Renal Relevant Radiology: Radiologic Imaging in

Autosomal Dominant Polycystic Kidney Disease

Frederic Rahbari-Oskoui,* Ankush Mittal,* Pardeep Mittal,† and Arlene Chapman*

Summary
Autosomal-dominant polycystic kidney disease is a systemic disorder and the most common hereditary renal
disease, which is characterized by cyst growth, progressive renal enlargement, and development of renal failure.
The cystic nature of autosomal dominant polycystic kidney disease and its renal and extrarenal complications Departments of
*Medicine and
(kidney stones, cyst hemorrhage, intracerebral aneurysm, liver cysts, cardiac valve abnormalities, etc.) give †
Radiology, Emory
radiologic imaging studies a central role in the management of these patients. This article reviews the indications, University School of
comparative use, and limitation of various imaging modalities (ultrasonography, magnetic resonance imaging, Medicine, Atlanta,
computerized tomography scan, Positron emission tomography scan, and renal scintigraphy) for the diagnosis and Georgia
management of complications in autosomal dominant polycystic kidney disease. Finally, this work provides ev-
idence for the value of total kidney volume to predict disease progression in autosomal dominant polycystic kidney Correspondence:
Dr. Arlene Chapman,
disease. Emory University
Clin J Am Soc Nephrol 9: 406–415, 2014. doi: 10.2215/CJN.08940813 School of Medicine,
1364 Clifton Road
Suite GG23, Atlanta,
GA 30322. Email:
Introduction cysts with associated renal enlargement (Figure 1A) abchapm@emory.org
Autosomal-dominant polycystic kidney disease (1). The number and distribution of renal cysts, kidney
(ADPKD) is the most common hereditary kidney size, and presence of associated features, including liver
disease and a systemic disorder, which is character- cysts (5), differentiate ADPKD from other hereditary
ized by progressive kidney cyst growth and enlarge- cystic disorders (6).
ment, leading to decline in kidney function and ESRD Three decades ago, Ravine et al. (7) established the
(1). There are two identified genes, polycystic kidney original diagnostic criteria for ADPKD based on US
disease 1 (PKD1) and PKD2, that code for polycystin imaging. The absence of cysts by the age of 30 years
1 and 2, respectively. Mutations in PKD1 and PKD2 in at-risk individuals indicated a less than 5% likeli-
genes account for approximately 85% and 15% of cases, hood of inheriting the disease. However, given the later
respectively. PKD2 disease has a less severe phenotype development of cysts in patients with PKD2 disease, a
and a later age of onset of ESRD than PKD1 disease high false-negative rate was found in PKD2 family
(mean age574.0 versus 54.3 years) (2). Renal and extra- members. An international consortium of PKD experts
renal manifestations can be life threatening in ADPKD. recently established a unified US criteria for diagnosis
Diagnosis and management of ADPKD and its compli- for all ADPKD patients (8,9) (Table1). The following
cations require specific imaging techniques and multi- criteria are recommendations for a diagnosis by US in
disciplinary teamwork including nephrologists and at-risk individuals for ADPKD:
radiologists. In this article, we review the different im-
aging modalities and their indications in patients with (1) Individuals 15–39 years of age: at least three kidney
ADPKD. cysts (unilateral or bilateral).
(2) Individuals 40–59 years of age: at least two cysts in
Diagnosing and Screening for ADPKD each kidney.
Ultrasonography (US), the current imaging modal- (3) Individuals older than 60 years of age: at least four
ity of choice for diagnosing ADPKD, was developed cysts in each kidney.
during World War II, and clinical use began in the
early 1960s. The grayscale technology and acoustic As a consequence, an US with zero or one cyst at age
contrast between normal renal parenchyma (slightly 40 years excludes ADPKD with certainty in at-risk
hypoechoic/isoechoic to liver) and renal cysts (anechoic subjects. US in at-risk children is less helpful in ruling
round structures with a prominent posterior enhance- out disease, especially before the age of 5 years, when
ment) make this modality preferable. The availability, 50% of imaging studies are inconclusive (10). How-
portability, low cost, noninvasiveness, and lack of radi- ever, the presence of one cyst is adequate for the di-
ation have established US as the most widely used agnosis in at-risk children (0–15 years of age). In
imaging tool to diagnose ADPKD (3). US is accurate infants, the presence of large echogenic kidneys with-
and detects cysts larger than 0.5 cm in diameter (4). out distinct macroscopic cysts is highly suggestive of
Typical ADPKD kidneys have multiple bilateral renal ADPKD.

