1. Approach to a child with
Hematuria :
Sunil Agrawal
1st year
MD Pediatrics, IOM

2. Contents:
• Introduction
• Pathophysiology
• Causes
• History
• Examination
• Investigations
• Management

3. 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

4. • 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

5. Causes of Hematuria:
A) Glomerular hematuria
Isolated renal disease Multisystem disease
-Postinfectious GN (Post streptococcal) -HSP nephritis
- IgA nephropathy( Berger ds) -SLE nephritis
- Alport syndrome( hereditary ) -HUS
- Thin Glomerular Basement membrane -Wegener granulomatosis
disease -Polyarteritis nodosa
- Membranoproliferative GN
-Goodpasture syndrome
- Membranous nephropathy
-HIV nephropathy
- Focal segmental glomerulosclerosis
- Antiglomerular basement membrane -Sickle cell glomerulopathy
ds

6. B) Extraglomerular hematuria
Upper Urinary tract
Tubulointerstitial
Pyelonephritis
Interstitial nephritis
ATN
Papillary necrosis
Nephrocalcinosis
Anatomic
Hydronephrosis
Polycystic kidney disease
Tumor (Wilms,
Rhabdomyosarcoma,
Angiomyolipoma)
Trauma

7. Vascular:
• Arterial/venous thrombosis
• Malformation (aneurysms, hemangioma)
• Nutcracker syndrome
• Hemoglobinopathy (Sickle cell trait/disease)
Crystalluria: Calcium, Oxalate, Uric acid
Medications: NSAIDs, anticoagulants

8. Lower urinary tract
Inflammation- infectious and
non infectious
Cystitis
Urethritis
Urolithiasis
Trauma
Coagulopathy
Heavy exercise
Bladder tumor
Factitious syndrome / by proxy

9. Common causes of gross hematuria:
• Urinary tract infection
• Meatal stenosis
• Perineal irritation
• Trauma
• Urolithiasis/hypercalciuria
• Coagulopathy
• Tumor

10. Glomerular cause of gross hematuria
IgA nephropathy
Alport syndrome
Thin glomerular basement membrane disease
Post infectious glomerulonephritis
HSP nephritis
SLE nephritis

11. 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)

12. 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

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

14. 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

15. 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, Wilm’s
tumour
• Joint pain (HSP, SLE)
• Rashes (HSP, SLE, PAN)
• Neurologic – SLE, HUS (seizures, irritability)
• Jaundice: Hemolysis, Obstructive jaundice

16. • 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)

17. • 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

18. 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

19. • 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 (Wilms)
• Hearing assessment: Alport (B/L SNHL)

20. General Approach to
Investigate the child with
Hematuria

21. 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

22. Investigations:
Urine microscopy: Presence of RBCs and casts (> 5
RBCs per HPF) in centrifuged urine
Glomerular Non - glomerular
1. Brown, cola coloured or smoky 1. Bright red, pink
2. RBC casts 2.Terminal hematuria/
Passage of clots
3. Proteinuria 2+ or more 3. Proteinuria of < 2+
4. Deformed urinary RBCs 4. Normal morphology of RBCs

23. 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.

24. • With respect to the albumin-to-total-protein 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.

25. 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

26. Urine albumin-to-total-protein ratio sensitivities and specifi ities
in differentiating glomerular and nonglomerular hematuria. At a
ratio of 0.59, sensitivity and specificity were 96.2% and 100%,
respectively.

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

28. 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
– Spot urine calcium-creatinine ratio >0.21

29. 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
– Chest X-Ray (Pulmonary oedema, CHF)

30. 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

31. Dx Histology Clinical Lab
IgA IgA deposition in the Gross, No specific
Nephro- mesangium, glomerular intermittent, changes,
pathy sclerosis, proliferative changes, painless although
crescents in severe cases hematuria increased serum
IgA levels
observed in some
patients
HSP Same as IgA nephropathy Purpura, joint No specific
pains, laboratory data
abdominal
pain,
hematuria, etc
SLE Mild glomerulitis, proliferative Hematuria, Abnormal C3, C4,
changes, immune complex proteinuria, ANA, dsDNA,
deposition, crescents, hypertension, anemia,
immunoglobulin deposition joint pains, thrombocytopeni
rashes, etc a, etc

32. Dx Histology Clinical Lab
Alport Some thinning of basement Sensorineural No
Syndrome membranes, "basket weave" hearing loss, corneal specific
changes in the glomerular abnormalities, changes
basement hematuria, renal
membrane on electron failure
microscopy
Thin Average glomerular basement Persistent No
Basement membranes thin (reported to microscopic or gross specific
Membrane be 100-200 nm) hematuria, changes
disease significant family
history
Mesangio- Glomerular lobulations, Hematuria, C3 levels
proliferative thickening of the mesangial proteinuria, may be
GN matrix and glomerular hypertension low
basement membranes,
crescents, etc

33. 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

34. Summary

38. For Asymptomatic, isolated
microscopic hematuria:
Isolated microscopic
hematuria
Repeat urinalysis weekly x 2 Negative F/U Urine R/M with
(No exercise x 48hrs) examination
Persistent hematuria
Test parents for Positive Benign Familial
hematuria Hematuria
No Yes
Family h/o calculi Urine Ca/Cr ratio
No Normal
+Hearing test, +USG, Yearly Urine R/M,
+X-Ray KUB examination, BP

39. 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)

40. 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

41. References:
• Nelson Textbook of Pediatrics, 19th Ed
• Nelson Essentials of Pediatrics, 6th 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