Approach to hematuria

graph TD
    subgraph "Initial Evaluation"
        A[Child Presents with Hematuria] --> B{Initial Assessment: History & Physical Exam};
        B --> C{Determine Nature of Hematuria};
        C -->|Gross or Persistent Microscopic| D[Initiate Workup];
        C -->|Transient/Isolated Microscopic| E[Monitor & Re-evaluate];
    end

    subgraph "Diagnostic Workup"
        D --> F{Urinalysis & Urine Microscopy};
        F -->|Dysmorphic RBCs, RBC Casts, Proteinuria| G(Glomerular Pathway);
        F -->|Eumorphic RBCs, No Casts| H(Non-Glomerular Pathway);
    end

    subgraph "Glomerular Pathway"
        G --> I{Blood Tests: BUN/Cr, Complements, ASO};
        I --> J[Refer to Pediatric Nephrologist];
        J --> K[Further Workup e.g., Kidney Biopsy & Specific Treatment];
    end

    subgraph "Non-Glomerular Pathway"
        H --> L{Check for Associated Signs};
        L -->|Pyuria/Bacteriuria| M[UTI Workup: Urine Culture --> Treat];
        L -->|Crystals/Pain| N[Stone Workup: Renal Ultrasound, Urine Ca/Cr --> Manage];
        L -->|No Specific Signs| O[Imaging: Renal & Bladder Ultrasound];
        O -->|Abnormal| P[Refer to Urology/Nephrology];
        O -->|Normal| Q[Consider other causes: Trauma, Bleeding Disorder, Nutcracker Syndrome];
    end
    
    subgraph "Monitoring Pathway"
        E --> R{Periodic Urinalysis & Blood Pressure Checks};
        R -->|Remains Normal| S[Continue Observation];
        R -->|Develops Proteinuria, HTN, or Persists| T[--> Initiate Full Workup];
    end

Differential Diagnosis of Hematuria in a 3-Year-Old

• Hematuria is clinically defined as the persistent presence of more than 5 red blood cells (RBCs) per high-power field (hpf) in uncentrifuged urine, or more than 3 RBCs/hpf in a centrifuged sediment.
• The differential diagnosis for a 3-year-old presenting with hematuria is broad and is primarily divided into glomerular and non-glomerular etiologies.
• Upper urinary tract sources of hematuria originate within the nephron, including the glomerulus, tubular system, or interstitium.
• Lower urinary tract sources originate from the pelvicalyceal system, ureter, bladder, or urethra.

Category	Specific Etiologies	Clinical Correlates
Glomerular	Postinfectious Glomerulonephritis (PIGN)	Often follows a streptococcal throat or skin infection; presents with edema, oliguria, and hypertension.
	IgA Nephropathy	Coincides with upper respiratory or gastrointestinal infections; presents with recurrent gross hematuria.
	IgA Vasculitis (Henoch-Schönlein Purpura)	Systemic vasculitis presenting with a palpable purpuric rash, arthritis, abdominal pain, and nephritis.
	Hemolytic Uremic Syndrome (HUS)	Follows gastrointestinal illness; presents with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury.
	Alport Syndrome / Thin Basement Membrane Disease	Hereditary conditions presenting with persistent microscopic hematuria and a family history of kidney failure or deafness.
	Membranoproliferative Glomerulonephritis	Presents with mixed nephritic-nephrotic picture and persistent hypocomplementemia.
	Lupus Nephritis	Associated with systemic lupus erythematosus; presents with systemic signs such as rash and joint pain.
Non-Glomerular	Urinary Tract Infection (UTI)	The most common cause of gross hematuria; presents with dysuria, frequency, and fever.
	Idiopathic Hypercalciuria	Common metabolic cause; can present with painless gross or microscopic hematuria, or dysuria.
	Urolithiasis (Kidney Stones)	Presents with severe renal colic, flank pain, and hematuria.
	Anatomic Abnormalities	Includes hydronephrosis, multicystic dysplastic kidney, polycystic kidney disease, or Wilms tumor; often presents with a palpable abdominal mass.
	Trauma	Hematuria following blunt or penetrating injury to the abdomen or back.
	Coagulopathy / Bleeding Disorders	Hemophilia or thrombocytopenia can cause spontaneous urinary tract bleeding.
	Chemical / Hemorrhagic Cystitis	Associated with adenovirus infections or nephrotoxic medications like cyclophosphamide.

