What is the initial treatment for nephrotic syndrome in children?

Initial Treatment for Nephrotic Syndrome in Children

The recommended initial treatment for nephrotic syndrome in children under 12 years without syndromic features is oral glucocorticoids (prednisone/prednisolone) at a dose of 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, with a total treatment duration of 8-12 weeks. 1, 2

Age-Based Approach

Children Under 12 Years:

• Without syndromic features or family history:
  • Start empiric glucocorticoid treatment without biopsy
  • Daily glucocorticoids for 4 or 6 weeks, followed by alternate-day therapy for an equal duration 1
  • Total treatment duration: 8-12 weeks

Children Over 12 Years or With Syndromic Features:

• Kidney biopsy and/or genetic testing is recommended
• Referral to specialty center
• Treatment based on biopsy findings 1, 2

Glucocorticoid Regimen Details

• Dosage: Prednisone/prednisolone 60 mg/m²/day (maximum 60 mg) as a single daily dose 2
• Initial phase: Daily dosing for 4-6 weeks
• Second phase: 40 mg/m²/day (maximum 40 mg) on alternate days for 4-6 weeks 2
• Administration: Medication should be taken in the morning as a single dose 3

Response Assessment

• Complete response: Continue with the standard regimen
• No response: Consider:
  • Genetic testing
  • Kidney biopsy
  • Calcineurin inhibitor
  • Renin-angiotensin-aldosterone system blockade 1

Evidence Strength and Considerations

The KDIGO 2025 guidelines provide strong evidence (1B recommendation) for the 8-12 week glucocorticoid regimen 1. This recommendation is based on multiple studies showing that longer initial treatment courses (8-12 weeks) result in significantly higher sustained remission rates compared to shorter courses.

Research has demonstrated that longer initial treatment (12 weeks) results in a significantly higher rate of sustained remissions after 2 years compared to standard 8-week treatment (49% vs 19%, P = 0.0079) 4. Additionally, the proportion of children developing frequent relapses is lower with longer initial treatment (29% vs 57%, P = 0.03).

Important Pitfalls to Avoid

1. Inadequate treatment duration: Ensure a minimum of 4 weeks of high-dose treatment with a total course of 8-12 weeks 2

2. Rapid steroid tapering: This increases relapse risk; follow the recommended alternate-day schedule for the second phase of treatment 2

3. Overlooking infection prevention: Regular monitoring for infections is crucial as they can trigger relapses 2

4. Failure to monitor for complications: Watch for:

   • Short-term: Hypovolemia, acute kidney injury, infections, thrombosis
   • Long-term: Growth retardation, hypertension, cataracts, osteoporosis 2

5. Not implementing supportive care: Include blood pressure control, sodium restriction, and diuretics for edema management while initiating steroid therapy 2

Special Considerations

• Pneumococcal and annual influenza vaccination are recommended
• Defer live vaccines until prednisone dose is <1 mg/kg/day 2
• For children with frequent relapses, additional therapies may be considered, including:
  • Levamisole (2.5 mg/kg on alternate days)
  • Cyclophosphamide (2 mg/kg/day for 8-12 weeks, maximum cumulative dose 168 mg/kg)
  • Calcineurin inhibitors
  • Mycophenolate mofetil 1, 2, 3

The evidence strongly supports the 8-12 week glucocorticoid regimen as the most effective initial approach for children with nephrotic syndrome, balancing efficacy in achieving remission with minimizing the risk of relapse.