Microscopic hematuria in children

Abstract

The occurrence of microscopic hematuria (microhematuria) in children often causes concern for parents, patients, and physicians. The condition is usually benign in nature, so unnecessary laboratory tests should be avoided. A detailed history and physical examination must be undertaken, but a complete urinalysis with a microscopic examination is usually the only laboratory test required. The differential diagnosis of microhematuria is extensive, but the most important differentiating feature is the presence or absence of proteinuria. Urologists should ensure that serious conditions are not overlooked, unnecessary tests are not performed, and parents are properly reassured. However, there is still no consensus on the standard evaluation that should be used to determine microhematuria in children. The aim of this article is to provide a brief review of microhematuria in children and suggest a stepwise approach that can be used to detect major and/or treatable problems while avoiding unnecessary tests.

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Microscopic hematuria in children
q
CME
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Hui-Ming Chung
a
,
*
, Yung-Ming Liao
a
, Yung-Chen Tsai
a
, Ming-Chen Liu
b
a
Department of Urology, Mennonite Christian Hospital, Hualien, Taiwan
b
Department of Nephrology, Mennonite Christian Hospital, Hualien, Taiwan
article info
Article history:
Received 16 January 2011
Accepted 4 March 2011
Available online 15 September 2011
Keywords:
children
hypertension
mass screening
microscopic hematuria
proteinuria
abstract
The occurrence of microscopic hematuria (microhematuria) in children often causes concern for
parents, patients, and physicians. The condition is usually benign in nature, so unnecessary laboratory
tests should be avoided. A detailed history and physical examination must be undertaken, but
a complete urinalysis with a microscopic examination is usually the only laboratory test required. The
differential diagnosis of microhematuria is extensive, but the most important differentiating feature is
the presence or absence of proteinuria. Urologists should ensure that serious conditions are not
overlooked, unnecessary tests are not performed, and parents are properly reassured. However, there is
still no consensus on the standard evaluation that should be used to determine microhematuria in
children. The aim of this article is to provide a brief review of microhematuria in children and suggest
a stepwise approach that can be used to detect major and/or treatable problems while avoiding
unnecessary tests.
Copyright Ó2011, Taiwan Urological Association. Published by Elsevier Taiwan LLC.
1. Introduction
Microscopic hematuria (microhematuria) is a worrisome clinical
condition that usually prompts a patient to visit to a physician.
Biannual mass urinary screenings of school children have been
performed in Taiwan by the Chinese Foundation of Health since
1990.
1
As a result, many children with microhematuria are identi-
fied and referred to urologists on an annual basis.
2
Therefore,
urologists must be familiar with the management of micro-
hematuria in children. The major causes of microhematuria differ
between children and adults, and the evaluation of this condition
should reflect these differences. Renal disease is more common in
children, while malignancies are more common in adults. The use
of laboratory tests, radiological studies, and cystoscopy are well
established for diagnosing adults, but the results are more variable
in children. Follow-up examination for microhematuria after
a negative evaluation is becoming less common in adults, but
should remain as routine for diagnosing children.
3
This article
provides a brief review of the signs and symptoms of micro-
hematuria in children and proposes a stepwise approach for
treating this medical condition.
2. Definition
Gross hematuria is visible to the naked eye, but microhematuria
is typically detected by a dipstick via a reaction betweenperoxidase
and hemoglobin. However, hematuria must be differentiated from
pigmenturia, either hemoglobinuria or myoglobinuria, by micro-
scopic examination of the urinary sediment.
Hematuria is defined by several parameters, the most common
of which is the presence of 6 red blood cells (RBCs)/mL of urine in
a counting chamber or 2 RBCs/high-power field (hpf) of urinary
sediment.
4
There is still no consensus on the definition of micro-
hematuria, although more than 5e10 RBCs/hpf is usually consid-
ered significant.
5,6
Some authors recommend that at least two of
three urinalyses indicate microhematuria over a period of 2e3
weeks before performing further evaluations.
7,8
3. Classification
In children with microhematuria, the presence or absence of
clinical symptoms may help localize the source of the hematuria. For
example, dysuria, changes in urinary frequency, enuresis, and
bladder spasms suggest the presence of a lower urinary tract irri-
tation (UTI). However, the signs and symptoms of glomerular
disease may include edema, hypertension, abnormal creatinine
levels, arthralgia, rashes, anemia, or hypoalbuminemia. Micro-
hematuria may occur with or without proteinuria. Therefore, three
categories of microhematuria have been proposed: (1) asymptom-
atic, isolated microhematuria, (2) asymptomatic microhematuria
*Corresponding author. Department of Urology, Mennonite Christian Hospital,
44 Min-Chuan Road, Hualien 970, Taiwan.
E-mail address: hchung@jhsph.edu (H.-M. Chung).
q
There are two CME questions based on this article.
Contents lists available at SciVerse ScienceDirect
Urological Science
journal homepage: www.urol-sci.com
1879-5226 Copyright Ó2011, Taiwan Urological Association. Published by Elsevier Taiwan LLC.
doi:10.1016/j.urols.2011.08.001
Urological Science 22 (2011) 93e96
Open access under CC BY-NC-ND license.
Open access under CC BY-NC-ND license.

