Evaluation and Approach to Hematuria in Children
Introduction
Hematuria, defined as the presence of blood or red blood cells (RBCs) in the urine, is a common finding in pediatric practice. It can be either gross (visible to the naked eye) or microscopic (detected only on urinalysis). The prevalence of microscopic hematuria in children ranges from 0.5-2% in routine screenings, while gross hematuria is less common but often more alarming to patients and families.
Hematuria can be a sign of various underlying conditions, ranging from benign and transient causes to serious renal or urological disorders. Therefore, a systematic approach to evaluation is crucial for pediatricians to ensure appropriate management and timely referral when necessary.
Etiology
Causes of hematuria and red urine in children:
Upper Urinary Tract Disease
Isolated Renal Disease
- Immunoglobulin (Ig) A nephropathy (Berger disease)
- Alport syndrome (hereditary nephritis)
- Thin glomerular basement membrane nephropathy
- Postinfectious GN (poststreptococcal GN)
- Membranous nephropathy
- Membranoproliferative GN
- Rapidly progressive GN
- Focal segmental glomerulosclerosis
- Anti–glomerular basement membrane disease
- Hereditary angiopathy with nephropathy, aneurysms, muscle cramps (HANAC)
Multisystem Disease
- Systemic lupus erythematosus nephritis
- Henoch-Schönlein purpura nephritis
- Granulomatosis with polyangiitis (formerly Wegener granulomatosis)
- Polyarteritis nodosa
- Goodpasture syndrome
- Hemolytic-uremic syndrome
- Sickle cell glomerulopathy
- HIV nephropathy
Tubulointerstitial Disease
- Pyelonephritis
- Interstitial nephritis
- Papillary necrosis
- Acute tubular necrosis
Vascular Disorders
- Arterial or venous thrombosis
- Malformations (aneurysms, hemangiomas)
- Nutcracker syndrome
- Hemoglobinopathy (sickle cell trait/disease)
- Crystalluria
Anatomic Disorders
- Hydronephrosis
- Cystic-syndromic kidney disease
- Polycystic kidney disease
- Multicystic dysplasia
- Tumor (Wilms tumor, rhabdomyosarcoma, angiomyolipoma, medullary carcinoma)
- Trauma
Lower Urinary Tract Disease
- Inflammation (infectious and noninfectious)
- Cystitis
- Urethritis
- Urolithiasis
- Trauma
- Coagulopathy
- Heavy exercise
- Bladder tumor
- Factitious syndrome, factitious syndrome by proxy
Common Causes of Gross Hematuria
- Urinary tract infection
- Meatal stenosis with ulcer
- Perineal irritation
- Trauma
- Urolithiasis
- Hypercalciuria
- Obstruction
- Coagulopathy
- Tumor
- Glomerular disease
- Postinfectious glomerulonephritis
- Henoch-Schönlein purpura nephritis
- IgA nephropathy
- Alport syndrome (hereditary nephritis)
- Thin glomerular basement membrane disease
- Systemic lupus erythematosus nephritis
Other Causes of Red Urine
Heme Positive
- Hemoglobin
- Myoglobin
Heme Negative
Drugs
- Adriamycin
- Chloroquine
- Deferoxamine
- Hydroxycobalamin
- Ibuprofen
- Iron sorbitol
- Levodopa
- Metronidazole
- Nitrofurantoin
- Phenazopyridine (Pyridium)
- Phenolphthalein
- Phenothiazines
- Phenytoin
- Quinine
- Rifampin
- Salicylates
- Sulfasalazine
Dyes (Vegetable/Fruit)
- Beets
- Blackberries
- Blueberries
- Food and candy coloring
- Paprika
- Rhubarb
Metabolites
- Homogentisic acid
- Melanin
- Methemoglobin
- Porphyrin
- Tyrosinosis
- Urates
Clinical Presentation
The presentation of hematuria can vary depending on the underlying cause and whether it is gross or microscopic. Key aspects of the clinical presentation include:
Gross Hematuria
- Visible blood in urine, ranging from pink to red to cola-colored
- May be accompanied by clots
- Often intermittent
- Can be associated with dysuria, flank pain, or abdominal pain
Microscopic Hematuria
- Typically asymptomatic and discovered incidentally
- Defined as >5 RBCs per high-power field on microscopic examination of centrifuged urine
- May be transient or persistent
Diagnostic Approach
History
A thorough history is crucial in evaluating hematuria. Key elements to consider include:
- Timing and duration of hematuria
- Associated symptoms (e.g., dysuria, flank pain, edema, rash)
- Recent illnesses, particularly streptococcal infections
- Family history of renal disease, hearing loss, or hematuria
- Medication use, including over-the-counter drugs
- Recent trauma or vigorous exercise
- Dietary history (e.g., excessive salt intake, foods that can discolor urine)
Physical Examination
A comprehensive physical examination should include:
- Blood pressure measurement
- Assessment for edema
- Abdominal examination for masses or tenderness
- Skin examination for rashes or purpura
- Genital examination to rule out local causes of bleeding
- Evaluation of growth and development
Laboratory Investigations
Urinalysis
Urinalysis is the cornerstone of hematuria evaluation. Key components include:
- Dipstick testing: Provides a rapid screen for hematuria, proteinuria, and other urinary abnormalities
- Microscopic examination: Confirms the presence of RBCs and assesses for RBC casts, which suggest glomerular origin
- Urine protein-to-creatinine ratio: Quantifies proteinuria
Additional Tests
- Complete blood count (CBC)
- Serum creatinine and electrolytes
- Complement levels (C3, C4)
