Approach to a child with

Hematuria :

Sunil Agrawal
1st year
MD Pediatrics, IOM

Contents:

Introduction
Pathophysiology
Causes
History
Examination
Investigations
Management

Introduction
Hematuria means blood in urine.
It may be Gross or macroscopic and
microscopic hematuria
Gross hematuria is seen by naked
eyes while microscopic hematuria
needs microscope. Hematuria is
defined as the presence of at least 5
red blood cells per HPF of centrifuged
urine and/or 5 RBC per microliter in
uncentrifuged specimen

 Pathophysiology:
Structural disruption in the integrity of
glomerular basement membrane caused by
inflammatory or immunologic processes
Toxic disruptions of the renal tubules
Mechanical erosion of mucosal surfaces in
the genitourinary tract

Causes of Hematuria:
A) Glomerular hematuria
Isolated renal disease
-Postinfectious GN (Post

streptococcal)
- IgA nephropathy( Berger ds)
- Alport syndrome( hereditary )
- Thin Glomerular Basement
membrane disease
- Membranoproliferative GN
- Membranous nephropathy
- Focal segmental
glomerulosclerosis
- Antiglomerular basement

Multisystem disease
-HSP nephritis
-SLE nephritis
-HUS
-Wegener granulomatosis
-Polyarteritis nodosa
-Goodpasture syndrome
-HIV nephropathy
-Sickle cell
glomerulopathy

B) Extraglomerular hematuria
Upper Urinary
tract

Tubulointerstitial
Pyelonephritis
Interstitial nephritis
ATN
Papillary necrosis
Nephrocalcinosis
Anatomic
Hydronephrosis
Polycystic kidney
disease
Tumor (Wilms,
Rhabdomyosarcoma
, Angiomyolipoma)
Trauma

Vascular:

Arterial/venous thrombosis

Malformation (aneurysms, hemangioma)

Nutcracker syndrome

Hemoglobinopathy (Sickle cell

trait/disease)
Crystalluria: Calcium, Oxalate, Uric acid
Medications: NSAIDs, anticoagulants

Lower urinary tract

Inflammation- infectious
and non infectious
Cystitis
Urethritis
Urolithiasis
Trauma
Coagulopathy
Heavy exercise
Bladder tumor
Factitious syndrome / by
proxy

Common causes of gross

hematuria:
Urinary tract infection
Meatal stenosis
Perineal irritation
Trauma
Urolithiasis/hypercalciu
ria
Coagulopathy
Tumor

Glomerular cause of gross hematuria

IgA nephropathy
Alport syndrome
Thin glomerular basement membrane
disease
Post infectious glomerulonephritis
HSP nephritis
SLE nephritis

Causes of Hematuria in the Newborn:

Renal vein thrombosis (Asphyxia, dehydration,
shock)
Renal artery thrombosis
Autosomal recessive polycystic kidney disease
Obstructive uropathy
Urinary tract infection
Bleeding and clotting disorders
Trauma, bladder catheterization
Cortical necrosis (Hypoxic/ischemic perinatal
insult)
Nephrocalcinosis (Frusemide in premature)

History:
Age:

2-5yrs: Wilms tumor

5-12yrs: PSGN

Sex: F>>M in >1-2yrs: UTI

F>>M: SLE nephritis
M>F : X-linked form of Alport syndrome

Race: whites: Idiopathic hypercalciuria

blacks: Sickle cell disease

Colour of urine:
Colour

Causes

Dark yellow

Normal concentrated urine

Dark brown or Bile pigments

black
Homogentisic acid, melanin,
tyrosinosis, methemoglobinuria
Cola coloured Glomerular hematuria
Red or pink
urine

Extraglomerular hematuria,
Hemoglobin, Myoglobin,
Porphyrins, Chloroquine,
Deferoxamine, Beets, blackberries,
Rifampin, Red dyes in food, Urates

Characteristics of urine:
Amount of urine: Reduced in AGN, ARF
Clots in urine: Extraglomerular
Frequency, Dysuria, recent enuresis
: UTI
Frothy urine: Suggests Proteinuria seen
in Glomerular diseases
Timing: Initial stream from urethra
(Urethrorrhagia spotting in underwear);
Terminal (with suprapubic pain,
disturbance of micturition) from bladder

