuberculosis of the genitourinary system-urinary
bladder tract tuberculosis: renal tuberculosis-part II. Indian J
Radiol Imaging 23:64–77
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Merchant S, Bharati A, Merchant N (2013)
Tuberculosis of the genitourinary system-urinary tract
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Imaging Infections
in Transplanted Kidneys 19
Stefano Palmucci, Pietro Valerio Foti,
and Massimiliano Veroux
19.1 Imaging Infections In the first week, early infections are usually
in Transplanted Kidneys represented by pneumonia, surgical wound infec-
tions, urinary tract infections, vascular access infec-
Infections are common in renal transplant recipi- tion, and Clostridium difficile colitis. From the 1st
ents, with more than 80% of infections develop- to 6th month, intermediate infections are caused
ing in the first year after transplantation [1]. They by opportunistic agents or Cytomegalovirus: in this
still represent a cause of rejection in transplant period, surgical site infections or reactivations of
patients, even if technical advances in surgery dormant host infections [6] may be observed.
and immunosuppressive treatment have reduced
the failure rate of renal grafts. The optimization
of immunosuppressive therapy has diminished 19.1.1 Imaging Techniques
the percentage of rejection but at the same time
has increased the risk of renal infection [2, 3]. In the evaluation of infective diseases in trans-
Infections may be reported in renal and extra- planted kidneys, two main topics need to be
renal locations [1]; in addition, as reported by addressed in more detail:
Akbar et al., they may be distinguished on the
basis of the timing of their appearances: 1. Firstly, kidney transplant recipients are often
represented by immunocompromised subjects.
1 . Infections that occur in the first week This means that infections develop with a dif-
2. Infections that develop from the 1st month to ferent clinical course from healthy people.
6th months after transplantation 2. Secondly, transplanted kidneys should be inves-
3. Infections from 6 months onward tigated avoiding the use of contrast-enhancing
techniques, because iodinate contrasts or gado-
These infections are schematically classified linium agents are nephrotoxic; kidney transplant
as early, intermediate, and late infections [4, 5]. recipients, particularly when involved with
infections, may have impaired renal function • Conventional T2-weighted single-shot Fast
and reduced creatinine clearance. Therefore, Spin-Echo (FSE) sequence, acquired with
radiologists should carefully evaluate the risk of large Field Of View (FOV), covering from L2
contrast-associated nephropathy. to the perineum.
• Axial and coronal T2-weighted fast recovery
Based on previous considerations, UltraSonog- FSE sequences, with FOV limited to pelvis,
raphy (US) is routinely performed as first imag- acquired from the upper portion of trans-
ing modality [7]: it can safely investigate patients planted kidney to the perineum; sequences
avoiding ionizing radiation exposure. It provides may be repeated with spatial fat saturation.
also functional information—thanks to differ- • Axial T1-weighted FSE sequence, acquired
ent Doppler sonographic indexes. Multidetector with the same space orientation and extension
Computed Tomography (MDCT) could be used of axial T2-weighted sequences.
as second-step imaging modality: it has excel- • Diffusion-weighted sequences, using multiple
lent spatial resolution, even if performed without b-values (from 0 to 800); if a b multi-fitting is
contrast agent. However, unenhanced scans have not allowed, a couple of b-values (0 and 800
some limitations, mainly represented by poor con- and/or 0 and 500) are used.
trast resolution for the detection and characteriza-
tion of focal lesions in transplanted kidneys. Functional sequences need to be positioned
Magnetic Resonance (MR), thanks to its great with the same orientation of morphological axial
contrast resolution, shows high accuracy in the T1 and T2 sequences, in order to provide high cor-
characterization of renal and extrarenal lesions, relation of altered signal areas; diffusion sequences
providing information about the content (blood, may be also performed on a coronal plane.
serous, proteinaceous material). In the past, it has
been considered a very important diagnostic tool
in the assessment of transplanted renal compli- 19.1.2 Urinary Tract Infections
cations: indeed, gadolinium agents were consid-
ered safe, without risk of nephrotoxicity. MR was Urinary Tract Infection (UTI) occurs in >75%
considered as the gold standard for the evaluation in kidney transplant recipients [12]. It has been
of vascular and nonvascular complications in kid- described as the most common infective compli-
ney transplant recipients. cation after kidney transplantation [13].
Since 2006, several articles have reported in UTIs represent the most common bacterial
literature that the risk of Nephrogenic Systemic infections that require hospitalization in kidney
Fibrosis (NSF) in subjects with impaired renal transplant recipients: they occur more frequently
function [8] and contrast-enhanced MR has been than pneumonia, postoperative infections, and
discounted. septicemia [14].
Recently, functional evaluation has been In the management of renal transplant recipi-
gradually introduced into the MR protocol for ents, several critical problems may be associated
characterization of focal renal lesions: Diffusion- with UTI: the interaction between antibiotic treat-
Weighted Imaging (DWI) and Diffusion Tensor ments and immunosuppression agents, the devel-
Imaging (DTI) have been used in several stud- opment of resistant bacteria, and the high tendency
ies to assess renal function and characterize renal for recurrence in transplanted kidneys [12].
lesions [9–11]. Several causes and risk factors have been
An MR protocol should include not only mor- identified in the pathogenesis of UTI: pretrans-
phological sequences but also functional acquisi- plant UTI, prolonged period of hemodialysis
tions for the evaluation of transplanted kidneys. before hospitalization, polycystic kidney disease,
On the basis of previous studies published in lit- diabetes mellitus, urinary catheterization, immu-
erature [9, 11], the following sequences are gen- nosuppression, allograft trauma, and technical
erally acquired: complications related to ureteral anastomosis
19 Imaging Infections in Transplanted Kidneys 201
a b
Fig. 19.1 A 55-year-old woman with pyelonephritis ADC map (b), lesions show mild to moderate signal
affecting transplanted kidney. On diffusion sequences (a), restriction. The clinical features—fever and right iliac
PN areas appear as triangle-shaped hyperintense lesions pain—and the MR reports suggested the diagnosis of uri-
(white arrow posteriorly and dashed arrow anteriorly); on nary infection
[15]; in addition, predisposing factors include multiple focal areas of pyelonephritis are present
female gender, age, urinary tract abnormalities, in the renal parenchyma. A differential diagno-
and organ from deceased donor [12]. sis includes acute rejection [17], which is char-
The impact of UTI on allograft function has acterized by organ enlargement, swelling of the
been investigated with several parameters— medullar pyramids, loss of cortico-medullary dif-
such as iothalamate Glomerular Filtration Rate ferentiation, and edema in the renal sinus fat [18].
(iGFR), estimated Glomerular Filtration Rate MR examinations are very helpful in the assess-
(eGFR), and creatinine value [16]. However, ment of renal infection in kidney transplant recipi-
variations of these parameters are controversial; ents. PNs may be demonstrated as areas with
in one study published by Giessing et al., mea- hypointense signal on T1-weighted acquisitions
surements of creatinine values and eGFR were and hyperintense signal on T2-weighted acquisi-
not statistically different between transplanted tions. Currently, morphological T1-weighted and/
kidneys with and without UTI [12]; the iGFR or T2-weighted sequences are combined with DWI
values were different between the two groups. [19, 20], providing a more accurate diagnosis of
Clinically, UTIs are associated with bacteremia infection in renal parenchyma (Fig. 19.1). It may
and fever, which is reported in approximately half of also help radiologists in the differential diagnosis
patients [6]. Patients may also present not only with between acute and chronic processes in the renal
classic UTI symptoms but also with gastrointestinal parenchyma.
alterations or asymptomatic bacteriuria [14]. In a recent paper by Henninger et al., DWI has
In most cases, UTIs are represented by pyelo- been investigated for the assessment of nephritis
nephritis, renal abscesses, and peritransplant [19]. In this study, T1-weighted and T2-weighted
abscesses. sequences were compared to DWI for the pres-
On ultrasonography, pyelonephritis (PN) ence of regions with altered signal in renal paren-
may involve renal parenchyma in a focal or dif- chyma. DWI sequences demonstrated with high
fuse pattern. Focal PN is depicted as a small area accuracy pathological areas in all 21 patients with
of increased or decreased echogenicity. This infection, whereas conventional T2-weighted
sonographic pattern is not specific, mostly when acquisitions were able to demonstrate “obvious”
202 S. Palmucci et al.
a b c
Fig. 19.2 Axial T2-weighted images (without and with show increased thickness of ureteral wall; moderate
spatial fat saturation, respectively, on a and b) and DWI hyperintensity is also depicted along the course of the ure-
sequence (c) show ureter inflammation signs in right iliac ter, due to inflammation (white arrows)
fossa, occurring in a 54-year-old woman. Figures clearly
abnormal signal in 3 out of 21 patients and by renal enlargement and perivisceral fluid col-
“slightly pathological signal” in 17 out of 21 sub- lections. In some cases, small hypo-attenuated
jects [19]. In one patient, T2-weighted sequences areas may be detected in the renal parenchyma,
did not reveal abnormal signal on renal paren- but they may overlap with renal infarction or
chyma. Based on these results, authors declared cortical cyst. Thickened borders are usually
that “DWI of the kidneys seems to be highly sen- associated with infections or abscesses and no
sitive for the detection of infections within the with infarcted areas.
