‫بسم هللا الرحمن الرحيم‬
HEMATURIA
ABDULLAH AL SALLOUM
Professor and Consultant of Pediatric Nephrology
College of Medicine King Saud University
King Khalid University Hospital
Riyadh, Saudi Arabia
HEMATURIA
• Hematuria is a common finding on urinalysis
with a prevalence rate between 1% and 2%,
and is more common in girls. Majority is
benign.
• Is the presence of blood in the urine and not
only the color.
• Is the main presentation of patient with renal
disease.
HEMATURIA
Presentations of Hematuria
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Gross hematuria
Microscopic hematuria with clinical symptoms
Asymptomatic microscopic (isolated) hematuria
Asymptomatic microscopic hematuria with
proteinuria (most alarming). Proteinuria is
always an indication of a serious condition.
– Any patient with proteinuria and hematouria should
be dealt with immediately because the protein is toxic
to the kidney.
HEMATURIA
Diagnosis:
• Dipstick (urine strip test).
– The most sensitive test for detecting the presence of blood
in the urine, is abnormal urine strip test.
– Up to 3 RBC/HPF can be detected (2-5RBC/HPF).
– Can give you a false positive or false negative if it has high
specific gravity but rarely.
– Should be done in the nephrology ward because if you do it
in the lab it will lyse and give you a wrong reading.
– > 5 RBC/HPF in children or 10 in adults is significant for
hematuria. Check it on 3 different occasions. Must check it
again in 3 weeks if positive then it is pathological. And if
positive you have to confirm by microscopy.
HEMATURIA
Urine Strip Test:
• The reagent utilizes the pseudoperoxidaze
activity of hemoglobin (or myoglobin) to
catalyze a reaction between hydrogen
peroxide and the chromogen
tetramethylbenzidine to produce an oxidized
chromogen, which has a green blue color.
HEMATURIA
Urine Strip Test:
Strips can detect concentration of 2-5
RBC/HPF
HEMATURIA
False negative urine dipstick:
• High specific gravity urine
• High ascorbic acid concentration in the urine.
False positive urine dipstick:
• Delayed reading
• Cross contamination of urine from other
chemicals such as oxidized agent, (household
bleach)
HEMATURIA
Confirmation of hematuria
Urine Microscopy:
• Centrifuge 10 ml of urine for 5 minute
• Decant the supernatant
• Re-suspend the sediment in 0.5 ml of urine
• Place on a slide with a cover slip
• Count the number of RBC. In 20 fields and report the
average
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Positive Test: > 5 RBC/HPF
HEMATURIA
Definition of hematuria:
• 5 RBC’s /HPF in three of three consecutive,
fresh, centrifuged urine specimens obtained
at least 1 week apart.
HEMATURIA
Localization of hematuria:
• Limits diagnostic possibilities for patients and prevent
unnecessary testing.
• Must know if the blood is coming from the kidney or
lower tract (ureter, urethra, bladder).
• If blood comes from the kidney (parenchyma and
calyces), it is mostly associated with proeinuria and
blood clots.
• Lower tract is rarely associated with proteinuria usually
fresh blood.
HEMATURIA
Classification:
• Glomerular hematuria (most serious).
• Non-Glomerular hematuria (mostly benign
in children unlike in adults where it mostly
indicate malignancy)
HEMATURIA
Glomerular hematuria, Clinical presentation:
• Oliguria (<1 ml/kg/hr).
– Polyuria (>5 ml/kg/hr), normal urination (2-4 ml/kg/hr), and
anuria (no urine). These are not normally seen in glomerular
hematuria.
• Presents with edema due to protein interstitial leak and
retention and activation of the renin angiotensin system.
– Systemic disease like SLE and HSP (more common in children.
Presents with arthritis, skin rash, and hematuria).
• Hypertension due to renin angiotensin aldosterone
activation.
• Symptoms of systemic disease (e.g. arthritis, rash).
HEMATURIA
Glomerular hematuria:
• Brown tea, cola-colored urine.
– Brown because the blood is old because it goes a long path and is
sequestered epithelium
• Concomitant proteinuria
• Cellular cast (collection of RBC or WBC in a protein mesh),
always indicates serious pathology (glomerular hematuria)
• Dysmorphic erythrocytes in phase-contrast microscopy
(which is a special test). > 15% abnormal RBC is significant
for glmerularnephritis not cystitis or urethritis. (golmerular
disease).
• Low MCV of erythrocyte by automated analyze
HEMATURIA
RBC CASTS:
RBC casts are best visualized at the edges of
the cover slip and tend to dissolve in urine
of high PH.
