What is the recommended work‑up and initial management for a child presenting with new‑onset nephrotic syndrome?

Initial Management of New-Onset Nephrotic Syndrome in Children

For children under 12 years of age without syndromic features or family history, begin oral prednisone at 60 mg/m²/day (maximum 60 mg/day) for 4–6 weeks, followed by alternate-day dosing at 40 mg/m²/dose for an additional 2–5 months with gradual tapering. 1, 2

Age-Based Diagnostic and Treatment Algorithm

Children < 1 Year Old

• Do not initiate empiric corticosteroids—these infants likely have congenital nephrotic syndrome (CNS) requiring specialized evaluation 1
• Perform immediate infectious screening (CMV, toxoplasmosis, rubella, hepatitis B/C, HIV) and genetic testing 1
• Refer urgently to a specialized pediatric nephrology center due to disease complexity 1

Children 1–12 Years Old Without Syndromic Features

• Start empiric corticosteroid therapy without kidney biopsy 1, 2
• Administer prednisone 60 mg/m²/day (or 2 mg/kg/day, maximum 60 mg) as a single daily dose for 4–6 weeks 1, 2
• After achieving remission (typically within 4–6 weeks), switch to alternate-day prednisone 40 mg/m²/dose (or 1.5 mg/kg, maximum 40 mg) for 2–5 months with tapering 1, 2
• Total treatment duration should be at least 12 weeks 1, 2
• Approximately 85–90% of these children will achieve complete remission and have steroid-sensitive nephrotic syndrome 3, 4

Children > 12 Years Old OR Any Age with Syndromic Features

• Perform kidney biopsy and/or genetic testing before initiating therapy 1
• Syndromic features include impaired growth, skeletal/neurodevelopmental/ocular abnormalities, deafness, genital ambiguity, or facial dysmorphisms 1
• Refer to a specialty center for comprehensive evaluation 1

Initial Assessment and Workup

Diagnostic Criteria Confirmation

• Nephrotic-range proteinuria: ≥40 mg/m²/hour or urine protein/creatinine ratio ≥200 mg/mmol (approximately 3+ on dipstick) 5, 2
• Hypoalbuminemia: serum albumin <2.5 g/dL 5, 2
• Edema (typically present but not required for diagnosis) 5

Essential Laboratory Tests

• Complete blood count, comprehensive metabolic panel (sodium, potassium, chloride, bicarbonate, creatinine, urea) 2
• Serum albumin, total protein, cholesterol, triglycerides 2
• Ionized calcium, phosphate, magnesium 2
• Urinalysis with microscopy and spot urine protein/creatinine ratio 2
• Complement levels (C3, C4) to exclude secondary causes 1

Additional Testing Based on Presentation

• If age <1 year: infectious serology and genetic testing mandatory 1
• If atypical features (hematuria, hypertension, azotemia, hypocomplementemia): consider early biopsy 1, 6

Fluid and Volume Management

Assessment of Volume Status

Critical distinction: Nephrotic children have total body fluid overload but may have intravascular volume depletion 2, 7

Clinical indicators of hypovolemia include: 1, 2

• Prolonged capillary refill time (>2 seconds)
• Tachycardia
• Oliguria or anuria
• Abdominal discomfort or pain
• Hypotension (late finding)

Albumin Administration Guidelines

• Do NOT give albumin based solely on low serum albumin levels 1, 2
• Reserve albumin infusions for symptomatic hypovolemia with clinical indicators listed above 1, 2
• Dose: 1–4 g/kg intravenously when indicated 2
• Always administer furosemide 0.5–2 mg/kg at the end of albumin infusion to enhance diuresis and prevent volume overload 2

Fluid Restriction Strategy

• Avoid routine intravenous crystalloid fluids (normal saline) 1, 2
• Restrict oral fluids to insensible losses plus measured urine output 2
• Use concentrated high-calorie formulas if nutritional support needed 1