kidney” [19]. Peritransplant abscesses are uncommon and
PNs—in a focal or diffuse pattern—should occur after the first week (Fig. 19.3). These
be differentiated from renal infarction, which abscesses could be due to extrarenal extension
appears as wedge-shaped triangular area with of pyelonephritis; they may be also caused by
no perfusion on color Doppler. The identifica- colonization of bacterial in fluid collections as
tion of other extrarenal imaging features may urinoma, lymphocele, and hematoma.
be helpful in obtaining a differential diagno- A peritransplant abscess should be differenti-
sis. Indeed, the ureteral wall thickening may be ated from lymphocele, which is a fluid collection
another feature commonly detected on US or without epithelial border; on US, typical imaging
MR examinations, suggesting an infective dis- features of lymphocele are represented by a vari-
ease (Fig. 19.2). able in size anechoic area, often with lobulated
The presence of a variable echogenicity shape, without borders (Fig. 19.4). Lymphocele
inside a dilated pyelocaliceal system is clini- is clearly depicted as a fluid water-density collec-
cally significant for pyonephrosis [17]; the pres- tion on CT images (Fig. 19.5); on MR sequences,
ence of gas in the renal parenchyma is typical it appears as a fluid collection with homoge-
of emphysematous pyelonephritis [17], which neous high signal on T2-weighted acquisitions
could be also found as complication of a normal and hypointense signal on T1-weighted images
renal infection. (Fig. 19.5). No restriction signal is observed on
CT may be limited in the diagnosis of UTI: functional imaging.
unenhanced scans, very often acquired to pre- Hematomas may also occur as peritransplant
vent renal damage from iodinate contrast, are fluid collection: an intralesional fluid-fluid
able to provide nonspecific signs, represented level—depicted on sonographic images—may
19 Imaging Infections in Transplanted Kidneys 203
Conclusion
Infections of transplant renal recipients are
commonly detected in the posttransplant
period. Imaging plays a crucial role in the
detection of renal and extrarenal infections;
b very often, it has to provide a correct diagno-
sis in infected organs with impaired renal
function, which limits the utilization of con-
trast agent.
References
1. Akbar SA, Jafri SZ, Amendola MA, Madrazo BL,
Salem R, Bis KG (2005) Complications of renal trans-
plantation. Radiographics 25(5):1335–1356
2. Fishman JA, Rubin RH (1998) Medical progress:
Fig. 19.5 A 61-year-old woman with transplanted kidney infection in organ transplant recipients. N Engl J Med
in left iliac region (white asterisk). A large fluid collection 338:1741–1751
is demonstrated on CT and MR images (a and b, respec- 3. Sia IG, Paya CV (1998) Infectious complications
tively); the lesion is homogeneous hypodense on CT (white following renal transplantation. Surg Clin North Am
arrow in a) and hyperintense on MR (white arrow in b) 78:95–112
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4. Fishman JA (2007) Infection in solid-organ transplant 13. Castañeda DA, León K, Martín R, López L, Pérez H,
recipients. N Engl J Med 357:2601–2614 Lozano E (2013) Urinary tract infection and kidney
5. Tanphaichitr NT, Brennan DC (2000) Infectious com- transplantation: a review of diagnosis, causes, and cur-
plications in renal transplant recipients. Adv Ren rent clinical approach. Transplant Proc 45:1590–1592.
Replace Ther 7:131–146 https://doi.org/10.1016/j.transproceed.2013.01.014
6. http://www.emdocs.net/transplant-emergencies-part- 14. Karuthu S, Blumberg EA (2012) Common infec-
i-infection-rejection-and-medication-effects/ tions in kidney transplant recipients. Clin J Am Soc
7. Sharfuddin A (2014) Renal relevant radiology: imag- Nephrol 7:2058–2070
ing in kidney transplantation. Clin J Am Soc Nephrol 15. Muñoz P (2001) Management of Urinary Tract
9:416–429 Infections and Lymphocele in renal transplant recipi-
8. Thomsen HS, Morcos SK, Dawson P (2006) Is there a ents. Clin Infect Dis 33(Suppl 1):S53–S57. Review
causal relation between the administration of gadolinium 16. Ariza-Heredia EJ, Beam EN, Lesnick TG, Cosio FG,
based contrast media and the development of nephro- Kremers WK, Razonable RR (2014) Impact of uri-
genic systemic fibrosis (NSF)? Clin Radiol 61:905–906 nary tract infection on allograft function after kidney
9. Palmucci S, Mauro LA, Failla G, Foti PV, Milone P, transplantation. Clin Transpl 28:683–690. https://doi.
Sinagra N, Zerbo D, Veroux P, Ettorre GC, Veroux org/10.1111/ctr.12366
M (2015) Magnetic resonance with diffusion- 17. Kolofousi C, Stefanidis K, Cokkinos DD, Karakitsos
weighted imaging in the evaluation of transplanted D, Antypa E, Piperopoulos P (2012) Ultrasonographic
kidneys: updating results in 35 patients. Transplant features of kidney transplants and their complica-
Proc 44:1884–1888. https://doi.org/10.1016/j.trans tions: an imaging review. ISRN Radiol 2013:480862.
proceed.2012.06.045 https://doi.org/10.5402/2013/480862. eCollection
10. Erbay G, Koc Z, Karadeli E, Kuzgunbay B, Goren 2013
MR, Bal N (2012) Evaluation of malignant and benign 18. Al-Khulaifat S (2008) Evaluation of a transplanted
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org/10.1258/ar.2011.110601 19. Henninger B, Reichert M, Haneder S, Schoenberg
11. Palmucci S, Cappello G, Attinà G, Foti PV, Siverino SO, Michaely HJ (2013) Value of diffusion-weighted
RO, Roccasalva F, Piccoli M, Sinagra N, Milone P, MR imaging for the detection of nephritis. Sci World
Veroux M, Ettorre GC (2015) Diffusion weighted J 2013:348105. https://doi.org/10.1155/2013/348105
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org/10.1016/j.aju.2012.01.005
Interventional Radiology
for Drainage of Urine 20
Anna Maria Ierardi, Salvatore Alessio Angileri,
Enrico Maria Fumarola, and Gianpaolo Carrafiello
20.3.1 Fluoroscopic Guidance is aligned with the calix in this view, the operator
should be able to aspirate urine from the collecting
Fluoroscopically guided percutaneous access system, confirming proper positioning [12].
requires opacification of the renal collecting
system. Most commonly radiographic contrast
medium is instilled via cystoscopically placed 20.3.2 Ultrasound Guidance
ureteral catheters. The side which needs to be
treated is slightly elevated on a foam pad, a In recent years, ultrasonography has emerged as
maneuver that brings the posterior calices into an adjunct imaging modality to reduce time and
a more vertical position. The neck of the patient radiation exposure, without compromising the
is placed in a neutral position with a chest roll success of the procedure [13].
positioned to facilitate ventilation. The upper Doppler technology represents another advan-
extremity ipsilateral to the affected kidney is tage and can help to visualize and to avoid renal
placed at 90-degree flexion, and the contralateral blood vessels during percutaneous puncture [14].
upper extremity is tucked at the side to allow the A direct approach to the kidney, likewise to
C-arm to be positioned as close to the patient vascular procedures, can be obtained with the
as possible. Biplanar fluoroscopy is the most Seldinger technique. The Seldinger technique
commonly used imaging method. Radiographic involves an ultrasound-guided puncture of the col-
guidance of needle puncture into the collecting lecting system with a sheathed 18-gauge needle.
system for anterograde percutaneous access is US guidance permits visualization of the needle
routinely performed using one of two techniques, from the skin entrance site to the target renal calyx
including eye of the needle and triangulation. (Fig. 20.1). After injection of a small amount of
With the C-arm in the 30-degree position, an iodinated contrast medium to opacify the cavity,
18-gauge diamond tip access needle is positioned, under fluoroscopy, an hydrophilic guidewire can
so that the targeted calix, needle tip, and needle be inserted and, upon this wire, advanced the nee-
hub are in line with the image intensifier, giving a dle sheath. Lastly, the hydrophilic wire is replaced
bull’s-eye effect on the monitor. with a super-stiff guidewire to insert, usually, a
Continuous fluoroscopic monitoring is per- pigtail catheter (Fig. 20.2) [15].