Associated Symptoms:
Fever: Infections, SLE, AGN
Facial puffiness, Oedema of legs, weight
gain, Shortness of breath: Acute
Glomerulonephritis
Hypertension (Headache, visual
changes, epistaxis, seizures): AGN, ARF
Abdominal pain: Urolithiasis (Loin to
groin), UTI, clots, Nutcracker syndrome
Painless: Glomerular
Abdominal mass: Hydronephrosis, PKD,
Wilms tumour
Joint pain (HSP, SLE)
Rashes (HSP, SLE, PAN)
Neurologic SLE, HUS (seizures,
irritability)

 H/o exercise, menstruation, recent bladder

catheterization or passage of a calculus
Recent upper respiratory (1-2wks
back), skin infection (3-6 wks): PSGN
GI infection: HUS, HSP nephritis
Gross hematuria precipitated by URI:
Alport syndrome, IgA Nephropathy
H/o bleeding from other sites: Bleeding
disorders, Hemoptysis in Good Pasture
syndrome
H/o Trauma, abdominal surgery, Child
abuse (Social factors - Munchausen), crush
injury
H/o ingestion of drugs (ATT
Rifampicin, Ibuprofen, Chloroquine,
Metronidazole, Iron), i.v. contrast agents
(Toxic nephropathy, RVT)

 H/o Vision or hearing defects: Alport

syndrome
Family h/o: Hereditary glomerular
diseases (Alport syndrome, Thin
glomerular Basement Membrane
Disease, IgA Nephropathy),
Urolithiasis, Hypercalciuria, Sickle
cell disease/trait
H/o consanguinity or affected siblings
in ARPKD, Metabolic disorders

Examination:
Vitals:
BP: in AGN, PKD
Temperature
Oedema: in AGN
Pallor: Bleeding disorders, HUS, SLE, CRF
JVP: Raised in CHF
Per abdomen: Mass
Kidney: Hydronephrosis (Urinary tract
obstruction), Wilms tumour; B/L in
ARPKD, hydronephrosis
Bladder palpable: Distal obstruction
Tenderness: HSP

 Skin lesions
Purpura(HSP)
Butterfly rash (SLE)
Bruises (Trauma, Child abuse)
Abnormal external genitalia e.g.
ambiguous genitalia in WAGR syndrome
(Wilms, aniridia, genital anomalies, mental
retardation), Wilms tumour hypospadias,
cryptorchidism, Genital trauma
Signs of Congestive cardiac failure,
HTNsive encephalopathy: AGN
Joint swelling, tenderness: HSP, SLE
Ophthalmologic: Alport syndrome
(Anterior lenticonus, macular flecks,
recurrent corneal erosions), Aniridia

General Approach to
Investigate the child with
Hematuria

Investigations:
Urine dipstick test:
Based on the peroxidase-like
activity of hemoglobin
It can detect trace
amounts of hemoglobin
and myoglobin.
Can detect 5-10 intact
RBC per mm3 of unspun
urine
False +ve: Urine pH >9,
H2O2
False ve: High ascorbic
acid, formalin
Also for urine albumin

Investigations:
Urine microscopy: Presence of RBCs and casts (>
5 RBCs per HPF) in centrifuged urine
Glomerular
1. Brown, cola coloured or smoky
2. RBC casts
3. Proteinuria 2+ or more
4. Deformed urinary RBCs

Non - glomerular
1. Bright red, pink
2.Terminal hematuria/
Passage of clots
3. Proteinuria of < 2+
4. Normal morphology of RBCs

Study on Evaluation of hematuria using the

urinary albumin-to-total-protein ratio to
differentiate glomerular and nonglomerular
bleeding
N. Ohisa R. Matsuki H. Suzuki H. Miura Y. Ohisa K. Yoshida
Department of Clinical Laboratory, Tohoku University Hospital,
Sendai, Japan
microscopy-based differentiation is not only tedious but the sensitivity and
specificity may vary from one examiner to another. Furthermore, once
the specimen has been frozen, differentiation becomes difficult.
A total of 143 random urine specimens from patients seen at the Division of
Nephrology, Endocrinology and Vascular Disease and the Urology Department
at Tohoku University Hospital were included in the study. The inclusion criterion
for the study was a diagnosis of glomerular disease based on clinical features
or histopathology with hematuria (5 or more RBCs per high-power fi eld). Of the
104 patients diagnosed with glomerular disease and 39 specimens from
patients with nonglomerular disease, used as controls in the study.

