What is the recommended initial treatment for pediatric patients with nephrotic syndrome?

Initial Treatment for Pediatric Nephrotic Syndrome

The recommended initial treatment for pediatric patients with nephrotic syndrome is prednisone or prednisolone at a daily single dose of 60 mg/m²/day (maximum 60 mg) 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

Diagnostic Approach and Initial Management

Before initiating treatment, consider these key points:

• Children under 12 years without atypical features can receive empiric glucocorticoid treatment without kidney biopsy 1
• Older children (≥12 years) or those with atypical features should undergo biopsy and/or genetic testing with referral to a specialty center 1
• Renal ultrasound is recommended to assess kidney size, echogenicity, and rule out structural abnormalities 1

Corticosteroid Treatment Protocol

First-Line Therapy

1. Initial high-dose phase:

   • Prednisone/prednisolone 60 mg/m²/day (maximum 60 mg) as a single daily dose for 4-6 weeks 1
   • Single daily dosing is effective and preferred over divided doses 2

2. Tapering phase:

   • Follow with 40 mg/m²/day (maximum 40 mg) on alternate days for 4-6 weeks 1
   • Total treatment duration should be 8-12 weeks 1

Important Dosing Considerations

• Using body surface area (BSA) for dosing is preferred over weight-based dosing (2 mg/kg/day), especially for children weighing <30 kg, as weight-based dosing may result in underdosing 3
• Longer treatment duration (3 months or more) significantly reduces relapse risk compared to shorter courses (2 months) 4, 5

Monitoring During Treatment

Regular monitoring is essential:

• Blood pressure, weight, and height 1, 6
• Signs of infection 1
• Intraocular pressure 6
• Potential steroid-related adverse effects 1, 6

Treatment Response Assessment

• Expect response within approximately 9-11 days of treatment initiation 2
• Goal: Complete remission (reduction in proteinuria)
• After achieving complete remission, steroids should be tapered slowly over 6 months 1

Common Pitfalls to Avoid

1. Inadequate initial treatment duration

   • Minimum of 4 weeks high-dose treatment is required 1
   • Total course should be 8-12 weeks 1

2. Rapid steroid tapering

   • Should be done slowly over 6 months after remission 1

3. Overlooking infections

   • Infections remain the most important cause of mortality 4
   • Pneumococcal and annual influenza vaccination recommended 1
   • Live vaccines should be deferred until prednisone dose <1 mg/kg/day 1

4. Inadequate monitoring for adverse effects

   • Growth velocity may be a sensitive indicator of systemic corticosteroid exposure 6
   • Monitor for obesity, hypertension, diabetes mellitus, osteoporosis, and adrenal suppression 6

Management of Steroid-Resistant Cases

If no response to initial steroid therapy:

• Consider intravenous high-dose methylprednisolone 7
• If methylprednisolone fails, calcineurin inhibitors (cyclosporine or tacrolimus) are the next line of treatment 1, 7
• Referral to pediatric nephrology specialists for histological and genetic diagnosis is recommended 7

Alternative Therapies for Special Situations

For patients with contraindications to high-dose steroids:

• Consider calcineurin inhibitors (CNIs) such as cyclosporine (3-4 mg/kg/day) or tacrolimus 1

For frequent relapses or corticosteroid dependence:

• Levamisole: 2.5 mg/kg on alternate days for 12-24 months 1
• Cyclophosphamide: 2 mg/kg/day for 8-12 weeks 1
• Mycophenolate mofetil: 600-1200 mg/m²/day divided into 2 doses 1