formed to ensure that the needle maintains the proper Constraining the access trajectory to the pos-
trajectory. Needle depth is ascertained by rotating terolateral aspect of the kidney can create an
the C-arm to a vertical orientation. If the needle undesirable geometry resulting in the catheter
a b
Fig. 20.1 (a) Preliminary ultrasound examination per- fies the kidney (cortex, pelvis, and ureter): the white line
mits to visualize the kidney and to plan the path of the indicates the path of percutaneous access
percutaneous access. (b) Sagittal ultrasound image identi-
210 A.M. Ierardi et al.
a b c d
Fig. 20.2 (a) Through the needle, an injection of a small can be inserted. (c) The hydrophilic wire is replaced with
amount of iodinated contrast medium permits to opacify a super-stiff guidewire. (d) A pigtail catheter is correctly
the cavity. (b) Under fluoroscopy, a hydrophilic guidewire deployed
exiting posteriorly. Instead, for patient comfort, even because, although the collecting system
a more lateral approach that allows the patient to may be completely decompressed, many of
rest comfortably in a supine position is preferred. these patients will have chronically dilated renal
Collection of a sample for urine culture may collecting systems due to prior ureteral obstruc-
be obtained when access to the collecting system tion [17].
has been established. Sometimes, a central puncture may be per-
A sample of urine for culture may be useful formed more easily, but a drainage can’t be
when [3]: deployed; therefore, once the collecting system
is opacified, a second needle can be guided under
1. There is clinical suspicion of urinary tract
fluoroscopy into a more suitably peripheral calyx.
infection. It is important to remember that in the prone
2. If there is an indwelling or recently removed position, contrast material pools dependently in
stent or hardware. anterior calices. Once needle position within the
3. Patients have an ureteroenteric anastomosis. collecting system is confirmed, visualization of
posterior (antidependent) calices can be accom-
plished by injection of several milliliter room air
20.3.3 Percutaneous Access into the collecting system [17].
of Nondilated Renal Another option for accessing a nondilated
Collecting System collecting system is to use a 21-gauge needle to
access the renal pelvis under US guidance; this
These procedures are often relatively difficult to needle can then be used to opacify the collecting
perform for two reasons: first, the renal collecting system, and a second needle (e.g., greater than
systems are typically completely decompressed 18G) can be advanced into a target calyx under
due to the leak; second, many of these patients fluoroscopy [10].
have recently undergone a significant operation CT-guided access may also be described, par-
via a ventral approach, making patient position- ticularly when selection of a specific calyx is
ing difficult [10]. critical [18].
Different techniques may be used [16]. Another technique to access to a nondilated
The first choice should always be ultrasound collecting system is similar to the way a nondi-
(US), given its low risk and ready accessibility, lated biliary tree is accessed: a small needle is
20 Interventional Radiology for Drainage of Urine 211
advanced into the kidney under US or fluoro- commonly used by interventional radiologists for
scopic observation, and then during slow retrac- urinary drainage.
tion with gentle aspiration, the operator observes
the needle hub for the appearance of urine.
Contrast material is then injected to evaluate the 20.4.1 External Devices:
position. Alternately, following needle placement, Nephrostomy
gentle injection of contrast can be performed as
the needle is retracted, taking care not to create Pigtail catheter positioned in the renal pelvis pro-
large contrast stains in the parenchyma by alter- vide obligatory external drainage for ipsilateral
nating gentle injection and aspiration [19]. obstruction and for external diversion of urine for
If these techniques are not successful and patients with ureteral or bladder injury or leak.
there is no contraindication, the intravenous (IV) Patients with neurogenic bladder or chronic blad-
administration of approximately 50–80 mL of der outlet obstruction may be managed with a
iodinated contrast can be helpful to visualize the transurethral Foley catheter or a suprapubic cys-
renal collecting system [17]. tostomy locking loop catheter placed percutane-
Once acceptable needle access to the urinary ously into the urinary bladder from the anterior
system has been established, a wire is advanced abdominal wall [20].
through the needle into the collecting system. After placement, routine exchange of nephros-
It is unimportant whether the wire passes down tomy catheters is required to prevent encrustation
the ureter or loops within an upper pole calyx, and subsequent infections. Patients are typically
so long as there is a portion of stiff wire in the scheduled for exchange at 8–10-week intervals;
collecting system adequate to support exchange replacement should be anticipated if signs or
for a coaxial introducer. When advancing the symptoms of tube obstruction or malposition
coaxial dilator, care should be taken not to trau- occur. Signs of obstruction include any combina-
matize the urothelium with the guidewire or tion of fever, flank pain, any malfunctions of the
to injure it by advancing stiffened components drainage, or pericatheter leakage.
beyond the parenchyma. Seldinger exchange
concludes with placement of a 0.035-in. guide-
wire into the collecting system. Over this wire, 20.4.2 Internal-External Devices:
a nephrostomy tube can be inserted; or, a sheath Nephroureteral Stents
can be placed to facilitate access to the ureter
and urinary bladder [16]. Percutaneous nephroureteral stent (NUS) is a more
If all the above procedures are unsuccess- stable urinary drainage device than a simple neph-
ful, a combined approach with urologist may rostomy. It has a ureteral limb with a pigtail in the
be most appropriate. By performing a combined bladder. The external portion of the catheter is
approach, contrast can be injected retrograde into indistinguishable from a simple nephrostomy.
the ureter of interest through a cystoscope, pro- It is important to match the length of the ure-
viding a direct fluoroscopic target of the calyces. teral limb of the catheter to the length of the
This approach also allows distension of the renal ureter. The length of the NUS depends on the
calyces if enough contrast is injected [16]. patient’s height. Patients shorter than 178 cm
typically receive a 22-cm ureteral limb. Between
heights of 178 and 193 cm, a 24-cm NUS typi-
20.4 Urinary Drainage Devices cally suffices. More than 193 cm, a 26-cm tube is
usually required [21].
Urinary drainage can be external (nephrostomy): It is important to make allowance for extra
internal-external (nephroureteral stent) or inter- length when hydroureteronephrosis causes sub-
nal (double-J stent, metallic stents) without an stantial ureteral dilation and tortuosity or if there
externalized catheter. These are the devices most is marked deviation of the ureter.
212 A.M. Ierardi et al.
Polytetrafluoroethylene has been applied as catheters may be used; alternatively, a long sheath
coating for metallic stents in animal studies and may be placed as near as possible to the obstruc-
is effective against urothelial hyperplasia [24]. tion to ensure more stability, and a microcatheter
The clinical evidence for paclitaxel- and may be tried [22]. Usually a combination of these
chlorhexidine-eluting stents is still pending [25]. maneuvers is required to cross the obstruction,
In conclusion, metallic stents or resonance and occasionally none of them are successful.
metallic stents have been introduced to maintain When even after a reasonable effort it’s impos-
prolonged patency of ureters compromised by sible to accomplish the procedure, a nephros-
encasing neoplasm ([26, 27], but they are asso- tomy catheter is placed, and the patient may be
ciated with epithelial hyperplasia and have not reschedule for a second attempt after few weeks
been helpful, even in malignant cases with short of external drainage. The rationale of a second
survival expectancy [28]. attempt is to not have inflammation associated
with organic obstruction after a period of exter-
nal drainage [3].
20.5 Stent Placement After crossing the obstruction, contrast media
is injected to visualize ureteral anatomy not seen
Following successful access to the collecting sys- by anterograde pyelography. The catheter can
tem, anterograde pyelography demonstrates the then be advanced over the wire into the urinary
location of ureteral obstruction. Maneuvers to bladder where contrast injection is performed to
cross the obstruction are facilitated and secured document the correct intravesical position. Wire
by use of a safety wire and a side-arm sheath. A passage into the urinary bladder often produces
true safety wire in this context is placed along- irritative bladder symptoms that can be minimized
side the working sheath to secure access. A safety by placing only as much wire as needed into the
wire can be obtained by placing a second wire viscus. Injection of several cc lidocaine into the
through the sheath already in place and remov- urinary bladder can also reduce symptoms of
ing and reinserting the sheath over one of the two bladder spasm related to catheter placement [3].
wires [3].
