What is the initial treatment for nephrotic syndrome?

Initial Treatment for Nephrotic Syndrome

Begin oral prednisone at 60 mg/m²/day (or 2 mg/kg/day, maximum 60-80 mg/day) as a single daily dose for 4-6 weeks, followed by alternate-day dosing at 40 mg/m² (or 1.5 mg/kg, maximum 40 mg) for 2-5 months with gradual tapering, for a total treatment duration of at least 12 weeks. 1, 2

Age-Specific Considerations

• Children younger than 1 year require different management as they are more likely to have genetically definable causes of nephrotic syndrome and should not receive standard corticosteroid protocols without further evaluation 1
• In children with typical presentation (ages 1-10 years), kidney biopsy may be deferred if there is response to initial steroid therapy 2, 3
• Adults require longer treatment courses than children to achieve similar remission rates, and kidney biopsy is generally indicated before initiating immunosuppressive therapy 2, 4

Initial Corticosteroid Protocol

Daily Phase (4-6 weeks)

• Administer prednisone 60 mg/m²/day or 2 mg/kg/day (maximum 60 mg/day in children, 80 mg/day in adults) as a single daily dose 1, 2
• Continue daily dosing for minimum 4 weeks if complete remission is achieved, up to maximum 16 weeks if remission is not achieved 5, 2
• Use body surface area (BSA) dosing rather than weight-based dosing in children under 30 kg, as weight-based dosing results in significant underdosing (mean 16.6% lower dose) and increases the risk of frequent relapses 6, 7

Alternate-Day Phase (2-5 months)

• After the daily phase, transition to alternate-day prednisone at 40 mg/m² or 1.5 mg/kg (maximum 40 mg on alternate days) 1, 3
• Continue alternate-day dosing for 2-5 months with gradual tapering 1
• Total treatment duration should be at least 12 weeks to reduce relapse risk, with evidence supporting courses up to 6 months 5, 1

Tapering Strategy

• After achieving remission, taper corticosteroids slowly over a period of up to 6 months 5, 2
• Avoid rapid discontinuation, as this significantly increases relapse risk 1

Alternative First-Line Therapy

• For patients with relative contraindications or intolerance to high-dose corticosteroids (uncontrolled diabetes, psychiatric conditions, severe osteoporosis), consider calcineurin inhibitors (CNIs) as first-line therapy 5, 2, 3
• Cyclosporine dosing: 3-5 mg/kg/day in divided doses 5, 3
• Tacrolimus dosing: 0.05-0.1 mg/kg/day (or 0.1-0.2 mg/kg/day) in divided doses 5, 3

Defining Treatment Response

• Remission is defined as urine protein <1+ on dipstick for 3 consecutive days or urine protein-to-creatinine ratio (uPCR) <200 mg/g (<20 mg/mmol) 1
• Steroid resistance is defined after a minimum of 8 weeks of treatment with corticosteroids without achieving remission 2
• Approximately 80% of children will experience at least one relapse, and 50% will have frequent relapses or become steroid-dependent 1

Management of Relapses

Infrequent Relapses

• Relapse is defined as ≥3+ protein on urine dipstick for 3 consecutive days or uPCR ≥2000 mg/g (≥200 mg/mmol) 1
• Treat with prednisone 60 mg/m²/day (maximum 60 mg/day) until remission for at least 3 days 1
• After achieving remission, switch to alternate-day prednisone (40 mg/m² or 1.5 mg/kg) for at least 4 weeks 1

Frequent Relapses or Steroid-Dependent Disease

• Consider steroid-sparing agents including alkylating agents (cyclophosphamide or chlorambucil), levamisole, CNIs, or mycophenolate mofetil (MMF) 5, 1, 3
• Cyclophosphamide: 2 mg/kg/day for 8-12 weeks (maximum cumulative dose 168 mg/kg) 5
• Levamisole: 2.5 mg/kg on alternate days for at least 12 months 5
• CNIs (cyclosporine 3-5 mg/kg/day or tacrolimus 0.05-0.1 mg/kg/day) for 1-2 years 5
• MMF: 500-1000 mg twice daily for 1-2 years for patients intolerant of corticosteroids, cyclophosphamide, and CNIs 5

Supportive Management

• Restrict dietary sodium to <2.0 g/day to reduce edema and help manage proteinuria 3
• Use loop diuretics as first-line agents for edema management 3
• Initiate ACE inhibitors or ARBs at maximally tolerated doses for proteinuria and blood pressure control 3
• Target systolic blood pressure <120 mmHg in adults using standardized office BP measurement 3

Infection Prevention

• Administer pneumococcal vaccination to all patients with nephrotic syndrome 2, 3
• Provide annual influenza vaccination to patients and household contacts 2, 3
• Live vaccines are contraindicated in children receiving immunosuppressive agents 2
• During episodes of upper respiratory tract infections in children with frequent relapses, daily prednisone at 0.5 mg/kg/day for 5-7 days may reduce relapse risk 1

Common Pitfalls and Caveats

• Do not use weight-based dosing (2 mg/kg/day) in children weighing <30 kg, as this results in significant underdosing compared to BSA-based dosing (60 mg/m²/day) and increases the risk of frequent relapses by nearly twofold 6, 7
• Avoid treating infants under 1 year with standard protocols without genetic testing and specialized evaluation, as they often have genetic forms of nephrotic syndrome that do not respond to steroids 1
• Do not discontinue steroids too rapidly, as shorter treatment courses (mean 14 days daily + 16 days alternate-day) result in significantly lower sustained remission rates (19% vs 41%) and shorter remission duration (79 vs 169 days) compared to standard 8-week courses 8
• Monitor for steroid side effects including growth suppression in children, which may occur even without laboratory evidence of HPA axis suppression 9
• In adults, do not assume steroid resistance until after 4 months of daily steroid therapy, as adults respond more slowly than children and may require up to 16 weeks to achieve remission 5, 4
• Regularly assess proteinuria and kidney function to evaluate treatment response 2, 3