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.

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

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.