406 Copyright © 2014 by the American Society of Nephrology www.cjasn.org Vol 9 February, 2014
Clin J Am Soc Nephrol 9: 406–415, February, 2014 Imaging Studies in ADPKD, Rahbari-Oskoui et al. 407

Figure 1. | Ultrasonography and magnetic resonance imaging (MRI) imaging of patients with autosomal dominant polycystic kidney disease
(ADPKD) compared with bilateral simple acquired cysts. (A) Longitudinal ultrasonographic view of the right kidney showing multiple dark
hypoechoic lesions throughout the kidney with kidney enlargement, consistent with ADPKD. (B) Coronal T2-weighted MRI images show
multiple tiny T2 high signal lesions in both kidneys with well preserved renal parenchyma in a patient with bilateral acquired cysts (arrows). (C)
Coronal T2-weighted and (D) coronal unenhanced three-dimensional T1-weighted gradient echo MRIs of a patient with ADPKD and con-
served renal function show multiple cystic lesions. Lesions with high T2 signal and low T1 signal represent simple cysts (arrow), whereas
hemorrhagic cysts show low T2 signal and high T1 signal (star). Preserved renal parenchyma is seen between the cysts (double arrow).

Renal enlargement is a universal and unique character-
istic of ADPKD, and as seen below, it is a key feature for
risk for progression to renal failure. However, increase in
renal size has not yet been included in the diagnostic
criteria for ADPKD. A challenging question is to define renal
enlargement based on US measurements. Renal length varies
based on age, height, and sex (related to height) (11). Also,
population-based US studies of completely normal individ-
uals without kidney problems or risk factors for CKD are
sparse. Because of these difficulties, normograms for renal
size have not been developed in healthy adults. Further-
more, the existing renal length normograms in the pediatric
population based on age have limited use in ADPKD, be-
cause renal enlargement in affected individuals is often miss-
ing in that age group. The closest estimation of kidney size
based on body height comes from a study of 202 consecutive
patients who had US for nonrenal abdominal pain (Figure 2)
(12), but information on kidney function and risk factors for
CKD (hypertension, diabetes, proteinuria, hematuria, etc.)
was unavailable in those patients. The commonly encoun-
tered case of an older patient (.60 years of age) with more
than four cysts on each kidney and impaired kidney func-
tion evoking either ADPKD or acquired cystic kidney dis-
ease is relatively easy to differentiate. Patients with ADPKD
present with frank renomegaly (.1084 ml or fivefold the
normal size) by the time that CKD stage 3 has developed
and innumerable cysts, whereas patients with acquired cys-
tic kidney disease will have a limited number of cysts in
kidneys that are reduced or of normal size that are echogenic
with a thin cortex. In less typical cases (absence of family
history of ADPKD, borderline number of cysts, and absence
of frank kidney enlargement), serial imaging studies to doc-
ument cyst growth or genetic testing may be necessary to
confirm a diagnosis of ADPKD. The percentage of individ-
uals with ADPKD who meet these latter criteria is currently
less than 3% of affected individuals (Consortium of Radio-
logic Imaging Study of PKD [CRISP] data).
Computerized Tomography and Magnetic Resonance
Imaging
Computerized tomography (CT) and magnetic resonance
imaging (MRI) can detect cysts,1 cm in diameter and often
down to 1 mm (4,13). Therefore, screening potential kidney
donors or at-risk individuals by CT or MRI often leads to the
detection of simple renal cysts not related to ADPKD. In the
absence of established and widely accepted diagnostic crite-
ria for ADPKD using MRI or CT, clinicians must rely on the
classic phenotype of ADPKD, which includes enlarged kid-
neys and presence of liver cysts, or rely on genetic testing to
rule out ADPKD.
CT
There are no validated diagnostic CT criteria for ADPKD.
However, CT has been used effectively in affected indi-
viduals with very mild disease when no cysts are detect-
able by US (,5% of cases). Incidental discovery of renal
cysts and PKD is most often made during the workup for
408 Clinical Journal of the American Society of Nephrology

