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Background
Hematuria is one of the most common urinary findings that result in children presenting
to pediatric nephrologists. Generally, hematuria is defined as the presence of 5 or more
RBCs per high-power field in 3 of 3 consecutive centrifuged specimens obtained at least
1 week apart. In the office setting, a positive reaction on the urine dipstick test is usually
the first indication of the presence of hematuria. Hematuria can be gross (ie, the urine is
overtly bloody, smoky, or tea colored) or microscopic. It may be symptomatic or
asymptomatic, transient or persistent, and either isolated or associated with proteinuria
and other urinary abnormalities. The role of the primary care physician in the
management of a child with hematuria includes the following:
Pathophysiology
The etiology and pathophysiology of hematuria vary. For instance, hematuria of
glomerular origin may be the result of a structural disruption in the integrity of
glomerular basement membrane caused by inflammatory or immunologic processes.
Chemicals may cause toxic disruptions of the renal tubules, whereas calculi may cause
mechanical erosion of mucosal surfaces in the genitourinary tract, resulting in hematuria.
Epidemiology
Frequency
United States
The prevalence of gross hematuria in children is estimated to be 0.13%. In more than half
of the cases (56%) this is due to an easily identifiable cause. The most common cause
appears to be cystitis (20-25%). Asymptomatic microscopic hematuria is, on the average,
10-fold as prevalent as gross hematuria (1.5%, range 0.4-4.1%, depending on the criteria
used to define hematuria). With repeated evaluations, the prevalence of asymptomatic
microscopic hematuria decreases to less than 0.5%, supporting the notion that most cases
of hematuria in children are transient. The incidence of simultaneous hematuria and
proteinuria is estimated to be only 0.06%, but their coexistence signals significant renal
disease.
Mortality/Morbidity
In general, children with isolated asymptomatic microscopic hematuria tend to do well,
whereas those with associated findings (eg, hypertension, proteinuria, abnormal serum
creatinine levels) are more likely to have serious problems. Because hematuria is the end
result of various processes, the morbidity and mortality rates of the condition depend on
the primary process that initiated it.
Race
The incidence of hematuria in specific racial groups is determined by the primary cause.
For example, idiopathic hypercalciuria is infrequent in black and Asian children, but
relatively common in whites. Conversely, hematuria caused by sickle cell disease is more
common in blacks than in whites.
Sex
Sex may predispose a child to specific diseases that manifest as hematuria. For example,
the sex-linked form of Alport syndrome has a male preponderance, whereas lupus
nephritis is more common in adolescent girls.
Age
Prevalence of certain conditions varies with age.[1] For instance, Wilms tumors are more
frequent in children of preschool age, whereas acute postinfectious glomerulonephritis is
more frequent in the school-aged population. In adults, hematuria is often a sign of
malignancy of the genitourinary tract (eg, renal cell carcinoma, bladder tumors, prostatic
tumors). These conditions are rare in
History
The first step in the evaluation of hematuria is a detailed review of the history and a
thorough physical examination. An attempt should be made to distinguish glomerular
causes of hematuria from extraglomerular ones, as this helps in prioritizing the
investigations.
Physical
In the general physical examination, the most important step is to measure the blood
pressure (with an appropriate-sized cuff) and evaluate for the presence of periorbital
puffiness or peripheral edema.[2, 3]
Causes
Hematuria can be of glomerular or nonglomerular origin. Brown-colored urine, RBC
casts, and dysmorphic (small deformed, misshapen, sometimes fragmented) RBCs and
proteinuria are suggestive of glomerular hematuria. Reddish or pink urine, passage of
blood clots, and eumorphic (normal sized, biconcavely shaped) erythrocytes are
suggestive of a nonglomerular bleeding site.