- Antistreptolysin O (ASO) titer
- Antinuclear antibody (ANA)
- Coagulation studies (PT, PTT)
- Urine calcium-to-creatinine ratio
- Urine culture if UTI is suspected
Imaging Studies
Imaging studies may be necessary depending on the clinical presentation and initial laboratory findings:
- Renal ultrasound: First-line imaging modality to evaluate renal structure, size, and for the presence of stones or masses
- Voiding cystourethrogram (VCUG): Indicated if vesicoureteral reflux is suspected
- CT scan or MRI: May be necessary for further evaluation of masses or complex renal anatomy
Renal Biopsy
Renal biopsy may be considered in cases of persistent hematuria with proteinuria, renal insufficiency, or other concerning features suggestive of glomerular disease. The decision to perform a biopsy should be made in consultation with a pediatric nephrologist.
Differential Diagnosis
The differential diagnosis of hematuria in children is broad and depends on various factors, including age, associated symptoms, and laboratory findings. Some key considerations include:
Isolated Hematuria
- Hypercalciuria
- Nutcracker syndrome
- Thin basement membrane nephropathy
- IgA nephropathy
- Alport syndrome (early stages)
Hematuria with Proteinuria
- Post-streptococcal glomerulonephritis
- IgA nephropathy
- Alport syndrome
- Lupus nephritis
- Membranoproliferative glomerulonephritis
Hematuria with Dysuria or Frequency
- Urinary tract infection
- Hemorrhagic cystitis
- Bladder stones
Hematuria with Abdominal or Flank Pain
- Nephrolithiasis
- Ureteropelvic junction obstruction
- Renal trauma
- Renal vein thrombosis
Management Approach
The management of hematuria in children depends on the underlying cause and severity of the condition. A stepwise approach is recommended:
Initial Management
- Confirm the presence of true hematuria and rule out pseudohematuria (e.g., from foods, medications)
- Assess for associated symptoms and signs of systemic illness
- Perform initial laboratory tests, including urinalysis, urine culture, and serum creatinine
- Manage any acute conditions (e.g., UTI, nephrolithiasis) appropriately
Further Evaluation
- If hematuria persists, proceed with additional laboratory tests as outlined above
- Consider renal ultrasound for structural evaluation
- Assess for family history and consider genetic testing if hereditary nephritis is suspected
- Monitor blood pressure and renal function
Referral to Pediatric Nephrology
Consider referral to a pediatric nephrologist in the following situations:
- Persistent gross hematuria
- Persistent microscopic hematuria with proteinuria
- Hematuria associated with hypertension or renal insufficiency
- Family history of hereditary nephritis
- Abnormal renal ultrasound findings
- Recurrent episodes of gross hematuria
Long-term Monitoring
For children with persistent hematuria without a clear etiology:
- Perform urinalysis and blood pressure check every 3-6 months
- Monitor renal function annually
- Reassess the need for further investigations or referral based on clinical course
Patient Education
Educating patients and families is crucial in the management of hematuria. Key points to address include:
- Explanation of the difference between benign causes and those requiring further evaluation
- Importance of follow-up and adherence to monitoring plans
- Signs and symptoms that should prompt immediate medical attention
- Dietary and lifestyle modifications, if applicable
- Genetic implications and screening recommendations for family members in cases of hereditary conditions
Special Considerations
Exercise-induced Hematuria
Exercise-induced hematuria is relatively common in children and typically benign. Management includes:
- Confirming the temporal relationship with exercise
- Ensuring adequate hydration before, during, and after exercise
- Monitoring for resolution within 24-48 hours post-exercise
- Further evaluation if hematuria persists beyond this period
Nutcracker Syndrome
Nutcracker syndrome, caused by compression of the left renal vein between the aorta and superior mesenteric artery, can present with hematuria. Considerations include:
- Suspicion in cases of recurrent left-sided gross hematuria
- Diagnosis typically confirmed by Doppler ultrasound or CT angiography
- Management often conservative, with surgery reserved for severe cases
Hypercalciuria
Hypercalciuria is a common cause of isolated hematuria in children. Management includes:
- Confirmation with 24-hour urine calcium collection or spot urine calcium-to-creatinine ratio
- Dietary modifications (increased fluid intake, moderate sodium restriction)
- Consideration of thiazide diuretics in persistent cases
Prognosis
The prognosis of hematuria in children varies widely depending on the underlying cause:
- Many cases of isolated microscopic hematuria are benign and may resolve spontaneously
- Prognosis for glomerular causes depends on the specific condition and timely intervention
- Structural abnormalities may require surgical correction but often have good long-term outcomes
- Regular follow-up is essential to monitor for progression and adjust management as needed
Diagnostic Algorithm
Cola/brown urine?