HEMATURIA
Causes of Glomerular hematuria:
1. Post-infectious glomerulonephritis (most common).
2. IgA nephropathy (common in Asians, only renal
presentation unlike HSP which is systemic).
3. Henoch-Schönlein purpura (systemic presentation: kidneys
+ joints + vessels).
4. Hereditary nephritis or Alport syndrome ( most develop RF
around the age of 20)
5. Benign familial hematuria (presents with microscopic
hematuria)
6. Membranoproliferative glomerulonephritis
7. Lupus nephritis
HEMATURIA
Differential diagnosis of RBC cast
glomerulonephritis with low C3:
• Acute post-streptococcal (infectious)
glomerulonephritis comprises 80%.
• Lupus nephritis (SLE), in children 80% have a
renal presentation unlike adults.
• Membrane proliferative glomerulonephritis.
• A child presenting with generalized edema
(including peri-orbital and scrotal edema),
hypertension, oligouria and gross hematuria is
seen in any glomerulonephritis, most
commonly acute post infectious.
• Minimal change: no hematuria.
HEMATURIA
Postinfectious GN:
• Begins 7-21 days after group A beta-hemolytic
streptococcal infection.
• Antibiotic treatment for the infections will not
prevent the nephritis (hypertension, oliguria, edema,
and high creatinine).
• Present with tea colored urine, edema and
hypertension.
• May present with only microscopic hematuria, and
the presence of edema is serious.
HEMATURIA
Postinfectious GN (cont.)
• ASO may be negative early in the course, but is positive
in 1-2 weeks.
• C3 low in 90% of patients for 6 weeks caused by
complement activation (alternative pathway) and its
consumption.
• C4 normal
• After recovery, gross hematuria might disappear but
microscopic hematuria my persist for 2 years, but the
edema resolves.
• glomerulonephritis has a good prognosis, 95% of the
cases resolve.
HEMATURIA
IgA nephropathy:
• The most common chronic GN in Europe and Asia.
• The most common cause of hematuria in children
• 15% of children with Prolonged hematuria (> 1 year)
will have IgA nephropathy
• Present with gross hematuria during viral illness
usually presents 1 day after the common cold.
• Very serious condition almost 40% will end in renal
failure and even with transplant most are rejected
and there is also an increased risk of recurrence.
HEMATURIA
IgA nephropathy (cont.)
• Microscopic hematuria present between episodes of gross
hematuria.
• Recurrent disease unlike post infectious it happens only
once because of immunity.
• There is no laboratory test diagnostic of GN. Recurrent
hematouria is suggestive.
• Its a clinical Diagnosis confirmed by histopathologic
demonstration of mesangial deposition of IgA
• 25% of children with IgA nephropathy will progress to
chronic renal insufficiency.
• Poor outcome: cresentic GN, older age group,
hypertension, nephrotic range proteinuria.
HEMATURIA
Which patients will progress to ESRD:
1.Age above 8.
2.Male.
3.Heavy (nephrotic range) proteinuria in
addition to hematuria.
4.Hypertension.
5.Needs aggressive management.
HEMATURIA
Alport hereditary nephritis:
• Episodes of recurrent or persistent micro and macroscopic
hematuria.
• X-linked dominant disease resulting in a defect in collagen
IV synthesis, and the basement membrane is disruptedthick..
• Organs affected are kidney (Glomerulonephritis, ESRD),
ears (deafness), eyes.
• They develop renal failure early in life, usually in 2nd to 3rd
decade.
• Family History: Family history of deafness especially in
females. Male individuals with nerve deafness and
progression to ESRD. Females usually have a milder form of
the disease, and don’t progress to RF.
HEMATURIA
Alport hereditary nephritis (cont.)
• The diagnosis is confirmed by renal biopsy.
• Hearing test should be done regularly to prevent
speech or educational handicap, and family members
should be screened for hearing problems.
• Patients must be transferred to special schools for
hearing loss and renal failure.
• Good-pasture diseases post transplant (small risk).
• Female may have a hearing deficit without any urinary
abnormalities.
HEMATURIA
Benign Familial Hematuria:
• Thin glomerular basement membrane nephropathy unlike thick
BM in alport.
• Occurs in at least 1% of the population.
• Inherited as AD or AR manner.
• Absence of proteinuria (its presence excludes benign familial
hematuria), renal failure, hearing deficits, or ophthalmologic
abnormalities.
• Persistent Microscopic hematuria (unlike alport recurrent),
dysmorphic RBC’s.
