Hematuria in children can be detected by urinary dipstick or microscopic examination. Common causes include glomerular disease, hypercalciuria, and nutcracker syndrome. Evaluation depends on whether hematuria is isolated, accompanied by proteinuria, or symptomatic. For isolated hematuria, follow-up includes urine culture and screening for hypercalciuria if persistent. Hematuria with proteinuria warrants further testing including serum creatinine. Symptomatic hematuria evaluation includes history, physical exam, and urinalysis to determine glomerular vs extraglomerular cause. Renal biopsy is considered if hematuria is substantial or progressive.

1. Hematuria
In children
By Doctor
Yahea Zakarei

2. Hematuria
DETECTION — presence of an increased
number of red blood cells (RBCs) in the
urine. Hematuria can either be visible to the
naked eye (gross) or apparent only upon
urinalysis (microscopic).

3.  Urinary dipstick — The most common screening
test. These strips can detect 5 to 10 intact RBCs/µL,
which roughly corresponds to a finding on microscopic
examination of 2-5 RBCs /HPF from the sediment of a
centrifuged 10 to 15 mL urine sample.
False-negative in the presence of formalin or high
urinary concentration of ascorbic acid.
False-positive with alkaline urine (ie, pH greater than
9) or contamination with oxidizing agents used to
clean the perineum.

4. Microscopic examination
Sediment of 10 to 15 mL of centrifuged fresh urine.
Microscopic hematuria = presence of more than
five RBCs per high-power field .

5. glomerular disease
 Red cell casts .
 Protein excretion greater than 100 mg/m2 at a time
when there is no gross bleeding. The optimal method
is obtaining a first morning sample to determine the
protein to creatinine ratio because it excludes
orthostatic proteinuria, a normal variant.
 Red blood cells (RBCs) having a dysmorphic
appearance.

6. Red cell casts

7. Morphologic study of urinary RBCs
By phase-contrast microscope, The presence of more
than 30 %dysmorphic RBCs or of more than 5 % of a
specific form named an "acanthocyte" is highly
suggestive of glomerular hematuria .
In nonglomerular hematuria, RBCs with a uniform
normal size and shape .
Hypercalciuria, can be associated with dysmorphic red
blood cells but not red cell casts.

8. ETIOLOGY
Both benign and serious conditions can cause
microscopic hematuria in children. The most common
causes of persistent microscopic hematuria include;
glomerulopathies
hypercalciuria
nutcracker syndrome

9. IgA nephropathy
Diagnosed by renal biopsy . mesangial IgA deposits on
immunofluorescence study. There is often a history of
gross hematuria preceded by an URTI or
gastrointestinal illness and usually a negative family
history of renal disease.

10. Alport syndrome
Classic Alport syndrome (hereditary nephritis) is a recessive
X-linked disorder that is typically seen in males and is
often accompanied by high-frequency sensorineural
hearing loss, ocular abnormalities including anterior
lenticonus, and, over time, progressive renal failure.
Heterozygous carrier-females also can have hematuria, but
do not have progressive renal disease. The genetic
abnormality in these patients involves the gene for the
alpha-5 chain of type IV collagen (COL4A5). In addition,
there are autosomal recessive and dominant forms of
Alport syndrome with mutations in the COL4A3 and
COL4A4

11. Thin basement membrane disease
(TBM)
TBM, also called benign familial hematuria, is an
autosomal dominant condition. Kidney biopsy reveals
an isolated thinning of the glomerular basement
membrane on electron microscopy. In many cases,
TBM disease is the heterozygous form of autosomal
recessive Alport syndrome.

12. Postinfectious glomerulonephritis —hematuria
generally resolves within three to six months after the
presentation.
.

13. Hypercalciuria —defined as a urine calcium/creatinine
ratio >0.2 (mg/mg) in children older than six years of
age, has been associated with asymptomatic
microscopic hematuria. the prevalence has ranged
from as low as 11 % in the Northeast to as high as 35 %
in the South. Thus, the association between
hypercalciuria and hematuria may be more common
in areas where there is a higher prevalence of
nephrolithiasis

14. Nutcracker syndrome — Left renal vein compression
between the aorta and proximal superior mesenteric
artery, has been suggested as a cause of hematuria in
children that is usually asymptomatic but may be
associated with left flank pain.
Detected by Doppler ultrasonographic assessment of
left renal vein diameter and peak velocity.
Nutcracker syndrome can also cause orthostatic
proteinuria in children .
nutcracker syndrome highest in Asia

15. EVALUATION
The diagnostic evaluation depends upon the clinical
presentation, which falls into the following three
categories:
1. Asymptomatic isolated microscopic hematuria
2. Asymptomatic microscopic hematuria with
proteinuria
3. Symptomatic microscopic hematuria

16. Asymptomatic isolated
microscopic hematuria
ie, no proteinuria
 Evaluation including blood pressure and a GUE performed
weekly for 2wk. One should ensure that there is no exercise prior
to obtaining the urine sample, since vigorous exercise can induce
hematuria.
 If isolated hematuria persists, obtain a urine culture. If the
culture is positive, treat with appropriate antibiotics.
 If the patient remains asymptomatic and the urine culture is
negative, continue to observe the patient every3-6 mo including
physical examination with blood pressure measurement and
GUE.
 If the asymptomatic isolated hematuria persists for one year, the
following subsequent evaluation should be performed:

17. Measure urine calcium/creatinine ratio for
hypercalciuria.
Test parents and siblings for hematuria to detect
possible thin basement membrane disease (autosomal
dominant) or hereditary nephritis (mostly X-linked
recessive).
Consider hemoglobin electrophoresis if there is a
clinical suspicion for sickle cell trait. Perform
Doppler ultrasonography for the "nutcracker
syndrome".