Unit50–20), with an imperceptible wall and no enhance-

Table 1. Ultrasound criteria for diagnosis and exclusion of ment after administration of contrast agents. Complex renal
autosomal dominant polycystic kidney disease cysts are irregular in shape and have thicker or calcified walls
and hyperdense content (usually serosanguinous or mu-
Unknown
PKD1 PKD2 ADPKD coid material) with Hounsfield Unit.20 (14).
Gene Type False-positive diagnoses of ADPKD occur with CT because
of the high prevalence of simple cysts in the general population
Diagnosis (24%–47%) (15). The reported prevalence rates of simple cysts
15–29 yr increase with age and in men (9%, 27%, 48%, and 60% of
$3 cystsa individuals,40, 40–60, 60–80, and .80 years of age, respec-
PPV: 100% PPV: 100% PPV: 100% tively) (15–17). Bilateral simple cysts occur in 18%, 30%, and
Sens: 94.3% Sens: 69.5% Sens: 81.7%
45% of individuals,60, between 60 and 80, and .80 years of
30–39 yr
$3 cystsa age (17). CT remains useful for diagnosing ADPKD when
PPV: 100% PPV: 100% PPV: 100% cysts larger than 1 cm only are considered. The frequency of
Sens: 96.6% Sens: 94.9% Sens: 95.5% simple cysts.1 cm in diameter is markedly reduced, and the
40–59 yr current diagnostic criteria for ADPKD remain intact.
$2 cysts
(in each
MRI
kidney)
MRI is as accurate as CT to visualize renal cysts as small as
PPV: 100% PPV: 100% PPV: 100%
Sens: 92.6% Sens: 88.8% Sens: 90% 1 mm (4), and it is helpful in the evaluation of complex cysts
Exclusion (18). A simple cyst is uniformly hyperintense on T2-
15–29 yr weighted images and shows no enhancement after contrast
$1 cysta medium injection (Figure 1B). Complex renal cysts may be
NPV: 99.1% NPV: 83.5% NPV 90.8% irregular in shape, have thick or calcified walls, and have a
Spec: 97.6% Spec: 96.6% Spec: 97.1% complex signal intensity (bright T1 and dark T2 or bright T1
30–39 yr and T2 images) (Figure 1C) (18).
$1 cysta Comparative data on performance characteristics of
NPV: 100% NPV: 96.8% NPV 98.3% US versus MRI for diagnostic accuracy in ADPKD are un-
Spec: 96% Spec: 93.8% Spec: 94.8%
available. However, similar to CT, current diagnostic criteria
40–59 yr
$1 cysta for ADPKD are applicable to MRI if cysts larger than 1 cm are
NPV: 100% NPV: 100% NPV 100% included (13). A prospective cohort of 115 at-risk patients
Spec: 93.9% Spec: 93.7% Spec: 93.9% formally compared the two modalities, indicating a higher
sensitivity for MRI (98% versus 95%) and equal specificity
All values presented are mean estimates. PKD1, polycystic (98%) based on the presence of five or more bilateral cysts
kidney disease 1; PKD2, polycystic kidney disease 2; ADPKD, on MRI compared with only three or more bilateral cysts
autosomal-dominant polycystic kidney disease; PPV, positive on US when diagnosing ADPKD (oral presentation by York
predictive value; Sens, sensitivity; NPV, negative predictive Pei at the Renal Week of the American Society of Nephrology,
value; Spec, specificity. Adopted from reference 55, with per- October 30–November 4, 2012, in San Diego, CA).
mission. Recommendations regarding the use of imaging studies
a
Unilateral or bilateral. for screening and diagnosis of ADPKD are listed:

(1) US is the modality of choice.

(2) Renal enlargement is a key feature of ADPKD but not in-
corporated into the diagnostic criteria.
(3) CT and MRI will detect simple cysts with high frequency,
but if cyst size is limited to $1 cm, they can be used to
screen for ADPKD with better resolution that US.
(4) Unified age-specific US diagnostic criteria for ADPKD
based on cyst number are now available.