• Rarely progress to renal failure vs. alport which develops it.
• It’s a diagnosis of exclusion and if the patient has a family history
of hematuria then it’s alport.
HEMATURIA
Rapidly Progressive GN:
• It is not a disease itself, but it’s the result of any renal
disease within 2-5 weeks.
• Presents with symptoms and signs similar to APIGN,
but continuous rising in renal proteins. In APIGN the
proteinuria will go back within 1 week.
• Require the urgent attention of a Pediatric
Nephrologist.
• Laboratory Studies show ARF
• Untreated RPGN can result in ESRD in a few weeks.
• Normal patient who develops seizures due to uremia
and severe hypertension.
• Renal biopsy is mandatory to assess the
percentage of dead tissue and is done
immediately and demonstrates glomerular
crescent (dead tissue).
– If > 50% dead tissue, transplant is required.
– If < 50% can give them immune-suppressant
therapy and steriods.
HEMATURIA
Causes of non-Glomerular hematuria in
order of its incidence in SA
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Hypercalciuria
Infections (bacterial or viral)
Papillary necrosis (HbS)
Urolithiasis
Trauma
Foreign body
Exercise-induced hematuria
HEMATURIA
Hypercalciuria:
• Increased urinary excretion of Ca despite normal s.
Ca
• Present in 5% of healthy children
• Most frequent cause of isolated hematuria in nonglomerular hematuria patients.
HEMATURIA
Idiopathic Hypercalciuria:
• Renal hypercalciuria: result from a tubular leak of
calcium.
• Absorptive hypercalciuria : results from increased
gastrointestinal absorption of calcium.
HEMATURIA
Idiopathic Hypercalciuria:
• There is often a family history of renal stones.
• Symptoms include dysuria, suprapubic pain, renal
colic.
HEMATURIA
Idiopathic Hypercalciuria:
• Present with microscopic hematuria and episodic
gross hematuria.
• Urine RBC’s are shaped normally with no cast.
• The mechanism of the hematuria involve
irritations to the renal tubules by ca-containing
crystals.
• High risk of development of renal stones.
HEMATURIA
Idiopathic Hypercalciuria:
• Screening for hypercalciuria: spot urinary ca/
creatinine ratio.
• A ration of > 0.21 is indicative of hypercalciuria. Ratio
of urinary calcium to creatinine from an early
morning sample.
• Confirmation of hypercalciuria by collecting a timed
(either 12 or 24 hours) urine for ca excretion.
• An excretory rate of greater than 4 mg/kg/day is
abnormal.
HEMATURIA
Idiopathic Hypercalciuria treatment:
• Increase fluid intake to dilute the urine and improve
hypertension.
• Severe ca restriction should be avoided because they
are growing children.
• Hydrochlorothiazide (HCT) decrease urinary ca
excretion but should not be given routinely unless
there is a family history of stones.
• HCT in a child with isolated hematuria with no
previous nephrolithiasis is not recommended.
HEMATURIA
History clues:
• Duration and pattern of hematuria
• Family history (hematuria, renal failure, deafness,
urolithiasis)
• Pharyngitis, URTI
• Dysuria or other symptoms of urinary infections
• Rash (HSP)
• Abdominal pain (infections, stone, HSP)
• Drugs (anticoagulant)
HEMATURIA
Physical examinations clues:
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Hypertension always mandatory, edema, pallor
Rash, impetigo
Abdnominal or flank tenderness (infection)
Abdominal mass (tumors) such as Wilm’s tumor.
Child abuse
Ecchymoses, petechiae, hemangiomas
Evidence of abdominal trauma
External genitalia for trauma or bleeding to rule out foreign body.
Growth pattern because early presentation of RF is failure to thrive.
Hearing test
HEMATURIA
Basic Laboratory Evaluation:
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Urine culture
CBC for anemia
Serum creatinine for kidney function
Aso titre for APIGN
Urine ca: creatinine ratio
Urine protein: creatinine ratio for severe
proteinuria.
• C3 levels to r/o lupus, membrane proliferative, or
APIGN.
HEMATURIA
• Renal ultrasonography for size, solitary kidney,
stones (nephrocalcinosis), cysts, and tumors
– If no clear cause, screen 1st degree relatives urine
test with dipstick.
– If still no clear cause, refer to the Pediatric
Nephrologist initially for immune studies rather
than to the Pediatric Urologist.
HEMATURIA
Other evaluation procedures:
• Renal biopsy
• Cystoscopy
• Renal angiography (rarely indicated)
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