What is the initial treatment for an adult with relapsing nephrotic syndrome?

Initial Treatment for Adults with Relapsing Nephrotic Syndrome

For adults with relapsing nephrotic syndrome, the initial treatment should be daily prednisone at 1 mg/kg/day until remission is achieved for at least 3 consecutive days, followed by alternate-day prednisone for at least 3 months. 1

First-Line Treatment Algorithm

1. Initial Corticosteroid Therapy:

   • Administer oral prednisone at 1 mg/kg/day (maximum 60 mg/day) until remission is achieved 1
   • Continue daily prednisone for at least 3 days after achieving complete remission 2
   • Complete remission is defined as reduction of proteinuria to normal levels (<0.3 g/day) 1

2. Maintenance Phase:

   • Transition to alternate-day prednisone (1 mg/kg or approximately 40 mg on alternate days) 1
   • Continue alternate-day therapy for at least 3 months with gradual tapering 1, 2
   • Prolonged therapy reduces risk of subsequent relapses 3

3. Response Monitoring:

   • Most adults achieve remission within 8 weeks, though it may take up to 16 weeks 1, 3
   • Regular monitoring of proteinuria is essential to assess response 2
   • If no response after 16 weeks, consider kidney biopsy to reassess diagnosis 1

Corticosteroid-Sparing Strategies

For patients with frequent relapses (≥2 episodes within 6 months) or steroid dependence, consider the following options:

1. Calcineurin Inhibitors:

   • Cyclosporine (3-5 mg/kg/day in divided doses) for at least 12 months 1
   • Target trough blood levels of 4-8 ng/ml 4
   • Tacrolimus is an alternative with potentially fewer cosmetic side effects 4

2. Cytotoxic Agents:

   • Cyclophosphamide (2-2.5 mg/kg/day) for 8-12 weeks (maximum cumulative dose <200 mg/kg) 1, 3
   • Complete remission has been reported in 81% of steroid-sensitive adults 1
   • Monitor for bone marrow suppression, hemorrhagic cystitis, and gonadal toxicity 3

3. Mycophenolate Mofetil (MMF):

   • Consider in patients who cannot tolerate calcineurin inhibitors or cyclophosphamide 1
   • Typically administered at 1200 mg/m²/day in two divided doses 2
   • May induce stable remission but data from large randomized trials are limited 1

Special Considerations

1. Infection Prevention:

   • During episodes of upper respiratory infections, increase prednisone to daily dosing (0.5 mg/kg/day) for 5-7 days to prevent relapse 1
   • This approach is particularly important for patients with a history of infection-triggered relapses 2

2. Dose Optimization:

   • Recent evidence suggests that lower prednisone doses (1-1.5 mg/kg/day) may be equally effective for treating relapses while reducing cumulative steroid exposure 5
   • Consider this approach in patients at high risk for steroid toxicity 5

3. Alternative Initial Approach:

   • For patients with severe nephrotic syndrome or contraindications to oral steroids, consider intravenous methylprednisolone (0.8 mg/kg/day) for 10 days followed by tacrolimus monotherapy 4
   • This approach has shown similar efficacy to conventional steroid therapy with fewer adverse events 4

Common Pitfalls and Caveats

• Steroid Toxicity: Prolonged daily corticosteroid use should be avoided due to significant adverse effects including glucose intolerance, cushingoid features, infections, and hip osteonecrosis 1, 2

• Treatment Duration: Insufficient duration of initial steroid therapy increases relapse risk; ensure adequate maintenance phase of at least 3 months 3

• Cyclophosphamide Timing: Only initiate cyclophosphamide after achieving remission with corticosteroids 2

• Second Courses: Avoid repeated courses of alkylating agents due to cumulative toxicity, particularly gonadal toxicity and oncogenicity risk 1, 2

• Calcineurin Inhibitor Withdrawal: Relapses are common following withdrawal of calcineurin inhibitors; consider slow tapering over several months 1

• Monitoring Requirements: Regular assessment of kidney function is essential, especially in patients receiving calcineurin inhibitors 2