Hematuria

Author: Sanjeev Gulati, MBBS, MD, DNB(Peds), DM, DNB(Neph),

FIPN(Australia), FICN, FRCPC(Canada); Chief Editor: Craig B Langman, MD
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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:

Recognize and confirm the finding of hematuria.

Identify common etiologies.
Select patients who have significant urinary system disease that might require
further expertise in either diagnosis or management and referral

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.

A history of passage of clots in urine suggests an extraglomerular cause of

hematuria.
A history of fever, abdominal pain, dysuria, frequency, and recent enuresis in
older children may point to a urinary tract infection as the cause of hematuria.
A history of recent trauma to the abdomen may be indicative of hydronephrosis.
A history of early-morning periorbital puffiness, weight gain, oliguria, the
presence of dark-colored urine, and the presence of edema or hypertension
suggests a glomerular cause.

Hematuria due to glomerular causes is painless.

A history of a recent throat or skin infection may suggest postinfectious
glomerulonephritis.
A history of joint pains, skin rashes, and prolonged fever in adolescents suggests a
collagen vascular disorder.
The presence of anemia cannot be accounted for by hematuria alone, and, in a
patient with hematuria and pallor, other conditions such as systemic lupus
erythematosus and bleeding diathesis should be considered.
Skin rashes and arthritis can occur in Henoch-Schnlein purpura and systemic
lupus erythematosus.
Information regarding exercise, menstruation, recent bladder catheterization,
intake of certain drugs or toxic substances, or passage of a calculus may also
assist in the differential diagnoses.
Because certain diseases that present with hematuria are inherited or familial,
asking for a family history that is suggestive of Alport syndrome, collagen
vascular diseases, urolithiasis, or polycystic kidney disease is important.

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]

A detailed skin examination is necessary to look for purpura.

An abdominal examination is indicated to look for palpable kidneys (Wilms
tumor or hydronephrotic kidneys).
A careful examination of the genitalia is also important.
A detailed ophthalmological evaluation is helpful in familial hematurias.

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

Acute Poststreptococcal Glomerulonephritis

Anti-GBM Antibody Disease
Endocarditis, Bacterial
Hemolytic-Uremic Syndrome
Henoch-Schoenlein Purpura
Hypercalciuria
IgA Nephropathy
Systemic Lupus Erythematosus
Urinary Tract Infection
Urolithiasis

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.

This test is based on the peroxidase activity of hemoglobin. It can detect

trace amounts of hemoglobin (rather than the presence of RBCs) and
myoglobin. False-positive results can occur (certain dyes or drugs, beets,
oxalates). Briefly dip the strip in the urine, tap off excess urine, and read
the strip at the recommended time (usually 1 min). Dipsticks have a
sensitivity of 100% and a specificity of 99% in detecting 1-5 RBCs per
high-power field (hpf).
o The presence of hematuria is most important to confirm, since both normal
and abnormal causes (eg, hemoglobinuria, myoglobinuria) can produce
false-positive results. Confirmation requires a microscopic examination of
the urine for the presence of RBCs and casts. A freshly voided urine
specimen should be used. A 10- to 15-mL aliquot of the urine is spun in a
centrifuge at 1500 rpm for about 5 minutes. The supernatant is decanted,
and the sediment is resuspended in the remaining liquid. The urine sample
is then carefully examined under high-power magnification. All
noncellular and cellular elements should be noted and recorded. More than
5 RBCs per hpf is generally considered abnormal. RBC casts indicate a
glomerulotubular source of hematuria. The absence of RBCs and RBC
casts despite a positive dipstick test suggests hemoglobinuria or
myoglobinuria.
o Other cellular elements in the urinary sediment (eg, WBCs, WBC casts)
suggest a diagnosis of urinary tract infection. In this latter instance, a urine
culture must be performed to determine the causative organism. Crystals,
bacteria, protozoa, and other elements may also be seen.
o Parents of children with isolated microscopic hematuria should be
reassured that sufficient time remains to plan a stepwise evaluation. Other
investigations should be avoided, and the dipstick and microscopic
urinalysis should be repeated twice within 2 weeks.
Phase contrast microscopy: A careful examination of the urine for the presence of
a significant number of dysmorphic RBCs suggests a renal (glomerular) source of
the hematuria. A urine sample that predominantly contains eumorphic RBCs
suggests an extrarenal (nonglomerular) source. This test has been reported to have
a sensitivity of 83-95% and a specificity of 81-95%. The sensitivity and
specificity may vary from one examiner to another.
BUN/serum creatinine: Elevated levels of BUN and creatinine suggest significant
renal disease as the cause of hematuria.
Hematologic and coagulation studies: CBC counts and, sometimes, platelet counts
may be performed in selected patients with a clear history of a bleeding disorder.
In general, coagulation studies and CBC counts often do not add additional
information in the evaluation of hematuria. In certain populations, a sickle cell
preparation or a hemoglobin electrophoresis may be useful in establishing the
diagnosis of sickle cell disease or trait.
Urine calcium: Hypercalciuria is a relatively common finding in children.
Measurement of the urine calcium excretion using either a timed 24-hour urine
collection for calcium or a spot urine calcium-creatinine ratio can be helpful in
establishing hypercalciuria as a cause of hematuria. A calcium excretion of more

