What is the initial treatment for nephrotic syndrome?

Initial Treatment of Nephrotic Syndrome

The initial treatment for nephrotic syndrome is oral prednisone at 60 mg/m²/day (maximum 60 mg) as a single daily dose for 6 weeks, followed by 40 mg/m² on alternate days for another 6 weeks, then tapered over 4 weeks for a total treatment duration of 16 weeks. 1

Corticosteroid Protocol

For Children (First-Line Treatment)

• Start prednisone 60 mg/m²/day (maximum 60 mg) as a single morning dose for 6 weeks daily 1, 2
• After 6 weeks, switch to 40 mg/m² on alternate days for another 6 weeks 1
• Taper by 10 mg/m² per week down to 5 mg on alternate days over the final 4 weeks 1
• Total treatment duration: 16 weeks 1

For Adults

• Prednisone 1 mg/kg/day (maximum 80 mg) or alternate-day dosing at 2 mg/kg (maximum 120 mg) 2, 3, 4
• Continue high-dose therapy for minimum 4 weeks if complete remission achieved, up to 16 weeks if remission not achieved 2, 3, 4
• After remission, taper slowly over 6 months 3, 4

Critical Dosing Consideration

• Do not use 2 mg/kg/day interchangeably with 60 mg/m²/day in children weighing <30 kg, as 2 mg/kg provides significantly lower doses (approximately 85% of the BSA-based dose) 5
• This underdosing may contribute to treatment failure in smaller children 5

Immediate Supportive Management (Concurrent with Steroids)

Edema Control

• Loop diuretics (furosemide) as first-line for severe edema and anasarca 2
• Restrict dietary sodium to <2.0 g/day 2, 4
• Avoid routine IV albumin infusions; use only if clinical hypovolemia present (hypotension, tachycardia, poor perfusion), not based on serum albumin levels alone 2
• Avoid IV saline administration, which worsens edema 2

Proteinuria Management

• Initiate ACE inhibitors or ARBs at maximally tolerated doses for proteinuria and blood pressure control 4
• Target systolic blood pressure <120 mmHg in adults using standardized office measurement 4

Alternative First-Line Therapy (When Steroids Contraindicated)

Consider calcineurin inhibitors (CNIs) as first-line therapy for patients with contraindications to high-dose corticosteroids, including uncontrolled diabetes, severe psychiatric conditions, severe osteoporosis, or morbid obesity with elevated HbA1c 2, 4

CNI Dosing

• Cyclosporine: 3-5 mg/kg/day in divided doses 2, 4
• Tacrolimus: 0.05-0.1 mg/kg/day (adults) or 0.1-0.2 mg/kg/day (children) in divided doses 2, 4

Infection Prevention (Start Immediately)

• Administer pneumococcal vaccination (23-valent or conjugate) before or early in immunosuppressive therapy 2, 3, 4
• Give annual influenza vaccination to patients and household contacts 2, 3, 4
• Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose immunosuppression 4

Monitoring During Initial Treatment

• Monitor urine protein daily using dipstick or spot urine protein-to-creatinine ratio 2
• Complete remission defined as: urine protein <200 mg/g (<20 mg/mmol) or trace/negative on dipstick for 3 consecutive days 2
• Regularly assess kidney function to evaluate treatment response 3, 4
• Monitor for medication side effects, particularly with long-term immunosuppressive therapy 3, 4

Critical Pitfalls to Avoid

• Do not declare steroid resistance until at least 8 weeks of adequate corticosteroid therapy completed 2, 3
• Do not stop therapy prematurely if partial response occurring; continue up to 16 weeks 2
• Do not use prophylactic anticoagulation routinely in adults without specific thrombotic risk assessment 6
• Do not defer kidney biopsy in adults before initiating immunosuppressive therapy 3
• In children with typical presentation, biopsy may be deferred if response to initial steroid therapy, but is indicated in steroid-resistant cases 3, 4

Special Considerations for Steroid-Sparing Agents

For frequently relapsing or steroid-dependent disease after initial treatment:

• Levamisole as first-line steroid-sparing agent if available, then cyclophosphamide 1
• Cyclophosphamide: 2 mg/kg once daily for 8-12 weeks (maximum cumulative dose 168 mg/kg) in children with minimal change disease who failed steroids 7
• Treatment beyond 90 days increases sterility risk in males 7
• Calcineurin inhibitors should be stopped if partial remission not achieved at 6 months 1