What is the initial treatment for nephrotic syndrome?

Initial Treatment for Nephrotic Syndrome

The initial treatment for nephrotic syndrome should be oral corticosteroids (prednisone or prednisolone) at a dose of 60 mg/m² per day (maximum 80 mg) as a single daily dose for 4-6 weeks, followed by alternate-day therapy at 40 mg/m² for an additional 4-6 weeks. 1

Corticosteroid Regimen for Initial Treatment

For Children:

• Initial phase: Prednisone 60 mg/m² per day (maximum 80 mg) as a single daily dose for 4-6 weeks
• Continuation phase: 40 mg/m² on alternate days for 4-6 weeks
• Tapering phase: Slow taper over a period of up to 6 months after achieving remission
• Total duration: 12-16 weeks including tapering 1

For Adults:

• Initial phase: Prednisone 1 mg/kg/day (maximum 80 mg) as a single daily dose for 4-8 weeks
• Continuation phase: Alternate-day therapy followed by slow tapering
• Total duration: Treatment may need to be continued for up to 16 weeks if complete remission is not achieved earlier 1

Response Assessment and Definitions

• Remission: Urine protein <1+ on dipstick or uPCR <200 mg/g for 3 consecutive days 1
• Relapse: Urine protein ≥3+ on dipstick for 3 consecutive days or uPCR ≥2000 mg/g 1
• Steroid resistance: Failure to achieve remission after a minimum of 8 weeks of corticosteroid therapy 1

Special Considerations

Patients with Contraindications to High-Dose Corticosteroids:

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

• Consider calcineurin inhibitors (CNIs) as first-line therapy instead 1
  • Cyclosporine: 3-5 mg/kg/day in divided doses
  • Tacrolimus: 0.05-0.1 mg/kg/day in divided doses

Pediatric Patients:

• Growth velocity should be monitored during treatment 2
• Pneumococcal and influenza vaccinations should be given 1
• Live vaccines should be deferred until prednisone dose is below 1 mg/kg daily or 2 mg/kg on alternate days 1

Management of Complications

1. Edema: Sodium restriction and judicious use of diuretics
2. Infections: Prompt recognition and treatment; consider prophylactic antibiotics in high-risk patients
3. Thromboembolism: Consider prophylactic anticoagulation in severe cases with significant hypoalbuminemia
4. Hyperlipidemia: For initial episodes, statins are not recommended 1

Common Pitfalls to Avoid

1. Underdosing in children: Using weight-based dosing (2 mg/kg/day) instead of BSA-based dosing (60 mg/m²/day) can lead to underdosing in children <30 kg 3

2. Premature discontinuation: Corticosteroids should be continued for the full recommended duration even after achieving remission to reduce risk of early relapse 1, 4

3. Inadequate monitoring: Regular monitoring for side effects of corticosteroids is essential, including blood pressure, weight, height (in children), and blood glucose 2

4. Failure to recognize steroid resistance: If no response after 8 weeks of treatment, the patient should be considered steroid-resistant and require kidney biopsy and alternative therapy 1

5. Missing secondary causes: Appropriate investigations should be performed to exclude secondary causes of nephrotic syndrome before initiating immunosuppressive therapy 1

The response to corticosteroids is an important prognostic indicator in nephrotic syndrome. Most children with minimal change disease (the most common cause of nephrotic syndrome in children) respond to corticosteroids within 2 weeks, while adults may take up to 16 weeks to achieve remission 4, 5. Patients who fail to respond to corticosteroids after 8 weeks should undergo kidney biopsy (if not already performed) to guide further management 1.