An angled catheter is then placed in the ure-
ter proximal to the point of obstruction, and a 20.5.1 Ureteroplasty and Cutting
guidewire is placed through it. Guidewires with Balloon
either straight, shapeable, or gently curved tips
to try to cross the obstruction can be used. With In case of severe ureteral stenosis, to allow a
the angled catheter 1–2 cm above the obstruc- correct insertion of the stent, a predilation of
tion, the wire’s tip can fully assume its shape in the ureter stenosis with a 4–7-mm conventional
the ureter. The wire is then gently advanced dur- angioplasty balloon catheter can be necessary
ing continuous rotation and retracted iteratively (Fig. 20.5). In exceptional cases, it can be dif-
until it engages the obstructed lumen, at which ficult to advance a 7–8-Fr JJ-catheter over a tight
point gentle rotation and advancement of the wire resistant ureter stenosis following unsuccessful
typically delivers it into the distal unobstructed high-pressure balloon dilation [29–31].
lumen. This technique of careful “twiddling” Cutting-balloon angioplasty (CBA) represents
allows for interrogation of the ureteral surfaces an alternative system of balloon angioplasty,
at the level of obstruction, and its success relies which combines the features of conventional bal-
heavily on operator responsiveness to tactile and loon angioplasty with advanced microsurgical
visual stimuli that signal engagement of the lumi- capabilities. This newly developed device has the
nal opening followed by controlled, atraumatic potential to better dilate also ischemic and fibrotic
passage through the obstruction [22]. lesions resistant to conventional ureteroplasty,
When the obstruction is difficult to cross, dif- with a very low and controlled pressure (<8 atm.),
ferent guidewires in combination with several potentially reducing the procedural risk [32].
214 A.M. Ierardi et al.
Fig. 20.5 (a)
a b
Ureteroplasty of a severe
stenosis of the distal
ureter. (b) The guidewire
has crossed the stenosis
a b c
Fig. 20.6 (a) Capture of the distal extremity of the ure- the removed stent with the distal tip in the renal pelvis.
teral stent using a gooseneck catheter through a transure- (c) Through the guidewire, a NUS stent was correctly
teral approach. (b) Guidewire was inserted in the lumen of deployed
Fluoroscopically guided retrograde removal patients with severe stenosis due to malignancy
and replacement with snare catheters may be ([33, 35] (Fig. 20.6).
used when the cystoscopic approach is unfeasible Other advantages of the retrograde approach
or fails (patients with “frozen pelvis” or bladder- include the avoidance of a general anesthesia and
neck sclerosis in whom cystoscope manipulation the possibility to perform the procedure in the
may be difficult; malignant obstructions involv- angiographic suite in outpatients. Technically,
ing the ureteral papilla; patients with ankyloses the bladder needs to be sufficiently full to allow
who are unable to assume the lithotomy position the snare to grasp the distal end of the ureter more
for cystoscope insertion; patients with bleeding- easily. Because the male urethra is longer and
prone bladder tumors because the introduction grasping and withdrawing of the stent may be
of cystoscopy instruments that are larger in more difficult, special care must be taken when
caliber than those used in fluoroscopic removal performing these maneuvers in men [33].
carries a higher risk of bleeding; patients with The use of commercial gooseneck snare cath-
a urostomy). In such cases, the advantage of eters or homemade snares consisting of a catheter
fluoroscopically guided replacement lies in the and a hydrophilic guidewire (which, albeit more
smaller caliber of the devices (6–8 F), which difficult to manipulate) was described. Forceps-
are easier to manipulate inside the bladder and type devices have seldom been used and appear
consequently involve a lower risk of bleeding in to be poorly suited to this type of procedure
neoplastic disease. In addition, fluoroscopically owing to the small caliber of the arms [35].
guided recanalization of the stent being removed In the setting of bilateral ureteral stents, after
allows maintenance of ureteral-tract patency and the first stent has been exchanged for a wire, the
the possibility to check that the distal extrem- second stent may be captured before replacing
ity of the new stent has reached the renal pel- the first to minimize the risk of stent entangle-
vis. This maneuver is fundamental, especially in ment in the bladder [3].
216 A.M. Ierardi et al.
A cause of failure to replace the stent may Other strategies to remove an occluded stent are
occur in the presence of a urinary diversion (ure- transureteral introduction of the loop snare into
teroileal conduit). This were hypothesized to be the bladder for capture of the distal pigtail that
related to intestinal secretions or recurrent urinary is then pulled up by the ureter and out the sheath
tract infections that cause the stent to adhere to or transurethral placement of a sheath and loop
the ureteral walls and prevent its withdrawal [36]. snare for retrograde retrieval of the stent through
Some shrewdness may be considered, for the urethra [3].
example, the use of stiff guidewires or micro-wires It is important to keep in mind that retrograde
to try to cross encrustation. Retrograde replace- stent retrieval by cystoscopy may be performed
ment may also prove unfeasible in the case of by urologist if all these attempts fail [39].
proximal stent migration into the renal pelvis with
distal end at ureteral level. A further advantage is
that pyelographic intraprocedural monitoring with 20.6 Follow-Up Care
intracavitary injection of contrast material can be
performed in addition to fluoroscopic control to Nephrostomy catheters and NUS were routinely
ensure more precise and safer positioning of the recommended to be changed at 3-month intervals
cranial extremity of the stent and easier negotia- and ureteral stents at 3–6-month intervals [3].
tion of possible ureteral kinks or bends [33]. Encrusted catheters can be challenging for
both patients and IR physicians alike. This usu-
ally occurs when catheters are not changed as
20.5.4 Anterograde Retrieval frequently as recommended but is also a function
of Ureteral Stents of the catheter material, hydration status, and the
chemistry of the patient’s urine [34, 41].
The technique of anterograde removal of dou- A stiff hydrophilic wire is sometimes all that
ble-
J stent has also been described, but this is needed in this situation [3].
approach requires a large percutaneous tract and
potentially traumatizes the renal parenchyma.
As such, this should be reserved for failed retro- 20.7 Particular Clinical
grade attempts [37]. Conditions: Ureteroileal
Early occlusion of cystoscopically placed ure- Anastomotic Stricture
teral stents is an indication for percutaneous renal
drainage. In stable patients, the occluded ureteral Ureteroileal anastomotic stricture and nonvascu-
stent may be removed at the same time of the lar renal transplant complications (urinary tract
anterograde drainage [38, 39]. obstruction or leakage and the development of
After percutaneous access to the collecting peritransplant fluid collections) are conditions
system is established, a side-arm sheath is placed that may present to the attention of the interven-
into the collecting system. Through the sheath, tional radiologist.
either a loop snare or forceps is used to capture the Ureteroileal anastomotic obstruction is a pos-
proximal pigtail of the stent, which is then pulled sible complication after radical cystectomy, with
out through the sheath. Once the stent is pulled urinary diversion to an ileal conduit occurring in
out of the sheath, a wire is introduced through the up to 15.5% of patients [40].
stent and advanced back down the ureter to pre- Given associated comorbid factors, many
serve access for anterograde catheter placement. patients are not suitable candidates for surgical
When efforts to capture the proximal pigtail are revision of the anastomosis; minimally invasive
unsuccessful, repositioning of the stent pigtail alternatives including nephroureteral stenting,
into a position more optimal for capture may be balloon dilation, ureteroscopic incision, and
helpful. This can be accomplished by inflating a insertion of metallic stents were applied ([40, 41].
balloon alongside the ureteral portion of the stent Placement of transileal retrograde nephroure-
and pushing down or pulling up the entire stent. teral stents is an attractive method of managing
20 Interventional Radiology for Drainage of Urine 217
postoperative ureteroileal obstruction because it leaks occur at the distal ureter, possibly as a
reduces the need for externalized flank catheters result of necrosis due to ischemia or rejection,
in patients who are already saddled with having or at the ureteroneocystostomy site, stemming
to maintain the ileal stoma, thereby increasing from problems at the time of surgery. Leaks
patient comfort. Moreover, they are associated occur less frequently in the proximal ureter or
with minimal morbidity, easy of exchange, and pelvicaliceal system secondary to distal ureteral
durability [40]. obstruction [44].
Patients with urine leaks may present with
pain, swelling, discharge from the wound, or uri-
20.8 Interventions noma [45].
in Transplanted Kidney
a b
c d
Fig. 20.7 (a) Anterograde pyelography of a transplanted crossed with a guidewire. (c) A double-J ureteral stent was
kidney revealed a stricture (white arrow) of the ureter and deployed. (d) A nephrostomy was placed
a leak (black arrow). (b) Leak and stricture were correctly
In this last case, like for the leak in native kid- Published rates for different types of complica-
neys, the ureteral stent serves to maintain the con- tions are highly dependent on patient selection and
tinuity of the ureter and the nephrostomy drain of are, in some cases, based on series comprising sev-
the urine outside to maintain the ureter “off.” eral hundred patients, which is a larger volume than
most individual practitioners are likely to treat.
Complications may be distinguished in hem-
20.9 Complications orrhagic and septic. Moreover, inadvertent bowel
or lung transgression represent other rare but pos-
All complications are recorded and classified as sible complications [46].
minor and major [46]. After a PCN, hemorrhagic complications
Major complications were defined as com- range from mild to severe hematuria with the
plications that, if untreated, might threaten the need to perform a percutaneous embolization or
patient’s life, lead to substantial morbidity and even a total nephrectomy.
disability, result in hospital admission, or sub- Mild hematuria is also common after ureteral
stantially lengthen hospital stay. stenting as a result of urothelial irritation [10].