Clinical Evaluation and Diagnostic Approach

History and Physical Examination

• A meticulous history is required, focusing on the color of the urine (brown/cola-colored suggests glomerular; bright red suggests lower tract), timing in relation to the urinary stream, and associated symptoms like abdominal pain or dysuria.
• The clinician must inquire about recent upper respiratory, skin, or gastrointestinal infections, which can precipitate IgA nephropathy, postinfectious glomerulonephritis, or HUS.
• A family history of deafness, renal disease, polycystic kidneys, or urolithiasis is critical for diagnosing hereditary conditions like Alport syndrome or idiopathic hypercalciuria.
• Physical examination should assess for hypertension, facial or peripheral edema, and signs of heart failure, which are classic indicators of acute glomerulonephritis.
• The skin and joints should be examined for purpuric rashes and arthritis, suggesting IgA vasculitis or lupus, while the abdomen is palpated to rule out distended bladder, hydronephrosis, or tumors.
• Examination of the external genitalia is necessary to identify anatomic abnormalities, meatal stenosis, or local perineal irritation.

Distinguishing Glomerular vs. Non-Glomerular Hematuria

Feature	Glomerular Hematuria	Non-Glomerular Hematuria
Urine Color	Brown, cola, tea-colored, or smoky.	Bright red or pink.
Clots	Absent.	Often present.
Proteinuria	Usually >100 mg/dL (significant).	Usually <100 mg/dL (minimal).
RBC Morphology	>30% dysmorphic RBCs (acanthocytes).	>90% isomorphic (normal shape) RBCs.
Casts	RBC casts commonly present.	Absent.

Laboratory and Imaging Evaluation

• Urinalysis and phase-contrast microscopy are the first steps to quantify RBCs, detect RBC casts, and assess for dysmorphic cells characteristic of glomerular bleeding.
• A urine culture is mandatory to exclude urinary tract infection, especially in patients with dysuria or fever.
• A spot urine calcium-to-creatinine ratio is obtained; a value >0.2 mg/mg in children over 2 years of age suggests hypercalciuria.
• Blood tests should include a complete blood count (CBC), serum electrolytes, blood urea nitrogen (BUN), serum creatinine, and serum albumin to evaluate overall kidney function and detect complications.
• Serum complement levels (C3 and C4) are crucial for differentiation; C3 is transiently low in poststreptococcal GN, persistently low in membranoproliferative GN, and both C3 and C4 are low in lupus nephritis.
• Serological testing for antistreptolysin O (ASO) and anti-DNAse B titers confirms a preceding streptococcal infection.
• Renal and bladder ultrasonography is the primary imaging modality to rule out anatomic abnormalities, hydronephrosis, cystic disease, urolithiasis, and tumors.
• A kidney biopsy is indicated for patients with gross hematuria or persistent microscopic hematuria accompanied by decreased renal function, severe proteinuria, hypertension, or persistent hypocomplementemia lasting beyond 8 to 12 weeks.

Management of Hematuria

Asymptomatic Isolated Microscopic Hematuria

• Children with asymptomatic, isolated microscopic hematuria and a completely normal initial evaluation require conservative monitoring.
• Blood pressure and urinalysis should be checked every 3 months until the hematuria resolves; extensive diagnostic testing or invasive procedures like cystoscopy are usually unnecessary and costly.
• Referral to a pediatric nephrologist is recommended if the asymptomatic hematuria persists for more than 1 year or if proteinuria or hypertension develops.