Potential causes of hematuria in children include the following:
Glomerular hematuria
o Thin basement membrane disease (benign familial hematuria)
o Alport syndrome
o Immunoglobulin A (IgA) nephropathy
o Hemolytic-uremic syndrome
o Postinfectious glomerulonephritis
o Membranoproliferative glomerulonephritis
Lupus nephritis
Anaphylactoid purpura (Henoch-Schnlein purpura)
Nonglomerular hematuria
o Fever
o Strenuous exercise
o Mechanical trauma (masturbation)
o Menstruation
o Foreign bodies
o Urinary tract infection
o Hypercalciuria/urolithiasis
o Sickle cell disease/trait
o Coagulopathy
o Tumors
o Drugs/toxins (nonsteroidal anti-inflammatory drugs [NSAIDs],
anticoagulants, cyclophosphamide, ritonavir, indinavir)
o Anatomic abnormalities (hydronephrosis, polycystic kidney disease,
vascular malformations)
o Hyperuricosuria
o
o
Differential Diagnoses
Laboratory Studies
The laboratory tests ordered for the evaluation of hematuria must be based on the clinical
history and the physical examination. Identification of a glomerular and extraglomerular
etiology of hematuria based on a good history and urine examination can help the
physician to avoid requesting tests that may be unnecessary.
Urinalysis
o Confirming that a child with red-colored urine has hematuria is
mandatory. Dip strip analysis is critically important in patients with dark
or abnormal-appearing urine because several substances may discolor the
urine and give the appearance of hematuria. The urine dipstick test is
currently one of the most useful and sensitive tools in detecting hematuria.
Imaging Studies
The following imaging studies are indicated:
Procedures
A kidney biopsy is rarely indicated in the evaluation of isolated asymptomatic hematuria.
Most studies reveal minimal histopathological abnormalities in such children. In a survey
of pediatric nephrologists in North America, only 5% of responders indicated that they
would perform a kidney biopsy on a child with asymptomatic hematuria. The main
reasons for performing a biopsy in that survey were academic interest, parental pressure
for a diagnosis, and concern for future economic impact on the child. On the other hand,
the simultaneous presence of proteinuria, elevated serum creatinine, hypertension, a
suspicious clinical history, or other imaging/laboratory abnormalities may justify a
kidney biopsy.
Thus, relative indications for performing a kidney biopsy in patients with hematuria are
as follows:
Significant proteinuria
Abnormal renal function
Recurrent persistent hematuria.
Serologic abnormalities (abnormal complement, ANA, or dsDNA levels).
Recurrent gross hematuria.
A family history of end-stage renal disease
Cystoscopy is not generally required in children with nonglomerular hematuria. The only
indication is a suspicious bladder mass revealed on ultrasonography.
Skin biopsy with immunostaining for the 5(IV) chain is particularly useful when
suspicion of X-linked Alport syndrome is high.
Histologic Findings
In most patients, a renal biopsy is either normal or reveals minor changes, such as thin
glomerular basement membranes, focal glomerulonephritis, or mild mesangial
hypercellularity. In a minority of patients, histologic findings, together with historical or
serologic data, may point to specific conditions
Condition
Systemic lupus
erythematosus
IgA nephropathy
Histology
Mild glomerulitis,
proliferative changes,
immune complex
deposition, crescents,
immunoglobulin
deposition
IgA deposition in the
mesangium, glomerular
sclerosis, proliferative
changes, crescents in
severe cases
History
Hematuria,
proteinuria,
hypertension, joint
pains, rashes
Laboratory Data
Abnormal C3, C4,
ANA, and dsDNA
levels; anemia;
thrombocytopenia
Henoch-Schnlein
purpura
Alport syndrome
Same as IgA
nephropathy
Purpura, joint
pains, abdominal
pain, hematuria
Some thinning of
Sensorineural
basement membranes, hearing loss,
"basket weave" changes corneal
in the glomerular
abnormalities,
basement
hematuria, renal
failure
No specific laboratory
data
No specific changes
membrane on electron
microscopy
Thin basement
membrane disease
Mesangiocapillary
glomerulonephritis
Average glomerular
basement membranes
reported to be 100-200
nm in children in this
condition
Glomerular lobulations,
thickening of the
mesangial matrix and
glomerular basement
membranes, crescents
Persistent
No specific changes
microscopic or
gross hematuria,
significant family
history
Hematuria,
C3 levels possibly
proteinuria,
abnormal
hypertension
Approach to hematuria.