Minor complications included situations (like Significant hematuria after ureteral stenting
pain or mild hematuria) that do not lead to con- can be caused by arterio-ureteral fistula between
sequences, requiring no more than symptomatic the ureter and the common or internal iliac arter-
therapy and include overnight admission for ies. This rare phenomenon has been reported in
observation only. the setting of pelvic malignancies treated with
20 Interventional Radiology for Drainage of Urine 219
surgery and radiation. Inadvertent bowel trans- stasis, excluding urolithiasis and neuropathic bladder.
gression is a rare complication of PCN when World J Urol 30(1):77–83
3. Thornton RH, Covey AM (2016) Urinary drainage
the colon lies in a retro-renal position. Pleural procedures in interventional radiology. Tech Vasc
complications including pneumothorax, hemo- Interv Radiol 19(3):170–181
thorax, empyema, and hydrothorax are rare. 4. Venkatesan AM, Kundu S, Sacks D et al (2010)
Inflammatory systemic complications such as Practice guidelines for adult antibiotic prophylaxis
during vascular and interventional radiology proce-
sepsis, febrile urinary tract infections, and pyelo- dures. Written by the Standards of Practice Committee
nephritis may develop as a consequence of drain- for the Society of Interventional Radiology and
age and manipulation of potentially infected, Endorsed by the Cardiovascular Interventional
obstructed urinary systems, which are further Radiological Society of Europe and Canadian
Interventional Radiology Association [corrected]. J
compounded by the immunosuppressive state of Vasc Interv Radiol 21(11):1611–1630
advanced malignancy and subsequent systemic 5. Bultitude M, Rees J (2012) Management of renal
treatments [15]. colic. BMJ 345:e5499
There was no statistically significant differ- 6. Mokhmalji H, Braun PM, Martinez Portillo FJ,
Siegsmund M, Alken P, Köhrmann KU (2001)
ence in the overall stent-related or nephrostomy- Percutaneous nephrostomy versus ureteral stents for
related complications as well as the accumulated diversion of hydronephrosis caused by stones: a prospec-
incidence of inflammatory systemic complica- tive, randomized clinical trial. J Urol 165(4):1088–1092
tions between the two groups. Similarly, no sig- 7. Dagli M, Ramchandani P (2011) Percutaneous neph-
rostomy: technical aspects and indications. Semin
nificant difference was observed in the incidence Intervent Radiol 28(4):424–437
of urinary tract infections between the two treat- 8. Chitale SV, Scott-barrett S, Ho ET, Burgess NA
ment modalities [1]. (2002) The management of ureteric obstruction
secondary to malignant pelvic disease. Clin Radiol
57(12):1118–1121
Conclusions 9. Malloy PC, Grassi CJ, Kundu S et al (2009) Consensus
A wide range of clinical situations including guidelines for periprocedural management of coagu-
preservation of renal function, treatment of lation status and hemostasis risk in percutaneous
image-guided interventions. J Vasc Interv Radiol 20(7
infection, urinary diversion, and access for
Suppl):S240–S249
urologic intervention require urinary drainage. 10. Pabon-ramos WM, Dariushnia SR, Walker TG et al
Nowadays several techniques and devices (2016) Quality improvement guidelines for percutane-
are available. External drainage (nephrostomy) ous nephrostomy. J Vasc Interv Radiol 27(3):410–414
11. Springer RM (2015) Planning and execution of
catheters or completely internalized (double-J)
access for percutaneous renal stone removal in a
stents with NUS and retrograde nephrostomy community hospital setting. Semin Intervent Radiol.
catheters in between are those most frequently 32(3):311–322
used. Routine maintenance is required for all 12. Miller NL, Matlaga BR, Lingeman JE (2007)
Techniques for fluoroscopic percutaneous renal
these devices, and most are associated with
access. J Urol 178(1):15–23
some limitation of the patient’s lifestyle. 13. Osman M, Wendt-nordahl G, Heger K, Michel MS,
On the other side, the procedures described Alken P, Knoll T (2005) Percutaneous nephrolithot-
are permitted to manage clinical and surgical omy with ultrasonography-guided renal access: expe-
rience from over 300 cases. BJU Int 96(6):875–878
situations unsolved until a few years ago.
14. Ristau BT, Averch TD, Tomaszewski JJ (2011)
From this point of view, interventional radio- Percutaneous renal access by urologist or radiolo-
logic techniques improved the quality of life gist: a review of the literature. Nephro-Urol Mon
of these patients. 3(4):252–257
15. Carrafiello G, Laganà D, Mangini M et al (2006)
Complications of percutaneous nephrostomy in the
treatment of malignant ureteral obstructions: single-
References centre review. Radiol Med 111(4):562–571
16. Ray CE, Brown AC, Smith MT, Rochon PJ (2014)
1. Hsu L, Li H, Pucheril D et al (2016) Use of percutane- Percutaneous access of nondilated renal collecting
ous nephrostomy and ureteral stenting in management systems. Semin Intervent Radiol. 31(1):98–100
of ureteral obstruction. World J Nephrol 5(2):172–181 17. Patel U, Abubacker MZ (2004) Ureteral stent place-
2. Heyns CF (2012) Urinary tract infection associated ment without postprocedural nephrostomy tube:
with conditions causing urinary tract obstruction and experience in 41 patients. Radiology 230(2):435–442
220 A.M. Ierardi et al.
Anna Maria Ierardi, Salvatore Alessio Angileri,
Enrico Maria Fumarola, Filippo Piacentino,
Natalie Lucchina, Domenico Laganà,
and Gianpaolo Carrafiello
a b
c d
Fig. 21.1 (a) Unenhanced CT axial image shows a col- to renal parenchyma. (c) The drainage was deployed
lection in the left perirenal space. (b) After administration under US guidance. (d) One week later, contrast-enhanced
of contrast media, an enhanced rim was shown, adjacent CT showed partial resolution of the collection
224 A.M. Ierardi et al.
Curative drainage, defined as complete resolu- Daily catheter care with irrigation of the catheter,
tion of infection requiring no further operative preferably every 8 h with at least 10 mL of sterile
intervention (Fig. 21.2), may be achieved in more saline, is recommended. The decision to remove
21 Interventional Radiology in the Treatment of Abscess Collections 225
a b
c d
Fig. 21.2 (a) US showed a perirenal collection (arrows); almost complete resolution of the fluid collection and the
(b, c) contrast-enhanced CT confirmed a multiloculated pigtail drainage catheter
abscess; (d) unenhanced CT scan after 15 days showing
the catheter is multifactorial and includes nor- a perirenal abscess, which account for 2–30% of
malization of temperature and white blood cell all aspirated fluid collections in the peritransplant
count as well as reduction of drainage volume to period. Classically, these patients present with
less than 10 mL/day [20]. fever alone or with perigraft pain plus tender-
ness in a period ranging from the first 2–3 days
to weeks after transplantation [6].
21.9 Fluid Collections
in the Transplanted Kidney
21.9.1 Lymphocele
Perinephric fluid collections after renal trans-
plantation are common and are associated with a Postoperative lymphoceles are caused by lym-
number of serious complications, one of these is phatic leakage from the allograft bed or from the
226 A.M. Ierardi et al.
allograft itself and are the most common perire- If an uninfected lymphocele recurs, it is usu-
nal fluid collection, usually occurring weeks to ally treated by un-roofing into the peritoneal cav-
months after transplantation [26]. ity by either open or laparoscopic technique [6].
Renal transplant patients are predisposed to
prolonged lymphatic leakage as a result of graft
rejection, the use of steroids or diuretics, or 21.9.2 Abscess
retransplantation [27].
