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 Multisystem disease

-Postinfectious GN (Post streptococcal) -HSP nephritis

- IgA nephropathy( Berger ds)
- Alport syndrome( hereditary )
- Thin Glomerular Basement membrane
disease
- Membranoproliferative GN
- Membranous nephropathy
- Focal segmental glomerulosclerosis
- Antiglomerular basement membrane
ds
-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/hypercalciuria
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 Extraglomerular hematuria,
urine 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)
Jaundice: Hemolysis, Obstructive jaundice
 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 (Wilms)
Hearing assessment: Alport (B/L SNHL)
 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 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
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-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.
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
ratio of 0.59, sensitivity and specificity were 96.2% and 100%,
respectively.
 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
 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
 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)
 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 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
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
 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 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
 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, 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