What is the initial treatment for nephrotic syndrome?

Initial Treatment for Nephrotic Syndrome

Begin oral prednisone at 60 mg/m²/day (maximum 60 mg) as a single daily dose for 4-6 weeks, followed by alternate-day dosing at 40 mg/m² for 2-5 months with gradual tapering, for a total treatment duration of at least 12 weeks. 1, 2

Immediate Supportive Management

Before or concurrent with corticosteroid initiation, address the following:

• Edema control: Administer loop diuretics (furosemide) as first-line therapy for severe edema and anasarca 1
• Sodium restriction: Limit dietary sodium to <2.0 g/day to reduce fluid retention 1
• Avoid routine albumin infusions: Use intravenous albumin only if clinical indicators of hypovolemia are present (hypotension, tachycardia, poor perfusion)—not based on serum albumin levels alone 1
• Avoid intravenous saline: This can worsen edema in nephrotic syndrome 1

Corticosteroid Protocol: Detailed Dosing

For Children (Pediatric Nephrotic Syndrome)

Initial episode:

• Prednisone 60 mg/m²/day (maximum 60 mg) as a single morning dose for 6 weeks 3, 1
• Followed by 40 mg/m² on alternate days for 6 weeks 3
• Then taper at 10 mg/m² per week down to 5 mg on alternate days 3
• Total duration: 16 weeks 3

Important dosing consideration: The 2 mg/kg/day dosing is NOT equivalent to 60 mg/m²/day in children weighing <30 kg—the weight-based dose delivers significantly less medication 4. Always use body surface area dosing for accuracy 4.

For Adults

• Prednisone 1 mg/kg/day (maximum 80 mg) as a single daily dose, OR alternate-day dosing at 2 mg/kg (maximum 120 mg) 1, 2
• Continue high-dose therapy for minimum 4 weeks if complete remission achieved 1
• If no remission, continue up to 16 weeks before declaring steroid resistance 1, 2
• After remission, taper slowly over 6 months 2

Defining Treatment Response and Resistance

Complete remission criteria:

• Urine protein <200 mg/g (<20 mg/mmol) OR trace/negative on dipstick for 3 consecutive days 1, 2
• Monitor daily with urine dipstick or spot protein-to-creatinine ratio 1

Steroid resistance definition:

• Critical pitfall: Do NOT declare steroid resistance until at least 8 weeks of adequate corticosteroid therapy 1, 2
• However, the Canadian Society of Nephrology suggests 4-8 weeks may be reasonable to avoid prolonged steroid toxicity in clearly resistant cases 3
• Approximately 95% of responders achieve remission by 4 weeks, nearly 100% by 8 weeks 3

Managing Relapses

Infrequent relapses:

• Prednisone 60 mg/m² (maximum 60 mg/day) daily until remission for at least 3 days 3, 1
• Then taper over 4 weeks 3

Frequent relapses or steroid-dependent disease:

• Daily prednisone until remission for at least 3 days 3, 1
• Followed by alternate-day prednisone for at least 3 months 1
• Consider steroid-sparing agents (see below) 1

Alternative First-Line Therapy (When Corticosteroids Contraindicated)

For patients with contraindications to high-dose corticosteroids (uncontrolled diabetes, severe psychiatric conditions, severe osteoporosis, morbid obesity):

• Cyclosporine: 3-5 mg/kg/day in divided doses, targeting trough levels of 80-150 ng/mL 3, 1
• Tacrolimus: 0.1-0.2 mg/kg/day in divided doses (children) or 0.05-0.1 mg/kg/day (adults), targeting trough levels of 5-7 ng/mL 3, 1

Steroid-Resistant Nephrotic Syndrome (After 8 Weeks)

• First-line for steroid resistance: Calcineurin inhibitors (cyclosporine or tacrolimus) at doses above 3, 2
• Continue CNI therapy for minimum 6 months 2
• If at least partial remission achieved by 6 months, continue for minimum 12 months 2
• Stop CNI if no partial or complete remission achieved by 6 months 3, 2
• Do NOT use cyclophosphamide in children with steroid-resistant disease—tacrolimus is superior 3
• Consider mycophenolate mofetil if CNI-related adverse effects occur 3

Critical Infection Prevention

Before or early in immunosuppressive therapy:

• Pneumococcal vaccination (23-valent or conjugate vaccine) 1, 2
• Annual influenza vaccination for patients and household contacts 1, 2
• Consider prophylactic trimethoprim-sulfamethoxazole for high-dose immunosuppression 5
• Contraindication: Live vaccines are contraindicated during immunosuppressive therapy 2

Kidney Biopsy Indications

Defer biopsy in children if:

• Typical presentation (age 1-10 years, no systemic features) 2, 5
• Response to initial steroid therapy 2, 5

Perform biopsy if:

• Steroid-resistant nephrotic syndrome (after 8 weeks) 2, 5
• Atypical features (age <1 year or >10 years, hematuria, hypertension, low complement) 5
• Adults: Generally indicated before initiating immunosuppressive therapy 2

Common Pitfalls to Avoid

• Do not stop therapy prematurely: If partial response is occurring, continue up to 16 weeks 1
• Do not use weight-based dosing in small children: This underdoses by approximately 15% in children <30 kg 4
• Do not declare resistance too early: Wait full 8 weeks unless clearly resistant at 4-6 weeks with significant toxicity 3, 1
• Do not use cyclophosphamide for steroid-resistant disease in children: Tacrolimus is more effective 3