Most lymphoceles are small and asymptom- An abscess may arise from an infected wound or
atic, and intervention is not necessary. However, from a secondarily infected lymphocele, hema-
some lymphoceles compress adjacent struc- toma, or urinoma after attempts at aspiration
tures and may cause hydronephrosis, edema, or or as a consequence of graft pyelonephritis [6]
deep venous thrombosis in the ipsilateral lower (Fig. 21.4).
extremity, and percutaneous aspiration of the Any perigraft fluid collection can become
fluid becomes indicated [28] (Fig. 21.3). infected; usually, the affected patient presents
The most effective therapy is the combination with fever or local pain. US or CT findings usu-
of indwelling catheter drainage and sclerotherapy ally are nonspecific, but air within the perirenal
with a reported success rate of 68–100% [26]. fluid collection strongly suggests a perirenal
Various sclerosing agents can be used with abscess. Also, in the clinical setting of fever and
multiple treatments required in most cases, with leukocytosis in a transplant patient, the detection
the catheter left in place for anywhere from 4 to of a perinephric fluid collection is presumptive
35 days [29]. evidence that the fluid is infected. In these situa-
a b
Fig. 21.3 (a) Axial RM T2 image showed a lymphocele. (b) US image confirmed the possibility to deploy the drain-
age. (c) Image performed during the deployment of the drainage
21 Interventional Radiology in the Treatment of Abscess Collections 227
a b c
Fig. 21.4 (a) RM image showed an infected lymphocele. formed 10 days later demonstrated almost complete reso-
(b) US confirmed RM finding. (c) The same modality was lution of the fluid collection
used as guidance to deploy the drainage. (d) RM per-
tions, ultrasound- or CT-guided needle aspiration lections. They have resulted in reduced mor-
may confirm the diagnosis and permit the plan- bidity and mortality and have helped to reduce
ning of a percutaneous drainage [30]. length of hospital stay and hospital costs. In
Prompt surgical or percutaneous drainage conclusion, three fundamental steps can be
combined with systemic antibiotics is mandatory identified: patient selection, performing the
because of the immunosuppressed state of trans- procedure, and correct management of the
plant patients. Percutaneous drainage under US patient. In all three steps, interventional radi-
or CT guidance is associated with a high rate of ologist, supported by clinicians, has the most
success and a low complication rate [28], with the important role.
modalities previously described in this chapter [28].
If the fluid is purulent, microscopic examina-
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Urinary Tract Infections in Infants
and Children 22
Marcello Napolitano and Anna Ravelli
under the age of 7 years [11]; in particular, preva- spectrum of complicated UTIs, usually when
lence is about 5% in the subset of 2- to 24-month- collecting systems are dilated or obstructed [4].
old children according to AAP guidelines [2]. In
young children from 0 to 6 months of age, UTIs
are more diffuse among males and after 6 months 22.3 C
linical and Laboratory
among girls [11]. The exact incidence of compli- Features
cated UTIs in children is not well established yet,
but from some studies, it seems to be about 4% Clinical and biochemical findings are not spe-
in children hospitalized for suspected acute focal cific of a urinary tract infection, being com-
bacterial nephritis, renal abscess, and/or pyone- mon to other febrile infections not involving the
phrosis [4, 12–14]; in Taiwan the rate of ALN bladder and/or kidneys [9, 21]. Children with
among children with febrile UTI results higher, UTI can be very asymptomatic, having only
about 8–10% [10, 15]. The microorganisms bacteriuria, or may manifest bladder symptoms
involved in the majority of UTIs are bacteria, and/or fever [3, 11]. The most common signs
first Escherichia Coli, followed by Proteus and and symptoms of UTIs for infants younger than
Pseudomonas sp. [4, 14, 16, 17]. When infection 3 months seem to be fever, vomiting, irritability,
is due to non-E. Coli organism, it is considered an and lethargy and for older children also dysuria
atypical UTI [3]. [3]; diarrhea, poor feeding, and dehydration
Currently, some predisposing factors for UTIs have also been described in young infants
have been identified: first, congenital malforma- [14]. According to AAP, there is fever if tem-
tions (megaureter, urethral valves, renal hypopla- perature is at least 38.0 °C [2]. Children with
sia), vesicoureteral reflux (VUR), family history complicated UTIs generally present nonspecific
of renal disease, dysfunctional elimination syn- symptoms similar to those of noncomplicated
drome (DES), poor urine flow, previous UTI, infections but more severe, with septic tempera-
recurrent fever of uncertain origin, constipation, ture, and rapid worsening of clinical condition
enlarged bladder, spinal lesion, abdominal mass, [9, 14]; the differential diagnosis among differ-
poor growth, high blood pressure, and for boys ent forms of febrile UTIs based only on clinical
uncircumcision [2, 3, 11, 14]. data is not simple [5].
The role of VUR is still controversial because Furthermore, urinary tract is commonly subdi-
in the past it was thought to be the main cause vided in upper and lower tract; usually, fever and
of UTI and renal damage, but now the associa- bacteriuria in the presence or absence of lower
tion between VUR, reported in one-third of chil- back pain are considered linked to APN or upper
dren with febrile UTIs, and renal injury does not urinary tract infection, while cystitis or lower
appear so straightforward [6, 18–20]. Moreover, urinary tract infection should be considered in
the pathogenesis of renal scar remains uncertain, the case of isolated bacteriuria, with no associ-
even if VUR, delayed therapy, young age, and ated signs and symptoms. All other infants and
extension of renal injury seem to be risk factors children who have bacteriuria but no systemic
[18]. The pathogenesis of AFBN is unclear; it is symptoms or signs should be considered to have
likely due to hematic or ascending infection from cystitis/lower urinary tract infection [3].
the lower urinary tract. At histological exami- Urine collection is recommended in any case
nation, acute focal bacterial nephritis shows of febrile infant suspected to have an infectious
hyperemia, interstitial edema, and leukocyte involvement of urinary tract [2, 3]. The specimen
infiltration [14, 16]; area of acute pyelonephritis for the culture of the pathogen and urinalysis,
presents similar features but milder, while intra- intended as the research of bacteria and leuko-
parenchymal abscess is a focal, purulent paren- cytes at microscope and leukocyte esterase and
chymal cavity with peripheral wall and internal nitrite tests, has to be collected through the ure-
liquefaction and necrosis [5]. Pyonephrosis is thral catheterization or suprapubic aspiration to
another inflammatory condition included in the avoid any contamination. Positive microscopy,
22 Urinary Tract Infections in Infants and Children 233
a b c
d e
Fig. 22.1 A 5-month-old boy affected with megaureter dilated (arrow) with declivous hyperechoic debris (aster-
and pyonephrosis. (a) US transverse image showing dila- isk), B = bladder; (d) US transverse image showing
tation of pelvis and calyces of the right kidney with pres- hydronephrosis of the right kidney with concomitant thin-
ence of debris (asterisk) in the calyces (arrow); (b) US ning of the renal parenchyma and decreased vasculariza-
transverse image showing dilatation of the distal tract of tion at color Doppler interrogation (arrowhead); (e) US
the right ureter (arrows) with hyperechoic debris in the longitudinal image with color Doppler analysis showing
dependent position (asterisk), B = bladder; (c) US longitu- normal perfusion of the left kidney without signs of
dinal image showing the distal tract of the right ureter hydronephrosis
234 M. Napolitano and A. Ravelli
Several authors reported a poor accuracy of 2 days of treatment. If the patient shows sig-
US in detecting urinary tract abnormality, with nificant improvement of clinical situation, early
sensitivity ranging from 12 to 79% and specific- US examination during the acute infection is not
ity from 41 to 99%, [2, 19, 22–30], with a spe- mandatory.
cific sensitivity for detecting VUR (evidence of
urinary tract dilatation) of 10% and a positive
predictive value of 40% [19]. According to recent 22.4.2 Voiding Cystourethrography
guidelines from the American Academy of Pedi-
atrics, 1–2% of US abnormalities lead to further The goal of voiding cystourethrography (VCUG)
investigations or surgery, while the rate of false is to identify genitourinary abnormalities which
positive is about 2–3%. However, for its advan- may favor urinary tract infection and lead to renal
tages, US is commonly well accepted by parents, damage. Vesicoureteral reflux has been for long
and benefits-harm balance is considered in favor time the primary focus of imaging, because it
of performing US in case of suspected acute was believed to be strongly associated with renal
febrile UTI [2]. lesion. In healthy pediatric population, VUR
According to NICE guidelines, it is possible prevalence has been estimated to range between
to divide UTIs in three different categories: typi- 0.4 and 1.8%, while it is present in about one-
cal, atypical, and recurrent. Atypical UTI com- third of children, who experienced febrile UTI
prises non-E. Coli infections, presence of bladder [31, 32]. The real role of VUR, especially of
or abdominal mass, high value of creatinine, sep- high grade, in the development of APN, has
sis, nonresponse to antibiotics within 48 h, and not been clarified yet [2, 3, 11, 30, 33]. Asso-
poor urine flow. Recurrent UTI can be defined as ciation of VUR with UTI seems to have higher
more than one episode of acute upper or lower risk of renal damage, but it is also reported that
urinary tract infection [3]. NICE guidelines give pyelonephritis can develop in infants and chil-
different recommendation regarding the use of dren without any demonstrable VUR as well
ultrasound in case of febrile UTI either based on [31]. Currently, it does not exist any laboratory
the type or on the age of the patient. Three differ- or clinical test to discover in advance infants
ent groups can be identified: (1) 0–6 months, (2) and children with VUR, so VCUG remains the
6–36 months, and (3) >36 months. gold standard to detect and grade it. Moreover,
Ultrasound is recommended during the acute this test allows to detect bladder dysfunction and
infection in the presence of atypical or recurrent also urethral abnormalities. It is clear that VCUG
UTI for infants younger than 6 months, while is an invasive procedure, uncomfortable for the
for infants who has positive response to treat- little patients and not well accepted by their par-
ment within 48 h, US is recommended within 6 ents because of catheterization and use of ion-
weeks from the acute episode. Ultrasound during izing radiation, so it should not be performed
the acute infection is recommended only in the routinely. Regarding the average radiation dose
presence of atypical UTI for patients with more derived from VCUG, it is not easy to estimate,
than 6 months, while patients with recurrent UTI because it depends on the fluoroscopy time and
are recommended to undergo US within 6 weeks on the use of conventional or pulsed digital fluo-
from the acute episode. Moreover, children who roscopy. NICE and AAP give some indication
have positive response to antibiotics within 48 h about performing VCUG; NICE guidelines sug-
should not undergo any imaging investigation. gest to perform VCUG in infants younger than
Current practice guidelines of the American 6 months just in case of atypical or recurrent UTI,
Academy of Pediatrics refer to infants and young while in children aged 6–36 months, VCUG is
children 2–24 months of age, recommending recommended only in the presence of hydrone-
to perform US to detect complications if clini- phrosis on US, poor urine flow, and family his-
cal situation is severe or there is no improve- tory of vesicoureteral reflux and when E. Coli is
ment of the clinical condition during the first not the pathogen responsible [3]. AAP is of the
22 Urinary Tract Infections in Infants and Children 235
same opinion, suggesting not to perform VCUG after the injection before undergoing the scan;
always after the first episode of fever due to UTI, and finally the spatial resolution is poor [40, 42].
