What is the initial treatment for a pediatric patient with nephrotic syndrome?

Initial Treatment for Pediatric Nephrotic Syndrome

Begin oral prednisone at 60 mg/m²/day or 2 mg/kg/day (maximum 60 mg/day) as a single morning dose for 4-6 weeks, followed by alternate-day prednisone at 40 mg/m² for 2-5 months, with total treatment duration of at least 12 weeks. 1, 2

Treatment Protocol

Daily Phase (Weeks 1-6)

• Administer prednisone 60 mg/m²/day or 2 mg/kg/day as a single morning dose (maximum 60 mg/day) 1, 2, 3
• Continue this daily dosing for the full 4-6 weeks regardless of when remission occurs 1, 4
• Single daily dosing is as effective as divided doses, with mean response time of 9.6 days for initial episodes and 11.1 days for relapses 3

Alternate-Day Phase (Weeks 7-24)

• Transition to alternate-day prednisone at 40 mg/m² or 1.5 mg/kg (maximum 40 mg on alternate days) 1, 2
• Continue for 2-5 months with gradual tapering 1, 2
• Longer initial treatment courses (up to 6-7 months total) significantly reduce relapse risk without increasing adverse effects 4, 5

Defining Treatment Response

• Remission: Urine protein <1+ on dipstick for 3 consecutive days OR urine protein-to-creatinine ratio <200 mg/g (<20 mg/mmol) 1, 4
• Steroid-sensitive: Approximately 85% of children achieve remission within 4 weeks of daily prednisone 6
• Steroid-resistant: No remission after 4-6 weeks of daily prednisone; requires minimum 8 weeks to definitively confirm 4, 6

Critical Age-Based Considerations

Infants (<1 year)

• Do NOT use standard corticosteroid regimen without further evaluation 1
• These children are more likely to have genetically definable causes requiring different management 1

Adolescents (>12 years)

• Require kidney biopsy BEFORE initiating treatment 4
• Higher likelihood of secondary causes or non-minimal change disease 4

Management of Relapses

Defining Relapse

• ≥3+ protein on urine dipstick for 3 consecutive days OR urine protein-to-creatinine ratio ≥2000 mg/g (≥200 mg/mmol) 1
• Approximately 80% of children experience at least one relapse 1

Infrequent Relapses

• Prednisone 60 mg/m²/day (maximum 60 mg/day) until remission for at least 3 consecutive days 1, 2
• Switch to alternate-day prednisone 40 mg/m² for 4 weeks 1, 2
• Shorter 2-week courses are adequate for relapses (unlike initial episodes) 5

Frequent Relapses or Steroid-Dependent Disease

• Consider steroid-sparing agents rather than continuing corticosteroids alone 2
• First-line options: Levamisole (2.5 mg/kg alternate days) or cyclophosphamide (2 mg/kg/day for 8-12 weeks) 2
• Alternative options: Mycophenolate mofetil, rituximab, or calcineurin inhibitors (cyclosporine/tacrolimus) 2

Infection-Related Relapse Prevention

• During upper respiratory tract infections in children with frequent relapses, consider daily prednisone 0.5 mg/kg/day for 5-7 days 1, 4

Steroid-Resistant Disease Management

• Use cyclosporine or tacrolimus as initial second-line therapy 2
• Kidney biopsy is mandatory in all children with steroid-resistant nephrotic syndrome except those with known infection/malignancy-associated disease or confirmed genetic causes 4
• Obtain genetic testing as soon as possible, ideally within 2 weeks of confirming steroid resistance 4
• Most steroid-resistant patients (80.5%-94.4%) have focal segmental glomerulosclerosis or mesangioproliferative glomerulonephritis 6

Common Pitfalls and How to Avoid Them

Duration Errors

• Do NOT use the shorter 8-week regimen (4 weeks daily + 4 weeks alternate-day) as this significantly increases relapse risk 4
• Do NOT discontinue steroids too rapidly 1
• Total treatment duration should be at least 12 weeks, with optimal duration up to 6 months for initial episodes 1, 5

Dosing Errors

• Single daily dosing is as effective as divided doses and should be preferred 3
• Maximum daily dose is 60 mg, maximum alternate-day dose is 40 mg 1, 2

Biopsy Timing

• Do NOT perform kidney biopsy before initial corticosteroid trial in children aged 1-12 years presenting with typical nephrotic syndrome 7
• Therapeutic response to corticosteroids remains the best prognostic marker 7, 6
• Approximately 94% of steroid-sensitive patients have minimal change disease 6

Population-Specific Considerations

• Black race, older age at presentation (>8 years), and female sex are independently associated with corticosteroid resistance 7
• The majority of blacks who are steroid-resistant have minimal change disease on biopsy, making histologic diagnosis unable to predict corticosteroid response 7

Monitoring Requirements

• Monitor for steroid side effects including growth suppression, hypertension, hyperglycemia, and bone density changes 8
• Growth velocity may be the most sensitive indicator of systemic corticosteroid exposure in pediatric patients 8
• Titrate to the lowest effective dose to minimize growth effects 8