 With respect to the albumin-to-totalprotein ratio, the mean value in the

glomerular disease group was 0.72 }
0.10, whereas the mean in the
nonglomerular disease group was 0.35 }
0.17 (P < 0.001). The distribution of the
albumin-to-total-protein ratio in the
glomerular and nonglomerular disease
groups was clearly differentiated.
Sensitivity and specificity as a function of
the albumin-to-total-protein ratio. At a
ratio cutoff of 0.59, sensitivity and
specificity was maximized at 96.2% and
100%, respectively.

Distribution of urinary albumin-to-total-protein ratio in glomerular

and nonglomerular hematuria. The mean albumin-to-totalprotein
ratio in the glomerular disease group was signifi cantly higher than
that in the nonglomerular disease group. A cutoff of 0.59 excluded
all nonglomerular disease cases, while detecting all but three
glomerular disease cases. Gl, glomerular disease; non-Gl,
nonglomerular disease; vertical axis, albumin-to-total-protein ratio;
horizontal axis, glomerular disease, nonglomerular disease

Urine albumin-to-total-protein ratio sensitivities and

specifi ities
in
differentiating
glomerular
and
nonglomerular
hematuria. At a

Cola/ brown urine?

Proteinuria(>30mg/dl)?
RBC cast?
Acute nephritic syndrome?
NO
Yes
Extraglomerular hematuria
Glomerular hematuria
Step 1
CBC
Urine culture
Electrolytes,Ca
Step 2
BUN/Cr
Serum protein/albumin Urine Ca/Cr
Renal/ bladder USG
Cholesterol
Step 3
C3/C4
Urinalysis: siblings, parents
ASO/Anti-DNase B
Serum electrolytes, Cr, Ca
ANA
Antineutrophil antibody If crystalluria, urolitiasis or
nephrocalcinosis:
Throat/ skin culture
24-hr urine for Ca, Cr, Uric acid,
24-hour urine total protein
oxalate
creatinine clearance
If hydronephrosis/pyelocaliectasis:

Investigations:
Urine C/S
RFT: Blood urea nitrogen/serum creatinine, Na/K
(Na in AGN, K in ARF)
Complete blood counts (CBC): Hb - in
bleeding, HUS, SLE, CRF; Abnormal TC, DC in
infections, HUS, in SLE;
Platelet counts and Coagulation studies:
(history suggestive of bleeding disorder, HUS),
Sickle cell (Hemoglobin electrophoresis)
PBS: Microangiopathic hemolytic anemia
ESR, CRP - Infections
24 hr urinary protein, Spot urinary protein:
Creatinine ratio, Serum albumin and cholesterol if
associated proteinuria (Nephrotic syndrome)
Urine calcium: Hypercalciuria is a relatively
common finding in children.
24-hour urinary calcium (>4 mg/kg/d), or

Investigations:
Imaging Studies
Renal and bladder sonography: Urinary
tract anomalies, such as hydronephrosis,
hydroureter, nephrocalcinosis, tumor, and
urolithiasis, Renal parenchymal disease
X-Ray KUB: calculi
Doppler study of renal vessels and IVC:
Renal vein thrombosis
Intravenous urography
Spiral CT scan - Urolithiasis, Wilms tumor and
polycystic kidney disease, Renal trauma
Micturating cystourethrograms - Urethral
and bladder abnormalities (eg, cystitis), in
recurrent UTI to r/o VUR, anomalies
Radionuclide studies Renal function and
perfusion
Angiogram