but just in case of complex clinical situation, US Current practice guidelines of the UK National
dilatation, renal scarring, suspected obstructive Institute for Clinical Excellence recommend to
uropathy, or high-grade VUR, usually, the com- perform DMSA 4–6 months after the acute infec-
mittee recommends to perform VCUG after the tion in infants younger than 36 months in case
second episode of febrile UTI. of atypical or recurrent UTI and only in case of
recurrent UTI for children 36 months old or older.
Technetium (Tc)-99m DMSA is considered the The use of magnetic resonance imaging in
gold standard for detection and quantification pediatric radiology is increasingly widespread,
of acute pyelonephritis and for identification of because it provides noninvasive evaluation,
renal scarring in children [9, 34–36]; its sensi- anatomical and functional information, high
tivity for renal cortical abnormalities has been accuracy, and soft tissue contrast, without radia-
reported to be higher than that of US or intrave- tion exposure [4, 40–42]. In literature there are
nous urography, ranging between 80 and 100% some studies which compare MRI with the gold
[37–39], while its sensitivity is still in discussion standard DMSA for the identification of renal
with respect to MRI [40–42]. Renal scar is one parenchymal defects in infants and children
of the possible sequelae after a febrile UTI; gen- with febrile UTIs; different protocols were used,
erally, on DMSA it appears as photopenic area, with or without dynamic contrast-enhancement
due to focal ischemia and tubular dysfunction; technique, known as MR urography (MRU),
it may appear as retraction of renal parenchyma which enables to study renal morphology and
with calices deformity. The affected kidney may perfusion together with anatomical and func-
become small and irregular in shape, in case tional status of the collecting system [40–42,
of multifocal scars. Detection of scarring has a 47]. Kavanagh et al. [42] reported a sensitivity
prognostic value, because it can lead to recurrent of 77% and a specificity of 87% for detection
pyelonephritis in adulthood, renal hypertension, of renal scarring and sensitivity of 75% and
and renal insufficiency [40, 43, 44]. Although specificity of 98% for detection of focal paren-
DMSA is very sensitive to detect focal renal chymal abnormality using a coronal fat-satu-
defect, it does not allow to discriminate different rated T1-W sequence. The authors of the study
underlying conditions [9, 18, 41]; in fact, acute reviewed the discordant DMSA/MRI cases and
pyelonephritis, permanent scar, cortical cysts, concluded that MRI seemed to be the more pre-
renal abscesses, hydronephrosis, and calculi cise examination. Cerwinka et al. [40] reached
appear in the similar way as focal tracer uptake a similar conclusion, even if in their study they
defects [9, 41]. Then, it would be preferable to used also T1-weighted post-contrast sequences.
perform it no earlier than 6 months from the Kovanlikaya et al. [41] reported the sensitivity
acute episode of febrile UTI so that acute tem- and the specificity of MRI in the detection of
porary lesions have the time to heal [45]. This pyelonephritic lesions as about 91 and 89%,
nuclear medicine technique has different disad- respectively. Vivier et al. [47] concluded that
vantages to take in consideration: first of all it is DWI sequences as well allow to detect a sim-
not radiation-free, even if the radiation dose is ilar number of renal lesions with a sensitivity
generally low (about 1 mSv) [46]; secondarily, it of 100% and specificity of 93.5%, compared to
requires positioning of a cannula for intravenous T1-weighted post-contrast images.
administration of the radiotracer; it takes a long MRI is superior to DMSA in terms of con-
time because patients have to wait some hours trast and spatial resolution; it can differentiate
236 M. Napolitano and A. Ravelli
between acute pyelonephritis and renal scar, but In our institution, the use of MRI in case of sus-
it also allows to discriminate parenchymal defect pected urinary tract infection is accepted in case
among other renal lesions such as small corti- of complicated UTI, for instance when US reveals
cal renal cyst, well identifiable on T2-weighted renal lesion suspected for abscess, pyelonephritis,
images, or nephrolithiasis [40, 41]. Moreover, or acute focal lobar nephritis; in such cases, we use
MRI has the possibility to show the kidneys in a standard protocol, which consists of pre-contrast
multiple planes. Some authors have demonstrated T2-weighted, DWI, and T1-weighted sequences
that on post-gadolinium inversion recovery, MR followed by dynamic study with late urographic
images of acute pyelonephritis had hyperintense images, providing morphological evaluation of
signal, while renal scar was seen as cortical thin- the collecting system; injection of furosemide
ning, parenchymal defect, or irregular contour just before dynamic acquisition is routinely per-
without any signal change [39, 41]. However, formed. In our experience, MRI allows to identify
MRI has some disadvantages such as the risks and discriminate renal lesions and detect eventual
derived from sedation, necessary for infants and underlying urinary tract anomalies, guiding the
often for some young child, the limited accessi- choice of subsequent management (Figs. 22.2,
bility and the elevated costs [40]. 22.3, 22.4, 22.5, and 22.6).
a b c
d e
g h
Fig. 22.2 A 16-year-old girl affected with acute pyelone- (arrow); (d) axial DWI b800 image showing striated
phritis was admitted to hospital due to right lumbar pain, appearance of renal parenchyma with areas of restricted
fever, and rise of white blood cell count. (a) Axial signal (arrow); (e) ADC map confirming the parenchymal
T1-weighted fat-suppressed MR image showing an alterations seen in DWI image (arrow); (f) coronal
enlarged right kidney with reduced corticomedullary dif- T1-weighted fat-suppressed post-contrast image showing
ferentiation; (b) axial T1-weighted fat-suppressed post- multiple wedge-shaped cortical hypovascular lesions in
contrast image showing multiple wedge-shaped cortical the right kidney (arrow). Ultrasonography ((g) longitudi-
hypovascular lesions in the right kidney (arrow) as for nal view, (h) transverse view) shows an enlarged right
acute pyelonephritis; (c) coronal T1-weighted fat- kidney with hyperechoic upper pole. There is no evidence
suppressed image showing enlargement of the right kid- of intraparenchymal abscess or mass
ney with some hypointense focal area in the cortex
22 Urinary Tract Infections in Infants and Children 237
a d f
c e
Fig. 22.3 A 6-year-old girl with history of recurrent characterized by hypersignal (arrow); (d) coronal
pyelonephritis of the right kidney. (a) Axial T2-weighted T2-weighted image showing the right kidney smaller than
image showing the right kidney smaller than left with an left with loss of corticomedullary differentiation; (e) coro-
area of loss of corticomedullary differentiation; (b) axial nal DWIBS image showing hypersignal parenchyma as
T1-weighted fat-saturated post-contrast image showing for pyelonephritis (arrow); (f) fluoroscopy image showing
hypoperfused-affected renal parenchyma (arrow); (c) vesicoureteral reflux of III grade
axial DWI b = 800 image showing the pyelonephritic area
a b c
e f g h
Fig. 22.4 A young boy with abscess in the left kidney. in arterial (e), parenchymal (f), and excretory phase (g)
(a) Axial T2-weighted image showing round-shape intra- showing the absence of vascularization inside the abscess
parenchymal abscess with hypersignal core (asterisk) and and initial excretion of contrasted urine in left pelvis
hypointense border; (b) coronal T2-weighted image (arrow); (h) axial T1-weighted fat-suppressed image
showing the abscess (asterisk) in the superior portion of showing the hypointense core of the abscess; (i) axial
the left kidney. Axial DWI b800 image (c) and ADC map T1-weighted fat-suppressed post-contrast image showing
(d) showing restriction of the signal of the abscess core. normal vascularization of the renal parenchyma around
Coronal T1-weighted fat-suppressed post-contrast images the abscess (arrow)
22.4.7 Voiding Urosonography of the walls of the upper urinary tract (pelvis
and proximal ureter), hyperechogenicity of the
Contrast-enhanced voiding urosonography renal sinus, and areas of altered parenchymal
(VUS) has emerged in the last years as alternative echogenicity [57]. Sensitivity of US in detect-
imaging modality to assess VUR with a reported ing APN is not very high (about 50–60%), and
sensitivity and specificity of about 100% (95% the examination can be totally normal, even in
CI 96.5–100%) compared with the gold standard the presence of acute inflammation. Color and
VCUG [54, 55]. Moreover, Duran et al. demon- power Doppler analysis can increase sensitivity
strated that VUS is a reliable technique also for of conventional US until 80–85% compared to
evaluation of the neck of the bladder and the ure- CT, depicting APN as hypovascular regions [58].