with proteinuria, and (3) microhematuria with clinical symptoms. In
addition, microhematuria can be intermittent or persistent.
4. Incidence and prevalence
Depending on the definition used for making the diagnosis,
the incidence and prevalence of microhematuria vary greatly in
different reports. In school children, the incidence of micro-
hematuria wasestimated to be 0.41% when four urine specimens per
child were collected; however, the incidence was 0.32% in girls and
0.14% in boys when five consecutive urine samples were analyzed
over a period of 5 years. The prevalence of microhematuria among
school children (6e15 years of age) is estimated to be 1e2%.
5,9
A
screening program in Korea reported that the prevalence of micro-
hematuria among 5 million schoolchildren is 0.8%.
10
In contrast,
a screening studyof 160,000 junior high children in Japan found that
the prevalence of isolated microhematuria is as low as 0.15%.
11
5. Pathophysiology
Hematuria may originate from the glomeruli, renal tubules,
interstitium, or the urinary tract (including the collecting system,
ureter, bladder, or urethra). Unlike adults, in children the source of
bleeding isthe glomeruli more oftenthan the urinary tract. RBCs may
cross the glomerular endothelialbarrier and enter the capillarylumen
through structural discontinuities in the capillary wall.
12
As with any
form of glomerulonephritis, proteins, RBC casts, and deformed RBCs
may accompany hematuria. In patients with hemoglobinopathy, or
those who have been exposed to toxins, the renal papillae are
susceptible to necrotic injury from microthrombi and anoxia. Tran-
sientepisodes of microhematuria, or evengross hematuria,may occur
during systemic infections or after moderate exercise in patients with
renal parenchymal lesions. This may result from renal hemodynamic
responses to exercise or fever via undetermined mechanisms.
13
6. Differential diagnosis
There are various causes of microhematuria in children. The
most common causes include benign familiar hematuria, hyper-
calciuria, immunoglobulin A (IgA) nephropathy, sickle cell traits,
anemia, and complications due to a transplant. Less common cau-
ses include Alport’s nephritis, post-infectious glomerulonephritis,
trauma, exercise, renal stones, and Henoch-Schonlein purpura.
Certain drugs and toxins (e.g., aspirin, sulfonamide, lead, etc.),
coagulopathies, UTIs, tuberculosis, tumors, vascular malformations,
structural anomalies, any form of glomerulonephritis, and lupus
nephritis may occasionally cause microhematuria.
14
Although the differential diagnosis for microhematuria is
extensive, the most important differentiating feature is the pres-
ence or absence of proteinuria. Persons with significant proteinuria
require rapid evaluation and early referral to a nephrologist. Those
persons who do not have proteinuria should receive a follow-up
examination and stepwise evaluation.
4
7. Management
7.1. History
Changes inurinary frequency or urgency, dysuria, or flank
pain may indicate a UTI. Transient hematuria may be associated
with recent trauma, strenuous exercise, menstruation, or
bladder catheterization. A history of a recent sore throat or skin
infection suggests post-infectious glomerulonephritis. Exposure
to certain drugs or toxins, including amitriptylene, anticoagu-
lants, aspirin, chlorpromazine, ritonavir, indinavir, carbon
monoxide, mushrooms, sulfonamide, tin compounds, lead, and/or
phenol, may cause microhematuria. In addition, a family history
of hematuria, hearing loss, hypertension, nephrolithiasis, renal
diseases, renal cystic diseases, hemophilia, sickle cell traits, dialysis,
and organ transplants should also be determined and evaluated.
7.2. Physical examination
The presence of elevated blood pressure usually indicates
a more serious nephrological problem that requires further evalu-
ation. UTIs are often accompanied by fever or costovertebral angle
tenderness. A palpable abdominal mass suggests the presence of
a tumor, hydronephrosis, multicystic dysplastic kidney, or poly-
cystic kidney disease. Coexistence with rashes or arthritis suggests
Henoch-Schonlein purpura and/or systemic lupus erythematosus.
Edema is an important sign of nephrotic syndrome.
7.3. Laboratory tests
For a child suspected of having microhematuria, only two
diagnostic tests are required. The first is a test for proteinuria that
may indicate glomerulonephritis or nephrotic syndrome, and the
second is a microscopic examination of the urine for RBC casts
that may indicate a glomerular source of the hematuria. Phase-
contrast microscopy and particle-size discrimination might be
able to distinguish between glomerular and non-glomerular
sources of hematuria. However, the identification of dysmorphic
RBCs rarely offers additional information that is helpful in
managing microhematuria.
15,16
7.4. Indications for prompt evaluation
A prompt evaluation should be undertaken following the
discovery of any of the following findings: hypertension, edema,
oliguria, significant proteinuria (>500 mg/24 hours), or RBC casts
in the urine. This evaluation should include a complete blood count
(to diagnose hemolytic-uremic syndrome), throat culture, strep-
tozyme panel, and determination the serum C3 concentration (to
diagnose acute post-streptococcal glomerlonephritis) and serum
creatinine and potassium concentrations (if renal insufficiency has
been determined); 24-hour urine collection, in order to determine
protein, creatinine, and calcium levels, should also be performed if
the diagnosis remains unclear.
13
Referral to a pediatric nephrologist
should be considered if the above evaluations suggest a potentially
serious nephrological problem.
7.5. Imaging studies
Renal ultrasonography, as a noninvasive screening test, provides
valuable information regarding the presence of stones, tumors,
hydronephrosis, renal parenchymal dysplasia, structural anomalies,
renal diseases, and bladder anomalies. Although the amount of
information that can be provided by renal ultrasonography for the
evaluation of microhematuria in children remains undetermined,
the cost and time may be justified in terms of reassurance
purposes.
17
Renal ultrasonography may be adequate for most
children with microhematuria because the most common diag-
noses include benign familial hematuria, idiopathic hypercalciuria,
IgA nephropathy, and Alport’s syndrome.
18
A more extensive
evaluation is only required if proteinuria or other indicators are
present. Other commonly used urological imaging studies, such as
intravenous pyelography, voiding cystourethrography, renal
nuclear scans, and cystoscopy, rarely yield useful information for
the treatment of microhematuria and should not be routinely used
for the evaluation of microhematuria in children.
13,17
H.-M. Chung et al. / Urological Science 22 (2011) 93e9694