Imaging Studies for Complications of ADPKD

Figure 2. | Correlation between kidney length and body height in
adults. Solid line, ANOVA; dotted line, 95% confidence limits. Re-
printed from reference 12, with permission.
abdominal pain. CT is particularly useful in evaluating the
renal complications of ADPKD, including kidney stones,
cyst hemorrhage, infection, and suspicious masses. Simple
cysts are rounded masses of water attenuation (Hounsfield
Radiologic imaging is critical for the successful manage-
ment of renal and extrarenal complications of ADPKD.
Nephrolithiasis, kidney or cyst infections, cyst or retroper-
itoneal hemorrhage, gross hematuria, renal masses, urinary
tract obstruction, and pain are common renal manifesta-
tions of ADPKD. Extrarenal complications include liver
cyst infections, hemorrhage or rupture, intracranial aneurysms,
inferior vena cava or hepatic venous outflow obstruction,
cardiac abnormalities, and abdominal or inguinal hernias. All
of these complications require imaging of at least one modality.
Clin J Am Soc Nephrol 9: 406–415, February, 2014
Renal Complications
Nephrolithiasis occurs in 16%–25% of ADPKD patients
and usually presents with renal colic, microscopic or gross
hematuria, and occasionally, urinary tract obstruction.
Kidney stones are hyperechoic round structures with pos-
terior shadowing on US and hyperdense calcifications on
CT scan. CT is superior to US in detecting small stones and
stones trapped in the ureters. Therefore, the modality of
choice for exploration of kidney stones is high-resolution
CT imaging without contrast. Cyst wall calcifications are
common in ADPKD (Figure 3A) and associate with in-
creased total kidney volume, cyst burden, cyst hemor-
rhage, and chronic pain, but they can be differentiated
from nephrolithiasis on CT imaging (Figure 3B).
Complex cysts are hyperechoic with heterogeneous
intracystic material that is often accompanied by cyst wall
calcifications, intracystic septations, cyst wall thickening, or
enhancement of the contrast media. Complex cysts represent
hemorrhage, infection, or malignancy (15% of renal cell
carcinomas in the general population present as cystic
masses) (19). Hemorrhagic cysts are hyperechoic on US,
hyperdense on CT imaging, and hyperintense T1 signal
on MRI without enhancement after injection of contrast.
Hemorrhagic cysts can cause pain and hematuria. How-
ever, if there is direct communication into the collecting
system, gross or microscopic hematuria may occur with-
out pain (1). Hematuria caused by cyst rupture generally
resolves within 2–7 days with rest, hydration, and dis-
continuation of renin angiotensin aldosterone inhibitors
(20). With unusual and severe bleeding, an angiography
followed by arterial embolization or even nephrectomy
may be necessary (21).
Cyst infection, pyelonephritis, pyocystitis, and perineph-
ric abscesses usually present with localized pain and fever.
The classic triad of fever, pain, and complex renal cyst on
an imaging study (22) is considered diagnostic of cyst in-
fection and can be best detected by MRI (hyperintense T1
signal without enhancement). Blood cultures are positive
in approximately one half of cases, and often, there are no
urinary abnormalities. Therefore, empirical antibiotic ther-
apy is often necessary. The intracystic heterogeneous sig-
nal intensity of infection is difficult to differentiate from a
Figure 3. | Calcifications in autosomal dominant polycystic kidneys. A shows a noncontrast computerized tomography scan of a patient with
autosomal dominant polycystic kidney disease and cyst wall calcifications (arrow). B represents the noncontrast computerized tomography
scan of a 27-year-old man with autosomal dominant polycystic kidney disease and multiple calcified stones in the right kidney (arrows).
Imaging Studies in ADPKD, Rahbari-Oskoui et al. 409
hemorrhagic cyst. As opposed to cyst infections, pyelone-
phritis can be bilateral or diffuse, and it is accompanied
with the sensation of malaise and sickness, high-grade fever,
and chills. An imaging study is not necessary in a typical
presentation of pyelonephritis, unless the patient is resistant
or refractory to treatment or urinary obstruction is suspected.
US or CT can both be used to rule out urinary obstruction,
and positron emission tomography (PET) and dimercapto-
succinic acid scintigraphy are useful for the management
of cyst infections and abscesses that are unresponsive to
therapy. Fludeoxyglucose (18FDG) -PET seems to be diag-
nostically superior to MRI. PET technology uses the avidity
of various tissues and cells to uptake an analog of glucose
(18FDG) to create imaging interface between those tissues.
The use of PET technology in conjunction with CT (PET
scan) or MRI (PET-MRI) provides simultaneous anatomic
and metabolic information. Infected tissues are avid for
glucose and show increased metabolic activity for the
tracer. Importantly, 18FDG-PET scans have been used in
ADPKD patients to diagnose infected kidney and liver cysts
and support CT-guided needle drainage in recurrent or re-
fractory cyst infections (23,24).
Renal cell carcinomas (RCCs) have been reported in
ADPKD but are not conclusively associated with this disease
(25). A recent retrospective study showed a relatively high
frequency (5%) of malignant neoplasms at the time of elec-
tive nephrectomy (26). The Bosniak CT-based categorization
of complex renal cystic lesions in regards to their likelihood
of being RCC is helpful in these cases (Table 2) (27). Class I
and II cysts are considered low risk for malignancy and
followed with interval imaging to measure growth and pro-
gression. Class III and IV cysts are high-risk lesions and
typically require surgical intervention. The use of CT for
this indication is limited by the nephrotoxicity of iodinated
contrast medium, typically in individuals with more ad-
vanced renal insufficiency, and the risks of cumulative radi-
ation exposure, making MRI a better imaging modality for
management of complex renal cysts.
MRI with injection of Gadolinium-based contrast with
fat saturation and the subtraction technique characterizes
complex cysts and renal masses. The typical MRI finding of
an RCC is a heterogeneous mass of low-to-intermediate
410 Clinical Journal of the American Society of Nephrology