than 4 mg/kg/d or a urine calcium-creatinine ratio of more than 0.21 are

considered abnormal.
Serologic testing: Measuring serum complement levels is important if a
glomerular cause of hematuria is suspected. Low serum complement levels are
seen in postinfectious glomerulonephritis, systemic lupus erythematosus nephritis,
bacterial endocarditis, and membranoproliferative glomerulonephritis. A high
antistreptolysin (ASO) titer suggests a recent streptococcal infection. Anti-DNase
B levels are also indicative of a recent group B streptococcal infection and may be
positive even when the ASO level is normal. This latter statement is relevant in
poststreptococcal glomerulonephritis secondary to a skin infection. Antinuclear
antibody (ANA) titers and the measurement of double-stranded DNA (dsDNA)
levels are most helpful in children with suspected systemic lupus erythematosus
nephritis.
Urine culture: A midstream or clean-catch specimen of urine should be obtained
for culture sensitivity whenever a urinary tract infection is suspected. This is
especially important in younger children, in whom classical symptoms of a
urinary tract infection may be absent.

Imaging Studies
The following imaging studies are indicated:

Renal and bladder ultrasonography: Urinary tract anomalies, such as

hydronephrosis, hydroureter, nephrocalcinosis, tumor, and urolithiasis, are readily
revealed with ultrasonography. Compared with other imaging studies, sonography
is rapid, noninvasive, readily available, and devoid of exposure to radiation. In
individuals with severe obesity, a more accurate definition of renal structures and
surrounding organs can be achieved using only CT scanning.
Other imaging studies
o A spiral CT scan is particularly useful in the detection of urolithiasis,
Wilms tumor, and polycystic kidney disease.
o Voiding cystourethrograms are valuable in detecting urethral and bladder
abnormalities that may result in hematuria (eg, cystitis).
o Radionuclide studies can be helpful in the evaluation of obstructing
calculi.
o Intravenous urography rarely contributes additional information in the
evaluation of hematuria and may unnecessarily expose the child to
ionizing radiation.

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

Gross, intermittent, No specific changes,

painless hematuria although increased
serum

IgA levels observed in

some patients

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

A comprehensive physical examination and a detailed history are indispensable to the

evaluation of hematuria.

A urinalysis should be obtained (as described above), and a careful microscopic

review of the sample should be performed. Examples of microscopic findings are
shown in the images below.

Microscopy of urinary sediment. Typical appearance in non-glomerular hematuria:

RBCs are uniform in size and shape but show two populations of cells because a
small number have lost their hemoglobin pigment.

Microscopy of urinary sediment. Typical appearance of RBCs in glomerular

hematuria: RBCs are small and vary in size, shape, and hemoglobin content.

Microscopy of urinary sediment. A cast containing numerous erythrocytes, indicating

glomerulonephritis.

