Treatment of Nephrotic Syndrome
The first-line treatment for nephrotic syndrome is corticosteroids, specifically prednisone, with second-line agents including cyclophosphamide, calcineurin inhibitors, or levamisole used for steroid-dependent or frequently relapsing cases. 1
Initial Corticosteroid Therapy
For First Presentation
- Prednisone 60 mg/m²/day (maximum 60 mg) as a single daily dose for 4-6 weeks
- Followed by 40 mg/m²/day (maximum 40 mg) on alternate days for 4-6 weeks
- Total treatment duration: 8-12 weeks 1
- For adults: Lower doses on a per kilogram basis (1 mg/kg/day for 8 weeks), with treatment duration extended to ≥16 weeks to improve remission rates 2
Response Assessment
- In children: Remission typically occurs within 11 days
- In adults: May take up to 16 weeks 3
- Definition of remission: Negative or trace proteinuria for at least 3 consecutive days 1
Management of Relapses
Infrequent Relapses
- Prednisone 60 mg/m²/day until remission for at least 3 days
- Then alternate-day prednisone (40 mg/m²) for at least 4 weeks 1
Frequent Relapses (≥2 episodes within 6 months)
- Daily prednisone until remission for at least 3 days
- Then alternate-day prednisone for at least 3 months 1
- Consider steroid-sparing agents due to risk of steroid toxicity 2
Second-Line Therapy for Steroid-Dependent or Frequently Relapsing Cases
Alkylating Agents
- Cyclophosphamide: 2 mg/kg/day for 8-12 weeks (maximum cumulative dose 168 mg/kg) 2, 1
- Chlorambucil: 0.1-0.2 mg/kg/day for 8 weeks (maximum cumulative dose 11.2 mg/kg) 2
Calcineurin Inhibitors
- Cyclosporine: 3-5 mg/kg/day divided into 2 doses 2
- Tacrolimus: 0.1 mg/kg/day divided into 2 doses 1
- Target trough levels: 5 ng/ml 1
Other Options
- Levamisole: 2.5 mg/kg on alternate days for 12-24 months 2, 1
- Mycophenolate mofetil: 600-1200 mg/m²/day divided into 2 doses for 6-24 months 1
Monitoring and Follow-up
During Treatment
- Regular assessment of proteinuria
- Monitor renal function
- Blood pressure monitoring
- Growth monitoring in children (height, weight)
- Complete blood counts with alkylating agents or mycophenolate
- Drug levels for calcineurin inhibitors 1
Infection Prevention
- Pneumococcal and annual influenza vaccination
- Defer live vaccines until prednisone dose is <1 mg/kg/day 1
- Monitor for and promptly treat infections
Common Pitfalls and Complications
Treatment Pitfalls
- Inadequate initial steroid duration
- Rapid steroid tapering
- Delayed introduction of steroid-sparing agents
- Overlooking infections 1
Complications to Monitor
- Short-term: Hypovolemia, acute kidney injury, infections, thrombosis
- Long-term: Growth retardation, hypertension, cataracts, osteoporosis, diabetes 1
- Steroid-specific: Cushingoid features, glucose intolerance, hip osteonecrosis (particularly in elderly and post-menopausal women) 2
- Cyclophosphamide-specific: Bone marrow depression, hemorrhagic cystitis, hair loss, infertility 3
Special Considerations
Kidney Biopsy Indications
- Late steroid resistance
- Suspected secondary cause
- Diagnosis before 1 year or after 12 years of age
- Evaluation of nephrotoxicity due to calcineurin inhibitors 1
Treatment Goals
- Reduction in proteinuria by at least 25% by 3 months
- Reduction in proteinuria by 50% by 6 months 1
- Target proteinuria of <0.5-0.7 g/24h by 12 months 1
The treatment approach should be adjusted based on response, with careful monitoring for side effects and complications of both the disease and its treatments.