7.6. Renal biopsy
Renal biopsies rarely yield additional information that can be
used to manage children with isolated microhematuria, except for
those with documented episodes of gross hematuria or a close
relative with a history of hematuria.
13
In a study of 155 children
with isolated microhematuria (excluding non-glomerular causes of
hematuria), renal biopsies revealed no clinically significant findings
that required therapy. More than two-thirds of the biopsies indi-
cated a thin basement membrane, Alport’s syndrome, or IgA
nephropathy, none of which have specific therapies. The remaining
third of the biopsies indicated normal or insignificant findings.
19
The algorithm for evaluating a child with microscopic hematuria
is shown in Figure 1. If there are no indications that require
immediate intervention after a stepwise evaluation, the parents
should be reassured that there are no life-threatening problems,
such as cancer, leukemia, or chronic kidney damage, and that most
cases of isolated microhematuria in children do not warrant
treatment; yearly urinalysis should be adequate for managing the
patient’s condition.
4
However, further evaluation is warranted if
changes occur in the child’s condition.
8. Conclusions
Microhematuria is prevalent in children and worrisome to
parents and patients. Even though not all children require the same
evaluations, a detailed history and physical examination must
always be undertaken. A complete urinalysis with a microscopic
examination is the only laboratory test that is uniformly required of
these children. The remaining evaluations should be tailored
according to the patient’s medical history, physical examination,
and abnormal findings on urinalysis. Most causes of micro-
hematuria in children indicate medical conditions that usually
require referral to a pediatric nephrologist. Indications that require
referral to a urologist are less common, but include obstructing
stones, renal injury from trauma, and anatomical anomalies.
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