18. Asymptomatic microscopic
hematuria and proteinuria
The combination of hematuria and proteinuria is associated with a higher risk
for significant renal disease.
Evaluation ; S cr and proteinuria ( by a 24-hour urine collection or urine
protein-to-creatinine ratio on a first morning urine sample) .
If protein excretion is >4 mg/m2 /hr or if in a first morning urine specimen,
the urine protein-to-creatinine ratio is >0.2 mg protein/mg creatinine in
children older than 2 years of age and >0.5 mg protein/mg creatinine in
younger children it is likely that there is significant renal disease.
If protein excretion is less than the above values, reevaluated in 2-3 WK.
If the hematuria and proteinuria have resolved, no further evaluation is
needed.
If there is only asymptomatic microscopic hematuria, the patient is
monitored in the same fashion as asymptomatic isolated microscopic
hematuria.

19. If proteinuria is persistent the patient should be referred
for further evaluation.
Further assessment should include microscopic
examination of the urine by an experienced clinician,
serum creatinine, C3, C4, albumin, and complete
blood count. ASO titer, streptozyme testing,
antinuclear antibody testing, imaging, and renal
biopsy.

20. Symptomatic microscopic
hematuria
The evaluation ; The clinical manifestations; may be
nonspecific (eg, fever, malaise, weight loss)
Extrarenal (eg, rash, purpura, arthritis),
Related to kidney disease (eg, edema, hypertension,
dysuria, oliguria).
The presence of nonspecific or extrarenal manifestations
suggests a systemic process such as lupus nephritis or
Henoch-Schönlein purpura.
Renal causes of symptomatic microscopic hematuria
include glomerular or interstitial diseases of the kidney,
lower urinary tract disease, nephrolithiasis, tumors, and
vascular disease.
The urinalysis can be helpful in differentiating between
glomerular and nonglomerular causes of bleeding

21. Historical clues
Re
cent trauma.
A history of incontinence, dysuria, frequency, or
urgency ( suggests UTI).
unilateral flank pain that radiates to the groin (a
calculus or blood clot).
Flank pain without radiation but with fever, dysuria,
and frequency and/or urgency ( acute pyelonephritis).
History of pharyngitis or impetigo 2-3 wks prior to
onset of hematuria( poststreptococcal
glomerulonephritis).

22. Recent upper respiratory (one or two days prior to onset of
hematuria) infection can be associated with IgA
nephropathy.
A history of predisposing or preexisting clinical conditions
such as sickle cell disease or trait, a coagulopathy such as
severe hemophilia, or deafness (Alport syndrome).
A family history of hematuria, kidney disease (eg, Alport
syndrome or thin basement membrane nephropathy), or
kidney stones.
Exposure to medications that can cause interstitial
nephritis, although hematuria is not typically the central
manifestation in such patients.

23. Physical examination — examination should include
measurement of blood pressure, assessment for edema
and recent weight gain, close skin examination (eg,
purpura), direct visualization of the genitals (looking
for penile urethral meatal erosion or female introitus
pathology), and evaluation for abdominal discomfort
or masses (eg, Wilms' tumor).

24. Urinalysis — Examination of the urine may suggest an
underlying etiology and potential site of bleeding
(glomerular versus extraglomerular). Glomerular
causes of symptomatic hematuria include IgA
nephropathy, Alport syndrome, and postinfectious
glomerulonephritis

25. Further evaluation
 Trauma history —CT scan of the abdomen and pelvis.
 Signs or symptoms of UTI —on urinalysis .include positive
dipstick tests for leukocyte esterase and/or nitrite, more
than 5 WBC per high-power field and the presence of
bacteria on a Gram stain of urine.
 Adenovirus should be considered as a potential etiology
if urinary symptoms and urinalysis suggestive of infection
but the culture is negative.
 Signs or symptoms of perineal/meatal irritation —
Supportive care and reassurance.

26.  Signs or symptoms of nephrolithiasis — Renal
ultrasonography. Abdominal plain films.
 Spiral CT scan is the most sensitive imaging
modality. However, because of concerns related to
radiation exposure, it is not typically the initial test in
young children as it is in adolescents and adults.
Consultation with radiology may be warranted in
younger children to determine the risk-to-benefit ratio
of the test.

27. glomerular disease —( proteinuria, RBCcasts, edema,
and hypertension )
Evaluation; serum creatinine, CBC, C3, C4, and serum
albumin.
Other tests to consider based upon the history and the
physical examination include ASO titer, streptozyme
testing, and antinuclear antibody testing.

28. Indications for renal biopsy
1- Biopsy is not performed for isolated microscopic
hematuria.
2- Considered if substantial or progressive ;
Elevation in the creatinine concentration,
Significant proteinuria,
Unexplained rise in blood pressure even when the
values remain within the normal range.
3- Child with persistent glomerular hematuria, in
whom the parents are worried about the diagnosis
and prognosis.

29. 4- Child with microscopic hematuria and a family
history of kidney failure in early adulthood in a first
order relative.
5- Patients with clear evidence of poststreptococcal
glomerulonephritis represent an exception to these
general recommendations, since gradual
spontaneous recovery is the rule, although
proteinuria may gradually return to normal over
many years.

30. Cystoscopy — is rarely indicated for hematuria in
children. for bladder mass noted on ultrasound and
those with urethral abnormalities due to trauma.