Investigations:
Renal biopsy:
Relative indications Significant proteinuria (3+ or more) or nephrotic
syndrome +
Recurrent persistent hematuria (Microscopic
>2yrs)
Abnormal renal function, Persistent HTN
Hematuria, Proteinuria, diminished renal function,
low C3 level persist beyond 2 mo of onset of AGN
Absence of evidence of streptococcal infection
Serologic abnormalities (abnormal ANA or dsDNA
levels)
A family history of end stage renal disease or
evidence of Chronic renal disease in patient

Dx

Histology

Clinical

Lab

IgA
Nephropathy

IgA deposition in the

mesangium, glomerular
sclerosis, proliferative
changes, crescents in
severe cases

Gross,
intermittent
, painless
hematuria

No specific
changes,
although
increased
serum
IgA levels
observed in
some patients

HSP

Same as IgA nephropathy

Purpura,
joint pains,
abdominal
pain,
hematuria,
etc

No specific
laboratory
data

SLE

Mild glomerulitis,
proliferative changes,
immune complex
deposition, crescents,
immunoglobulin
deposition

Hematuria,
proteinuria,
hypertensio
n, joint
pains,
rashes, etc

Abnormal C3,
C4, ANA,
dsDNA,
anemia,
thrombocytop
enia, etc

Dx

Histology

Clinical

Lab

Alport
Syndrom
e

Some thinning of
basement membranes,
"basket weave" changes
in the glomerular
basement
membrane on electron
microscopy

Sensorineural
No
hearing loss,
specific
corneal
changes
abnormalities,
hematuria, renal
failure

Thin
Basemen
t
Membran
e disease

Average glomerular
basement membranes
thin (reported to be 100200 nm)

Persistent
No
microscopic or
specific
gross hematuria, changes
significant family
history

Mesangio
proliferat
ive GN

Glomerular lobulations,
thickening of the
mesangial matrix and
glomerular basement
membranes, crescents,
etc

Hematuria,
proteinuria,
hypertension

C3
levels
may be
low

Investigations:
Cystourethroscopy: Terminal
hematuria, disturbances of
micturition, suprapubic pain (Only if
strong suspicion of bladder
ulceration, tumours)
Screening of first degree relatives in
persistent hematuria

Summary

For Asymptomatic, isolated microscopic

hematuria:
Isolated microscopic
hematuria
Repeat urinalysis weekly x 2
(No exercise x 48hrs)

Negative

F/U Urine R/M with

examination

Persistent hematuria
Test parents for
hematuria
No
Family h/o calculi
No
+Hearing test, +USG,
+X-Ray KUB

Positive
Yes
Normal

Benign Familial
Hematuria
Urine Ca/Cr ratio
Yearly Urine R/M,
examination, BP

Management:
According to cause:
Reassurance and F/U
Treat cystitis, pyelonephritis, AGN: Antibiotics
Supportive treatment: Diuretics, Fluid and salt
restriction, Antihypertensives
Monitoring BP, I/O, weight, Urine R/M
Treat Hyperkalemia, ARF, CHF, acidosis, fluid
overload, HTN and its complications
ACE inhibitors useful in proteinuria
Immunosuppressive therapy: Depending on cause
(Steroids, cyclophosphamide)

Management:
Idiopathic Hypercalciuria:
Hydrochlorothiazide, Potassium citrate, Sodium
restriction
Calculi: Plenty of water
ESRD: Dialysis, Renal transplantation
Correct thrombocytopenia, anemia,
coagulation factor deficiency
Renal vein thrombosis: Anticoagulant
therapy or thrombectomy may be needed
Surgical correction: Calculi, PUJ obstruction,
Posterior urethral valves, Wilms tumour

References:
Nelson Textbook of Pediatrics, 19th Ed
Nelson Essentials of Pediatrics, 6 th Ed
O.P. Ghai Essential pediatrics, 7th Ed
Pediatric Nephrology, Shrivastava, Bagga,
4th Ed
Japanese Society of Nephrology 2007
Indian J Pediatrics 1999; 66 : 207-214
Various Websites

THA

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O
Y
NK