What are the treatment guidelines for pediatric patients with nephrotic syndrome?

Treatment Guidelines for Pediatric Nephrotic Syndrome

The recommended initial treatment for nephrotic syndrome in children 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

Initial Treatment Approach

First-Line Therapy

• For children without syndromic features or family history:
  • Start empiric glucocorticoid treatment without biopsy 1
  • Oral prednisone/prednisolone as a single daily dose at 60 mg/m²/day (maximum 60 mg) 2
  • Daily dosing for 4-6 weeks, followed by alternate-day dosing at 40 mg/m²/day (maximum 40 mg) for 4-6 weeks 2
  • Total treatment duration: 8-12 weeks 2

Note: Body surface area-based dosing (60 mg/m²) is preferred over weight-based dosing (2 mg/kg), as weight-based dosing results in significantly lower doses for children under 30 kg 3

For Children with Syndromic Features or Family History

• Kidney biopsy and/or genetic testing is recommended before starting treatment 2
• Referral to a specialty center is advised 2

Management Based on Treatment Response

Complete Response (Steroid-Sensitive)

• Continue with standard regimen until completion 1
• For infrequent relapses:
  • Treat with prednisone 60 mg/m²/day until remission for at least 3 days 2
  • Follow with alternate-day prednisone (40 mg/m²) for at least 4 weeks 2

Frequently Relapsing or Steroid-Dependent Nephrotic Syndrome

• Consider corticosteroid-sparing agents when steroid-related adverse effects develop 2
• Options include (in no particular order of preference):
  1. Calcineurin inhibitors (cyclosporine 3-4 mg/kg/day or tacrolimus) 2, 1
  2. Cyclophosphamide (2 mg/kg/day for 8-12 weeks, maximum cumulative dose 168 mg/kg) 2, 1
  3. Levamisole (2.5 mg/kg on alternate days for 12-24 months) 1
  4. Mycophenolate mofetil (600-1200 mg/m²/day divided into 2 doses) 2, 1
  5. Rituximab for selected cases 2

No Response (Steroid-Resistant)

• Genetic testing and kidney biopsy 2, 1
• Calcineurin inhibitors as initial therapy 2
• Renin-angiotensin-aldosterone system blockade 2
• Consider mycophenolate mofetil for those who fail calcineurin inhibitor therapy 4

Management of Relapses

Prevention of Infection-Associated Relapses

• The 2025 KDIGO guidelines recommend against routinely giving daily glucocorticoids during episodes of upper respiratory tract and other infections to reduce relapse risk 2
• This represents a change from previous practice based on newer evidence

Treatment of Relapses

• For infrequent relapses: Single daily dose of prednisone 60 mg/m² until remission for at least 3 days, followed by alternate-day therapy 2
• For frequent relapses: Daily prednisone until remission for at least 3 days, followed by alternate-day prednisone for at least 3 months 2

Supportive Care

• Edema management: Sodium restriction and diuretics (furosemide is FDA-approved for nephrotic syndrome) 5
• Vaccinations: Pneumococcal and annual influenza vaccination; defer live vaccines until prednisone dose <1 mg/kg/day 1
• Monitoring: Regular assessment of proteinuria, renal function, blood pressure, weight, height, and presence of infections 1
• Infection prevention: Prompt treatment of infections 1

Potential Complications and Monitoring

• Short-term complications: Hypovolemia, acute kidney injury, infections, thrombosis 1
• Long-term complications: Growth retardation, hypertension, cataracts, osteoporosis, diabetes 1, 6
• Monitoring for pediatric patients on corticosteroids:
  • Blood pressure
  • Weight and height (growth velocity)
  • Intraocular pressure
  • Signs of infection
  • Psychosocial disturbances
  • Thromboembolism risk
  • Peptic ulcers
  • Cataracts
  • Osteoporosis 6

Common Pitfalls to Avoid

1. Inadequate initial steroid duration: Ensure minimum 4 weeks of high-dose treatment with total course of 8-12 weeks 1
2. Rapid steroid tapering: Avoid too rapid tapering of steroids 1
3. Delayed introduction of steroid-sparing agents in frequently relapsing or steroid-dependent cases 1
4. Overlooking infections which can trigger relapses 1
5. Inadequate monitoring of drug toxicity 1
6. Using weight-based dosing instead of body surface area-based dosing in young children, which may result in underdosing 3

The evidence strongly supports the efficacy of longer initial steroid courses (8-12 weeks) compared to shorter courses, with studies showing significantly higher sustained remission rates (49% vs 19%) and lower relapse rates with longer treatment durations 7.