Nonglomerular hematuria.
Glomerular hematuria.
Staging
Categorizing patients with hematuria into one of the following groups is helpful:
Gross hematuria
o Gross hematuria is alarming for the child's parents and sometimes for their
pediatricians.
o Gross hematuria is an uncommon finding in an unselected population of
children. The prevalence of gross hematuria was reported as 0.13%, based
on a retrospective review of children seen in an emergency walk-in clinic.
o Most children with gross hematuria (56%) have an easily recognizable and
apparent cause. The most common diagnoses include urinary tract
infection, perineal irritation, trauma, meatal stenosis with ulceration,
coagulation abnormalities, and urinary tract stones.
o Less than half (44%) of children with gross hematuria had a cause that
was either not obvious or that required additional or more sophisticated
examinations. Among the diagnoses in this group are recurrent gross
hematuria, acute nephritis, ureteropelvic junction obstruction, cystitis
cystica, epididymitis, tumor, hyperuricosuria, and hypercalciuria.
o These children require referral to a pediatric nephrologist for detailed
investigation and management.
Microscopic hematuria with clinical symptoms
o A child who presents with either symptoms of an illness or a physical
abnormality and is discovered to have concurrent microscopic hematuria
should be placed in this category.
o Some of the clinical conditions with associated renal involvement that
may be recognized by the primary physician are acute glomerulonephritis,
acute interstitial nephritis, urinary tract infections, familial hematuria (both
benign recurrent and progressive hereditary nephritis), Henoch-Schnlein
purpura, systemic lupus erythematosus, hypertension, hypercalciuria, and
urolithiasis.
o Unless the patient falls into a clear category of illness that is easily
identified, an early consultation with the pediatric nephrologist should be
obtained, because most other illnesses require additional expertise in either
delineation or management.
o The child with microscopic hematuria associated with clinical symptoms
may have a vast number of diseases or conditions, which makes this a
difficult category for which to suggest specific evaluation.
o The first step in this category is to direct the evaluation based on the
symptoms or physical examination findings. The extent and thoroughness
of the evaluation depends on the knowledge and experience of the
physician.
Medical Care
Asymptomatic (isolated) hematuria generally does not require treatment. In conditions
associated with abnormal clinical, laboratory, or imaging studies, treatment may be
necessary, as appropriate, with the primary diagnosis.
Surgical intervention may be necessary in certain anatomical abnormalities, such as
ureteropelvic junction obstruction, tumor, or significant urolithiasis
Consultations
Consultations are required in patients with urinary tract anomalies and in some patients
with systemic diseases (eg, bleeding disorders, collagen vascular diseases, sickle cell
nephropathy).
Diet
Dietary modification is usually not indicated except for children who may have a
tendency to develop hypertension or edema as a result of their primary disease process
(eg, nephritis). In these patients, a low sodium diet may be helpful. In addition, a diet
containing the recommended daily amount (RDA) for calcium plus a low-salt diet may be
beneficial in children with hypercalciuria and hematuria.
Activity
Activities of a child with asymptomatic, isolated hematuria should not be restricted.
However, these children and their parents should be informed that strenuous exercise may
aggravate hematuria. Restrictions in physical activities may be indicated in children with
severe hypertension or cardiovascular disease.
Medication Summary
Hematuria is a sign and not a disease. Therapy should be directed at the process causing
hematuria
disease. Prominent among them are proteinuria, hypertension, and a decrease in renal
function.
Prognosis
The prognosis of patients with asymptomatic isolated hematuria is good. The ultimate
prognosis for the various conditions associated with hematuria depends on the primary
medical condition that caused the hematuria in the first place.
Patient Education
Inform children and their parents that strenuous exercise may aggravate hematuria;
however, hematuria by itself should not prevent the child from participating in sports.
Despite the sometimes alarming intensity or persistence of hematuria, parents must be
informed that, by itself, hematuria rarely causes anemia.