Table 2. The Bosniak renal cyst classification system

Category: Criteria Management

IA: Benign simple cyst with a hairline thin wall that does not contain septa, No intervention
calcifications, or solid components; it has water attenuation and does not enhance
IIA: Benign cystic lesion that may contain a few hairline thin septa, in which perceived No intervention
(not measurable) enhancement may be appreciated; fine calcification or a short segment
of slightly thickened calcification may be present in the wall or septa; uniformly
high-attenuating lesions (3 cm) that are sharply marginated and do not enhance are
included in this group
IIB: Cysts may contain multiple hairline thin septa; perceived follow-up (not measurable) Repeated imaging
enhancement of a hairline thin smooth septum or wall can be identified; there may be
minimal thickening of wall or septa, which may contain calcification that may be
thick and nodular, but no measurable contrast enhancement is present; there are no
enhancing soft tissue components; totally intrarenal nonenhancing high-attenuating
renal lesions (3 cm) are also included in this category; generally well marginated
III: Cystic masses with thickened irregular or smooth walls or septa, in which measurable Surgical for histology
enhancement is present; these masses need surgical intervention in most cases, because or resection
neoplasm cannot be excluded; this category includes complicated hemorrhagic or
infected cysts, multilocular cystic nephroma, and cystic neoplasms
IV: Clearly malignant cystic masses that can have all of the criteria of category III but also Surgical resection
contain distinct enhancing soft tissue components independent of the wall or septa

Adopted from reference 27, with permission.