Diuretic Management: Critical Pitfalls to Avoid

When Diuretics Are Appropriate

• Only use loop diuretics when intravascular volume is adequate or overloaded (good peripheral perfusion, elevated blood pressure) 2
• Initial furosemide dose: 0.5–2 mg/kg per dose, oral or intravenous 2
• May dose up to 6 times daily, not exceeding 10 mg/kg/day total 2
• High-dose regimens (>6 mg/kg/day) should not continue beyond one week 2

Critical Contraindications

• Do NOT use diuretics in the presence of hypovolemia—this worsens volume depletion and dramatically increases thrombotic risk 2
• Discontinue immediately if anuria develops 2
• Intravenous furosemide must be infused over 5–30 minutes to reduce ototoxicity risk 2

Potassium-Sparing Diuretics

• Prefer amiloride over spironolactone when potassium-sparing effect needed 1, 2
• Rationale: Urinary proteases directly activate epithelial sodium channels (ENaC) independent of mineralocorticoid receptors, making spironolactone less effective 1
• Avoid all potassium-sparing agents if serum potassium >5.4 mEq/L 2

Monitoring During Diuretic Therapy

• Check electrolytes (especially potassium, sodium), blood pressure, and renal function regularly 2
• Watch for signs of hypovolemia development 2

Thrombosis Prevention

Risk Factors

• Serum albumin <2.9 g/dL significantly increases thrombotic event risk 2, 7
• Hypovolemia compounds this risk 2
• Loss of anticoagulant proteins (antithrombin III, protein C, protein S) in urine 7

Preventive Measures

• Avoid central venous catheters whenever possible due to high thrombosis risk 1, 2
• If central access required for repeated albumin infusions, administer prophylactic anticoagulation for duration of line placement 1
• Preserve peripheral vasculature for potential future dialysis access 2
• Maintain adequate hydration and avoid hypovolemia 2

Infection Prophylaxis and Monitoring

Increased Infection Risk

• Loss of immunoglobulins in urine predisposes to bacterial infections, particularly encapsulated organisms 7, 4
• Peritonitis, cellulitis, and sepsis are common complications 7
• Varicella infection can be severe in nephrotic children 7

Preventive Strategies

• Ensure age-appropriate vaccinations are current (avoid live vaccines during active immunosuppression) 4
• Maintain high index of suspicion for infections during relapses 4
• Consider pneumococcal vaccination if not previously administered 4

Response Assessment and Next Steps

Defining Remission

• Complete remission: proteinuria <0.2 g/g (or trace/negative on dipstick) on three consecutive early morning urine samples 3, 2
• Expected timeframe: 4–6 weeks of daily corticosteroids 2, 3

If No Response After 4–6 Weeks

• Consider kidney biopsy to exclude focal segmental glomerulosclerosis or other pathology 1, 2
• Initiate calcineurin inhibitor therapy (tacrolimus or cyclosporine) 1
• Add renin-angiotensin-aldosterone system blockade (ACE inhibitor or ARB) for antiproteinuric effect 1
• Refer to specialized pediatric nephrology center 1

Relapse Patterns (After Initial Response)

• Approximately 70–80% will experience at least one relapse 3, 4
• Up to 50% develop frequent relapses (≥2 in 6 months) or steroid dependence 3, 4
• For frequent relapsers or steroid-dependent patients, consider steroid-sparing agents: rituximab (preferred), calcineurin inhibitors, cyclophosphamide, levamisole, or mycophenolate mofetil 1, 8, 4

Common Pitfalls Summary

1. Do NOT give albumin based on laboratory values alone—only for symptomatic hypovolemia 1, 2
2. Do NOT use diuretics when hypovolemia is present—this exacerbates volume depletion and thrombosis risk 2
3. Do NOT choose spironolactone as first-line potassium-sparing diuretic—amiloride is superior due to mechanism of action 1, 2
4. Do NOT perform kidney biopsy in typical cases (age 1–12 years, no atypical features)—empiric corticosteroid therapy is appropriate 1
5. Do NOT use central venous catheters unless absolutely necessary—thrombosis risk is prohibitively high 1, 2
6. Do NOT confuse nephrotic syndrome with nephritic syndrome—the former has massive proteinuria and edema; the latter has hematuria and hypertension 2