What is the initial treatment for nephrotic syndrome in children?

Initial Treatment for Nephrotic Syndrome in Children

The initial treatment for nephrotic syndrome in children should be oral prednisone at a dose of 60 mg/m²/day (maximum 60 mg) given as a single daily dose for 4-6 weeks, followed by alternate-day prednisone at 40 mg/m² (maximum 40 mg) for another 2-5 months with tapering of the dose. 1

Diagnostic Criteria and Initial Evaluation

• Nephrotic syndrome is defined by proteinuria severe enough to cause hypoalbuminemia, edema, and hyperlipidemia 2
• Children under 6 years of age without hypertension, azotemia, hypocomplementemia, or signs of systemic illness have approximately 85% chance of responding to corticosteroid therapy 2
• Children younger than 1 year are more likely to have a genetically definable cause for nephrotic syndrome and should be managed differently 1

Initial Corticosteroid Treatment Protocol

Daily Dosing Phase:

• Begin with oral prednisone 60 mg/m²/day or 2 mg/kg/day (maximum 60 mg/day) as a single daily dose 1
• Continue daily dosing for 4-6 weeks 1
• Single daily dosing is as effective as divided doses and improves compliance 3

Alternate-Day Phase:

• After the daily phase, transition to alternate-day prednisone at 40 mg/m² or 1.5 mg/kg (maximum 40 mg on alternate days) 1
• Continue alternate-day dosing for 2-5 months with gradual tapering 1
• Total treatment duration should be at least 12 weeks to reduce relapse risk 1

Treatment Response and Monitoring

• Remission is defined as urine protein <1+ on dipstick for 3 consecutive days or uPCR <200 mg/g (<20 mg/mmol) 1
• Most children (94% with minimal change disease) will respond to this initial corticosteroid regimen 2
• Response typically occurs within 7-10 days of starting treatment 3
• Monitor for side effects of corticosteroids including growth failure, obesity, hypertension, and bone complications 2

Management of Relapses

• Relapse is defined as ≥3+ protein on urine dipstick for 3 consecutive days or uPCR ≥2000 mg/g (≥200 mg/mmol) 1
• For infrequent relapses, treat with prednisone 60 mg/m²/day (maximum 60 mg/day) until remission for at least 3 days 1
• After achieving remission, switch to alternate-day prednisone (40 mg/m² or 1.5 mg/kg) for at least 4 weeks 1
• For frequent relapses or steroid-dependent nephrotic syndrome, consider steroid-sparing agents 1, 4

Special Considerations

• During episodes of upper respiratory tract infections or other infections in children with frequent relapses, daily prednisone at 0.5 mg/kg/day for 5-7 days may reduce relapse risk 1
• Lower doses of prednisone (1-1.5 mg/kg/day) may be effective for treating relapses while reducing cumulative steroid exposure 5
• For steroid-dependent or frequently relapsing nephrotic syndrome, steroid-sparing agents should be considered, including:
  • Cyclophosphamide (2 mg/kg/day orally for 8-12 weeks, maximum cumulative dose 168 mg/kg) 4, 2
  • Calcineurin inhibitors (cyclosporine, tacrolimus) 1, 6
  • Mycophenolate mofetil 6
  • Rituximab 1, 6

Common Pitfalls and Caveats

• Avoid treating children under 1 year of age with the standard regimen without further evaluation, as they often have genetic forms of nephrotic syndrome 1
• Do not discontinue steroids too rapidly, as this increases relapse risk 1
• Be vigilant for complications of nephrotic syndrome including infections, thrombosis, and acute kidney injury 7, 6
• Monitor for steroid side effects and consider steroid-sparing agents in children with frequent relapses or steroid dependence 1, 2
• Recognize that approximately 80% of children will experience at least one relapse, and 50% will have frequent relapses or become steroid-dependent 1