signal on T1-weighted images that increases in signal intensity
on T2-weighted images and intensely enhances after injection
of Gadolinium (28). In contrast, complex cysts do not show
the intense enhancement and disappear on the subtracted
images, which is particularly important in ADPKD, where
complex cysts are common. We have been able to avoid ne-
phrectomies in several ADPKD patients where CT imaging
showed Bosniak stage III and IV complex cysts but MRI con-
firmed the nonenhancing and benign nature of the hemor-
rhagic lesions (Figure 4). Of note, the risk of nephrogenic
systemic fibrosis associated with the use of Gadolinium is
higher when the least stable chelate of Gadolinium (Omnipaq)
was used in ESRD patients (8 patients with nephrogenic
systemic fibrosis [NSF] in 312 patients who received Omnipaq
at Emory University Hospital). With the more stable salts
of Gadolinium (MultiHance), no cases of NSF have been
reported in 784 ESRD patients at our institution (29,30). A
larger study from the United Kingdom showed no cases of
NSF in 2053 patients with CKD (608 patients had CKD stages
4 and 5) who received Gadolinium (31).
Urinary tract obstruction and hydronephrosis are com-
mon and occur because of cyst compression, blood clots, or
obstructing stones. The clinical use of US or CT to detect
obstruction in advanced ADPKD is limited because of the
inability of the collecting system to dilate secondary to
peripelvic cyst compression. However, in the presence of
acute renal failure, US should be the first modality used.
When kidney stones are considered, spiral CT can be per-
formed first. The most reliable imaging modality for uri-
nary obstruction is the Tc99-mercaptoacetyltriglycerine-3
renal scan with a diuretic renography. Furosemide is the
diuretic of choice because of the excellent image quality and
high clearance rates in patients with renal insufficiency
(32). In presence of obstruction, the perfusion phase of the
kidneys is intact and symmetric, but the clearance of the
radiotracer is delayed on the obstructed side, and differences
between the obstructed and nonosbstructed kidney are
increased by the administration of furosemide (Figure 5).
Tc-99M MAG 3 renogram also estimates individual or split
kidney function, which can be particularly helpful in pretrans-
plant and renovascular hypertension workups (3) (Table 3).
Extrarenal Complications in ADPKD
Hepatic cysts are the most common extrarenal manifes-
tation of ADPKD, and they are present in more than 83% of
patients at age 30 years (33). Hepatic cysts arise from both
biliary microhamartomas, which are often large and lo-
cated deep in liver parenchyma, and peribiliary glands,
which surround intrahepatic bile ducts. These cysts are
tiny and surround the hepatic hilum and the larger portal
tract (34–36). Liver cystic disease can range from a few
isolated cysts to massive hepatomegaly. Regardless of
cyst burden, liver function tests are relatively normal,
with the exception of a mildly elevated alkaline phospha-
tase and bilirubin (33). In addition to causing chronic pain
and discomfort, massive hepatomegaly can result in an-
orexia, early satiety, shortness of breath, malnutrition,
and rarely, portal hypertension, variceal bleeding, ascites,
and venous obstruction. Liver cyst infection and rupture
are uncommon and a late complication when the liver is
quite large. Massive hepatomegaly is primarily seen in
women without an obvious familial aggregation and often
seen with relatively modest renal involvement. Pregnancy
has long been suspected to play a role in the acceleration
of liver cyst growth, and isolated cases support this
observation.
Using MR liver imaging with breath-held T2 images and
fat saturation, total hepatic cyst volume can be determined
(37). The distribution of cysts is unequal throughout the
liver, and most patients develop cysts in segments VIII and
VII followed by segments II and IV (23%, 20%, 18%, and
Clin J Am Soc Nephrol 9: 406–415, February, 2014 Imaging Studies in ADPKD, Rahbari-Oskoui et al. 411

Figure 4. | Complex cyst in a patient with autosomal dominant polycystic kidney disease. (A) Axial T2-weighted and axial (B) unenhanced and
(C) enhanced three-dimensional T1-weighted gradient echo magnetic resonance images depict a mass in the lower pole of the left kidney with
(A, arrow) heterogeneous T2 signal intensity and (B, arrow) T1 high signal. After administration of Gadobenate Dimeglumine, there is high
signal on (C, arrow) an enhanced image similar to the (B) unenhanced T1-weighted image. The absence of enhancement on the (D, arrow)
subtraction image supports the diagnosis of complex hemorrhagic cyst and rules out a tumor.

Figure 5. | Mercaptoacetyltriglycerine-3 (MAG-3) renal scintigraphy without and with injection of furosemide in a 33-year-old patient with
autosomal dominant polycystic kidney disease who presented with massive gross hematuria and acute renal failure. A, top, represents the
perfusion phase, and the bottom images show the excretion phase before injection of furosemide. (B) The postfurosemide images show
asymmetric excretion and a higher intensity signal on the right side. The times to peak height of the cortical renogram curves are 2.72 for the left
kidney and 16 for the right kidney. The cortical 20 minutes to maximum ratios are 0.48 for the left kidney and 0.98 for the right kidney. These
results suggest obstruction on the right side, which in this case, was caused by ureteral clots.
412 Clinical Journal of the American Society of Nephrology

Table 3. Recommended imaging modalities based on the type of renal complications in ADPKD

Renal Complication Imaging Modality of Choice

Nephrolithiasis High-resolution computerized tomography

Obstruction
Complex cysts/suspicion of renal cell carcinoma
Infected cysts refractory to treatment
Chronic kidney pain/possible cyst aspiration
Intractable cyst hemorrhage
Ultrasound or Tc99-MAG-3 renal scan (with furosemide)
Magnetic resonance imaging with injection of Gadolinium
Fludeoxyglucose Positron emission tomography scan
Computerized tomography scan
Angiography with selective embolization

ADPKD, autosomal-dominant polycystic kidney disease; MAG-3, mercaptoacetyltriglycerine-3.