Proteinuria (>30 mg/dL)?
RBC casts?
Acute nephritic syndrome?
YES
Glomerular hematuria
- CBC with differential
- Electrolytes, Ca
- BUN/Cr
- Serum protein/albumin
- Cholesterol
- C3/C4
- ASO/anti-DNase B
- ANA
- Antineutrophil antibody
- Throat/skin culture (if indicated)
- 24-hr urine total protein creatinine clearance
NO
Extraglomerular hematuria
Step 1
- Urine culture
Step 2
- Urine calcium/creatinine
- Sickle prep (African American)
- Renal/bladder ultrasound
Step 3
- Urinalysis: siblings, parents
- Serum electrolytes, Cr, Ca
- If crystalluria, urolithiasis, or nephrocalcinosis:
- 24-hr urine for Ca, creatinine, uric acid, oxalate
- If hydronephrosis/pyelocaliectasis:
- Cystogram, ± renal scan
Hematuria in Children
- What is the definition of macroscopic hematuria? Visible blood in the urine
- How is microscopic hematuria defined in children? ≥5 red blood cells per high-power field on microscopic urinalysis
- What is the most common cause of isolated microscopic hematuria in children? Idiopathic hypercalciuria
- Which condition is the most common glomerular cause of gross hematuria in children? IgA nephropathy (Berger's disease)
- What non-glomerular condition commonly causes gross hematuria in children? Urinary tract infection
- How can glomerular hematuria be distinguished from non-glomerular hematuria? Presence of red cell casts and dysmorphic red blood cells in glomerular hematuria
- What is the "coca-cola" colored urine typically associated with? Acute glomerulonephritis
- Which imaging study is typically first-line in evaluating hematuria in children? Renal ultrasound
- What is the most common metabolic cause of hematuria in children? Hypercalciuria
- How is hypercalciuria diagnosed in children? Urinary calcium-to-creatinine ratio >0.21 mg/mg in a random urine sample
- What is the role of urine culture in evaluating hematuria? To rule out urinary tract infection
- Which test can help differentiate between upper and lower urinary tract sources of bleeding? Three-tube test (initial, mid-stream, and terminal urine samples)
- What is the significance of protein-to-creatinine ratio in evaluating hematuria? Helps assess for concurrent proteinuria, suggesting glomerular disease if elevated
- Which hereditary condition should be considered in a child with hematuria and hearing loss? Alport syndrome
- What is the most common vascular cause of gross hematuria in children? Nutcracker syndrome (left renal vein compression)
- How does exercise-induced hematuria typically present? Transient hematuria following intense physical activity
- What is the appropriate initial management for asymptomatic microscopic hematuria? Observation and repeat urinalysis in 2-4 weeks
- When is a kidney biopsy indicated in a child with hematuria? Persistent hematuria with proteinuria, renal insufficiency, or systemic symptoms
- What is the role of complement C3 and C4 levels in evaluating hematuria? Low C3 suggests post-infectious glomerulonephritis or MPGN
- How does sickle cell disease cause hematuria? Renal papillary necrosis
- What is the most common cause of painful hematuria in children? Urinary tract infection
- Which tumor is the most common cause of hematuria in children under 5 years? Wilms tumor
- What is the role of urine cytology in evaluating hematuria in children? Limited role, mainly to rule out malignancy in adolescents
- How does the presence of proteinuria affect the evaluation of hematuria? Suggests glomerular disease and warrants more extensive workup
- What is the significance of a positive family history in a child with hematuria? Increases likelihood of hereditary conditions like Alport syndrome or thin basement membrane nephropathy
- How does thin basement membrane nephropathy typically present? Persistent microscopic hematuria without proteinuria or renal dysfunction
- What is the appropriate follow-up for a child with isolated microscopic hematuria? Annual urinalysis and blood pressure check
- How does IgA nephropathy typically present in children? Episodic gross hematuria often following upper respiratory infections
- What is the role of cystoscopy in evaluating hematuria in children? Limited, mainly for adolescents with unexplained gross hematuria
- How does the evaluation of hematuria differ between prepubertal and postpubertal children? Increased consideration of urological causes in postpubertal children