thra in children [56]. On contrast-enhanced CT scan, APN is charac-
terized by striated appearance with hypovascular
wedge-shaped areas of varying extension, paren-
22.5 C
omplicated UTIs: Imaging chymal swelling, and reduction of corticomedul-
Findings lary differentiation [58, 59]. APN has similar
appearance on gadolinium-enhanced MRI: on
22.5.1 Acute Pyelonephritis (APN) T1-weighted images, it has low signal, while on
inversion recovery images, it has increased signal
Typical US signs in case of APN include focal intensity compared to normal renal parenchyma
or diffuse increase of renal volume, reduction [39, 41], while on diffusion-weighted images,
of corticomedullary differentiation, thickening APN appears bright [47].
22 Urinary Tract Infections in Infants and Children 239
a c f
Fig. 22.5 A 5-year-old girl affected with complicated suppressed post-contrast images showing not enhanced
acute lobar nephronia. (a) Coronal DWI b800 image foci of abscess (arrow); (e) US longitudinal image show-
showing several hyperintense small foci of abscess located ing round-shape focal mass with inhomogeneous struc-
in the superior portion of the right kidney (arrow). (b) ture due to presence of fluid content (arrows); (f)
ADC map confirming multiple microabscesses with cystourethrography showing vesicoureteral reflux of
restricted signal in the superior portion of the right kidney grade III (arrows)
(arrow). Coronal (c) and axial (d) T1-weighted fat-
22.5.2 Acute Focal Bacterial not show any abnormality of the infected regions,
Nephritis (AFBN) becoming evident in post-contrast images as ill-
defined, wedge-shaped hypoperfused areas of
At ultrasonography, AFBN usually appears as renal parenchyma [16, 62].
circular, hypovascular lesion in the renal paren-
chyma, with ill-defined irregular margins and
loss of corticomedullary differentiation. It can 22.5.3 Renal Abscess
be hypo-, hyper- or isoechoic depending on the
phase of the infection; in the early stage, it is On US, typical signs of renal abscess consist
more echoic and becomes hypoechoic later [9, of hypoechoic, usually round-shape area, with
16, 60]. Among the imaging findings of AFBN, thick wall. Contrast-enhanced CT scan and
severe nephromegaly reflecting acute renal post-contrast MR images typically show renal
inflammation, and defined as renal length of abscess as a rounded, well-defined lesion with
greater than mean + 3 SD for age, demonstrated avascular core and hypervascular, irregular
a diagnostic sensitivity of 90%, rising to 95% if peripheral walls, with restricted diffusion signal
associated with a focal renal mass, with specific- in DWI sequences and relative ADC map. Pres-
ity of about 86%, compared to the gold standard ence of intralesional air is suspected for abscess
CT [61]. Non-enhanced CT images usually do formation [63]. CT and MR scan allow precise
240 M. Napolitano and A. Ravelli
a c e
b d
Fig. 22.6 A 3-year-old boy with complicated pyelone- shape areas of pyelonephritis (arrowheads) in the upper
phritis was admitted to hospital due to fever and vomit. He pole of the right kidney; (d) sagittal T2-weighted fat-
was treated with antibiotic therapy for pyelonephritis saturated image shows altered parenchymal signal in the
1 month before, and parents referred recent mild abdomi- lower pole of the right kidney (arrowhead) near the perire-
nal trauma. At physical examination, he had positive right nal collection; (e) coronal T1-weighted post-contrast
renal percussion. Axial T1-weighted pre-contrast (a) and image shows a hypovascular triangular-shape area of
post-contrast (b) MR images show a subcapsular hematic pyelonephritis in the upper pole of the right kidney
collection at the lower pole of the right kidney (arrow); (c) (arrowhead) and the subcapsular hematic collection at the
axial T1-weighted post-contrast image well depicts a lower pole (arrow)
small intraparenchymal abscess (arrow) and triangular-
evaluation of extrarenal extension of the purulent collecting system with debris localized below
collection [64, 65]. (Fig. 22.4). the iodate urine and is useful to exclude associ-
ated parenchymal lesion and tumoral cause of
obstruction, while in case of radiopaque calculi,
22.5.4 Pyonephrosis non-enhanced CT can easily identify them [64].
a b
c d
Fig. 22.7 A 2-year-old girl with left-sided infected ure- US images in transverse and longitudinal view showing
terohydronephrosis of the upper pole collecting system in debris within the dilated ureter (arrows) in proximity of
a patient with bilateral duplex collecting system. (a, b) the bladder (B); (d) US longitudinal images of the right
Longitudinal US images showing dilatation of the supe- and left kidneys showing pyonephrosis of the dilated left
rior district with hyperechoic debris without any internal upper pole collecting system (arrow)
vascularization (arrows) consistent with pyonephrosis; (c)
a b
Fig. 22.8 A 7-year-old girl affected with cystitis. (a) US transverse image showing diffuse thickened bladder wall
(arrows); (b) US longitudinal image showing increased vascularization of bladder wall (arrowheads)
242 M. Napolitano and A. Ravelli
22.7.1 Treatment
22.6.2 Fungal Infections
Treatment of UTI is based on administration of
Fungal infections are rare in healthy children. antibiotic therapy. Early treatment, in absence
The most affected are premature babies, and the of antibiogram response, is usually empiric and
most common responsible pathogen is Candida should be based on broad spectrum antibiotics.
albicans. It is believed that pathogens reach kid- According to several authors, there is no sig-
neys primary by hematogenous diffusion [78]. nificant difference in efficacy between oral and
US examination may show an enlarged kid- parenteral antibiotics [2, 84, 85]. The total dura-
ney with hyperechoic cortex, which has to be tion of antibiotic therapy changes on the basis of
22 Urinary Tract Infections in Infants and Children 243
a b
Fig. 22.9 A 1-year-old boy with infected urachus remnant. US transverse image showing hypoechoic markedly thick-
ened urachus walls (a) with increased vascularization on color Doppler analysis (b)
the diagnosed renal lesion. Even if the optimal reflux is still controversial. Several studies, con-
duration of antimicrobial treatment has not been ducted in the last decade, have suggested that
determined yet, AAP recommends antibiotics for prophylaxis does not manage to prevent recur-
at least 7 days to treat UTI [2]. In case of AFBN, rent febrile UTI as desired [90–94]; on the other
antibiotic therapy should be continued for at least hand, the most recent “Randomized Interven-
2–3 weeks, with intravenous administration at tion for Children With Vesicoureteral Reflux
least until 2–3 days after defervescence [9, 16, study” reported that the risk of recurrence of
17]; however, it seems that the duration of ther- febrile UTI was lower (about 50% less) in the
apy does not reduce the risk for renal scarring group of children who received prophylaxis
[18, 84]. Instead, in presence of renal abscess, with respect to the children who had placebo
the minimal duration of treatment should be [95]. Brandstrom as well reported a reduction of
4 weeks, also when abscess requires surgical the infection rate in children who received anti-
intervention (drainage) [49, 86]. Early drainage biotic prophylaxis [11].
is recommended also in case of suspected pyo-
nephrosis as diagnostic and therapeutic tool [59,
87]. Early diagnosis of first-time or recurrent UTI 22.7.3 Follow-Up
is relevant to promptly start the proper antibiotic
therapy, in order to limit renal damage and risk Infants and children who become asymptom-
of renal scarring [18, 88]. Instead, the value of atic after the first episode of febrile UTI should
treatment of the reflux, either medical or surgi- not routinely undergo urinalysis but should be
cal, is still controversial, because the role of VUR retested only in occasion of recurrent infections,
in the pathogenesis of febrile UTI and renal scar in order to proceed as soon as possible with the
remains unclear [2, 19, 84, 89]. most effective antibiotic therapy [2, 3].
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