Figure 6. | Distribution of liver cysts based on Couinaud’s hepatic segments. Couinaud’s classification of (left) hepatic segmentation with the
(right) distribution of liver cysts in autosomal-dominant polycystic kidney disease patients per each segment.

18%, respectively); segment I presents with the fewest
cysts (5%) (38) (Figure 6).
Complicated liver cysts may be caused by infection or
hemorrhage, and often, they occur in hemodialysis, peri-
toneal dialysis, or post-transplant patients, where liver cyst
growth continues. Diagnostic options are the same as for
renal cysts: CT, MRI, and 18FDG-PET for diagnosis, CT-
guided percutaneous cyst aspiration for those patients who
do not respond to antibiotics, arterial embolization for
intractable bleeding, and surgical fenestration. Partial liver
resection and hepatic transplantation may be necessary in
rare cases of massive hepatomegaly.
Cardiac manifestations are common features of ADPKD.
Valvular heart disease occurs in approximately 18% of cases.
Mitral valve billowing, prolapsed, and regurgitation are pre-
sent in 5.3%, 2.6%, and 7.9% of cases, respectively (39). Al-
though previous echocardiography studies indicated a high
prevalence of left ventricular hypertrophy and increased
left ventricular mass index in both normotensive and hy-
pertensive ADPKD patients, recent cardiac MR imaging
used in 541 ADPKD participants in the Halt Progression
of Polycystic Kidney Disease trials (40) revealed a lower
than expected prevalence of left ventricular hypertrophy
with a frequency of 3.9%. There was a direct association
between left ventricular mass index and systolic BP, serum
creatinine, age, and albuminuria and an inverse association
with women (40).
Both inferior vena cava (IVC) and hepatic venous out-
flow obstruction have been reported in ADPKD patients
with massive liver cystic disease and hemorrhage (41–43).
Doppler US studies of the ilio-femoro-popliteal veins and
MR venogram are used to confirm the diagnosis. IVC
compression because of enlarged renal cysts has also
been reported (44,45). Surgical cyst reduction (after place-
ment of an IVC filter) may be needed to relieve the ob-
struction caused by reaccumulation of cyst fluid after
aspiration (44).
Intracerebral aneurysms (ICAs) are uncommon but an
important associated feature of ADPKD. The prevalence of
ICAs is 2.8% in general population and 5.8% in ADPKD
(46). ICAs are more commonly (77%–84% of cases) found
in the anterior circulation (47,48). ICAs cluster in a small
number of ADPKD families, and a positive family history of
ICA is the only established risk factor associated with ICA in
ADPKD. A ruptured aneurysm carries a combined fatality/
morbidity rate of 35%–55%.
The screening for ICAs can be done by using CT angiog-
raphy, four-vessel arteriography, or MRI (49). All modalities
have excellent accuracy, but given the lack of radiation and
iodinated contrast, MRI is the recommended screening mo-
dality of choice. Magentic resonance angiography with or
without Gadolinium can be used to clearly outline the cere-
bral vasculature. In a rescreening study, ICAs were found in
2.6% over 10 years in 77 patients with an initial negative CT
Clin J Am Soc Nephrol 9: 406–415, February, 2014
Table 4. Recommended imaging modalities based on the type
of extrarenal complications in ADPKD
Extrarenal Imaging Modality
Complication of Choice
Screening for intracerebral MRA without injection
aneurysms of Gadolinium
Cardiac manifestations Echocardiogram
(vlavulopathy–left
ventricular hypertrophy)
Complex cysts/hemorrhagic Identical to renal cysts
or infected cysts
MRA, magnetic resonance angiogram.
angiography (50). The growth of identified ICAs is slow and
uncommon. Only 12% show an increase in diameter greater
than 5 mm over 243 patient-years. Based on these studies and
other familial studies, asymptomatic screening of ADPKD
patients without a family history of ICA is not routinely
recommended, and the rescreening of patients with a pos-
itive family history should only be repeated every 5–10
years. Additional indications for screening include pa-
tients undergoing transplant evaluation, commercial pi-
lots, and patients with considerable concern about their