Acute Glomerulonephritis (e.g., Poststreptococcal GN)

• The management of acute poststreptococcal glomerulonephritis is primarily supportive, aimed at treating the acute consequences of kidney dysfunction, volume overload, and hypertension.
• Sodium, potassium, and fluid intake must be strictly restricted until serum creatinine levels normalize and adequate diuresis is established.
• Mild to moderate edema and volume-dependent hypertension are managed with oral loop diuretics, such as furosemide (1-3 mg/kg).
• Patients with severe pulmonary edema, hypertensive emergencies, or congestive heart failure require intravenous furosemide (2-4 mg/kg) and continuous infusions of vasodilators or antihypertensive agents (e.g., nitroprusside, labetalol, or calcium channel blockers).
• Antibiotic therapy (e.g., penicillin) is administered if there is evidence of active streptococcal infection at the time of diagnosis, though it does not alter the natural history of the glomerulonephritis.
• Dialysis is infrequently required but is indicated in children with severe oliguria, life-threatening electrolyte disturbances (e.g., hyperkalemia), or fluid overload refractory to medical management.

IgA Vasculitis (Henoch-Schönlein Purpura) Nephritis

• Patients with mild kidney involvement (isolated microscopic hematuria or low-grade proteinuria) are monitored closely with weekly urinalysis and blood pressure checks during the active phase of the disease.
• For persistent proteinuria (>0.5–1 g/d/1.73 m²), conservative treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for at least 6 months is recommended to reduce proteinuria and slow disease progression.
• In patients with moderate to severe nephritis (nephrotic-range proteinuria, reduced glomerular filtration rate, or >50% crescents on biopsy), aggressive immunosuppressive therapy is indicated.
• Treatment regimens typically involve intravenous methylprednisolone pulses for 3 days, followed by a 3-month course of oral prednisone combined with immunosuppressive agents like azathioprine or mycophenolate mofetil.
• For the most severe, rapidly progressive crescentic presentations, therapy with cyclophosphamide or plasmapheresis in conjunction with corticosteroids is utilized to prevent end-stage kidney disease.

Hemolytic Uremic Syndrome (HUS)

• The diagnosis of HUS requires immediate hospitalization, as it is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury.
• The management of typical, Shiga toxin-associated HUS is primarily supportive, involving meticulous fluid and electrolyte balance, correction of volume deficits, and aggressive control of hypertension.
• Red blood cell transfusions are often necessary due to brisk and recurrent hemolysis; however, platelet transfusions are generally contraindicated as they may exacerbate microvascular thrombosis.
• Early institution of dialysis is indicated for patients who become significantly oliguric or anuric, or develop medically refractory hyperkalemia.
• For atypical HUS (aHUS) caused by complement dysregulation, the primary initial therapy is the prompt initiation of plasma exchange (PEX).
• Eculizumab, a terminal complement inhibitor, is indicated for aHUS patients demonstrating incomplete remission with plasma therapy, those with life-threatening features, or those with identified inherited defects in complement regulation.

IgA Nephropathy

• IgA nephropathy typically follows a benign course in childhood but requires long-term follow-up as progressive kidney dysfunction can occur in adulthood.
• First-line management for significant proteinuria involves renin-angiotensin system blockade with ACE inhibitors or ARBs to lower proteinuria and preserve renal function.
• If significant proteinuria persists despite maximal ACE inhibitor therapy, the addition of oral corticosteroids for 6 months is indicated to induce remission.
• Tonsillectomy may be considered in children where tonsils act as an infectious focus triggering recurrent gross hematuria.

Hypercalciuria and Urolithiasis

• Treatment of idiopathic hypercalciuria centers on high fluid intake and a diet restricted in sodium and animal protein.
• If dietary measures fail, oral thiazide diuretics are utilized to stimulate calcium reabsorption in the tubules, normalizing urinary calcium excretion and resolving hematuria.
• For active urolithiasis, pain management with nonsteroidal anti-inflammatory drugs and adequate hydration are prioritized; small ureteral stones (<5 mm) frequently pass spontaneously.
• Medical expulsive therapy, such as an alpha-adrenergic blocker (e.g., tamsulosin), may facilitate the passage of distal ureteral stones.

Urinary Tract Infections (UTI)

• Acute cystitis and pyelonephritis should be treated promptly with empiric antibiotics, modified subsequently based on urine culture sensitivity results.
• Oral antibiotics for 7 to 10 days are generally safe and effective for uncomplicated UTIs in stable, outpatient children.
• Parenteral antibiotic therapy is recommended for young infants, children with severe dehydration, emesis, or those at risk for urosepsis, transitioning to oral therapy once the patient is clinically stable.