A positive dipstick reaction should be followed by a urine analysis to confirm the

presence of RBCs and/or casts. The absence of erythrocytes suggests
myoglobinuria or hemoglobinuria, whereas the absence of hemoglobin, red cells,
or myoglobin should prompt a search for other causes of red urine.
The next step in the differential diagnosis is localization of the bleeding. The
presence of red cell casts and preponderance of dysmorphic cells on phase
contrast microscopy are consistent with glomerular bleeding. Other urine
characteristics that help in distinguishing between glomerular and nonglomerular
hematuria are discussed above.
A urine culture should be obtained. Significant bacterial growth, indicative of
urinary tract infection or pyelonephritis, requires antibiotic treatment and,
possibly, further radiologic evaluation of the genitourinary tract for obstruction,
vesicoureteral reflux, cystic disease, and other abnormalities. A urine culture
showing "no growth" may need to be followed by imaging studies. A urine sample

should be sent for determination of the urine calcium-creatinine ratio. An

abnormal result should prompt a 24-hour urine collection to confirm the diagnosis
of hypercalciuria.
If hematuria is of glomerular origin, measurements of protein excretion and
serology tests may be in order. Low C3 levels should suggest
membranoproliferative glomerulonephritis or systemic lupus erythematosus as
diagnostic possibilities. The latter should be confirmed by measurements of ANA
or dsDNA. A low C3 level in association with an elevated ASO titer or antiDNAse B, are indicative of poststreptococcal glomerulonephritis. The
concomitant presence of hematuria and proteinuria often indicates serious renal
disease. A kidney biopsy should be considered if proteinuria is persistent.
The approach to the evaluation of hematuria varies among physicians and no
single method applies in all circumstances. One approach is outlined in the
images below.

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.

The child with a complicated diagnosis or unexplained cause for the

hematuria should be referred to a pediatric nephrologist or, in some cases,
to an appropriate subspecialist. If a diagnosis is straightforward, the
appropriate therapy or follow-up is administered.
o If the child has recurrence of the symptoms and associated hematuria or if
the hematuria is persistent, referral to a pediatric nephrologist is
recommended.
Asymptomatic microscopic hematuria with proteinuria
o In the asymptomatic child, simultaneous microscopic hematuria and
proteinuria (>50 mg/dL) in 3 consecutive urine samples is unusual and
occurred in the Galveston study, with a prevalence of 64 per 100,000
school children (approximately 0.06%).[5] All of the children in this survey
who were thought to have significant renal disease were included in this
group. Despite the obvious concern attendant to this combined finding,
almost 50% of the children who were discovered to have both hematuria
and proteinuria had spontaneous resolution of both findings during the
course of the 5-year follow-up.[6]
o The significance of the renal involvement, in most cases, correlates
directly with the quantity of protein being excreted. Thus, the combination
of asymptomatic microscopic hematuria and proteinuria seems to suggest
that such patients are more likely to have significant renal disease.
o The first step in this category is to quantitate the urine protein at the initial
or follow-up visit. Asymptomatic patients who are found to have both
hematuria and proteinuria in several samples collected over a few weeks
should be referred to a pediatric nephrologist for further evaluation and
recommendations.
Asymptomatic microscopic (isolated) hematuria
o Asymptomatic microscopic hematuria is common in unselected
populations of children. The discovery of hematuria alone in an
asymptomatic child is merely an indication for repeat testing on one or
more occasions.
o The Galveston County epidemiology study found that, of children who
had 3 consecutive urine samples that demonstrated hematuria, only 37%
had hematuria 1 year later.[5] Thus, the cause for the asymptomatic
hematuria had apparently resolved in 63% of the children over the course
of a single year. Significant renal disease was almost nonexistent in
patients in whom hematuria was the only abnormality found.
o In cases involving the development of proteinuria or pyuria, the condition
of isolated asymptomatic hematuria is no longer observed, and other
studies should be performed. If the microscopic hematuria persists
unchanged for more than 1-2 years, a few additional studies may be
indicated.
o One possible entity responsible for such an asymptomatic persistence of
hematuria is idiopathic hypercalciuria or hyperuricosuria.
o Familial or hereditary hematuria, whether benign, nonprogressive (ie,
"thin basement membrane disease"), or progressive (ie, Alport syndrome
o

or one of its variants), is another condition in which, early in the course,

hematuria may be found in the absence of proteinuria.
IgA nephropathy may also present with microhematuria.

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

Further Outpatient Care

Patients with persistent microscopic hematuria should be monitored at 6-month to 12month intervals for the appearance of signs or symptoms indicative of progressive renal

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.