status.
The management of ICAs in ADPKD patients depends
on size, location, and symptoms. Typically, ICAs,5 mm in
diameter are at low risk of rupture. In symptomatic indi-
viduals or individuals with ICAs greater than 7 mm, either
surgical or coil ablation or thrombosis is recommended,
depending on the size and location of the ICA. Complica-
tions related to surgical intervention are low (,1%) but
have significant morbidity, and they are more common
with ICAs in the posterior circulation of the circle of Willis.
Therefore, patients with ICAs should be properly in-
formed about the risks of rupture and complications of
treatment before deciding to undergo surgical or endovas-
cular interventions (Table 4).
Total Kidney Volume: A Prognostic Marker of Renal
Disease Progression
Renal cyst growth and kidney enlargement are the central
features of ADPKD. The CRISP consortium, developed by
the National Institutes of Health, aimed to determine if MRI
could detect small differences over time in the rate of cyst
growth and whether or not total kidney volume (TKV)
predicted future renal insufficiency (51).
Several important findings from the CRISP study have
emerged. A height-corrected TKV (htTKV) of 600 ml/m
predicts the future development of CKD stage 3 within 8
years. The predictive power of htTKV is better than age,
genotype, serum creatinine, BUN, urinary albumin, or
monocyte chemotactic protein-1 levels (52). The typical
relationship between TKV and GFR measured by iothala-
mate clearance (correlation coefficient r520.29) improves
dramatically when htTKV is compared with kidney func-
tion 8 years later (r520.68). Genotype, sex, age, proteinuria,
and hypertension, all risk factors for progression to renal
failure, are manifested by increased TKV. Although PKD1
Imaging Studies in ADPKD, Rahbari-Oskoui et al. 413
patients show larger TKV (994 versus 678 ml; P,0.001), they
have a similar annual change in TKV (5.51% versus 4.99%
per year in PKD1 versus PKD2, respectively) (53). These
data highlight the importance of TKV as a predictive
marker of disease progression and its prognostic importance
(54).
Conclusions and Recommendations
Radiologic imaging studies provide important diag-
nostic and management guidance in ADPKD. US is the
imaging modality of choice for screening for a diagnosis of
ADPKD. CT imaging is particularly useful in the as-
sessment of pain (to rule out nephrolithiasis, hemorrhagic
renal or hepatic cysts, diverticulitis, etc.), complex renal and
hepatic cysts, and guidance for cyst aspiration procedures.
Renal MRI with injection of Gadolinium should be used to
assess complicated cysts that are suspicious for malignancy.
Particular attention should be paid to potential renal donors,
where CT and MRI have increased sensitivity to detect
cysts,1 cm consistent with simple renal cysts. CT and MRI
may also be better screening options in at-risk individuals
early in the course of their disease. Genetic testing should be
offered to those individuals when imaging studies do not
provide a clear answer with regard to ADPKD. There is
growing evidence to support the importance of htTKV
as a prognostic marker in ADPKD. Cerebral MRA with-
out injection of Gadolinium should be used to detect ICAs
in ADPKD patients with a family history of ICA or stroke.
In the absence of symptoms and with a negative initial
study, repeat MRAs are not needed for at least 5 years.
18FDG-PET scan is particularly helpful when renal or
liver cyst infections/abscesses are suspected. Renal angi-
ography with selective embolization of a renal artery may
be indicated in case of intractable cyst hemorrhage. Tc99-
mercaptoacetyltriglycerine-3 renal scintigraphy is the modal-
ity of choice to rule out renal obstruction and renovascular
hypertension.
Specific imaging modalities support different aspects
of care in ADPKD, and their use and interpretation
by nephrologists and radiologists are essential to opti-
mize the care of these patients and their family members.
Disclosures
F.R.-O., A.M. and P.M. did not receive any financial support. A.C.
is a consultant for Pfizer, Otsuka, and Sanofi.
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