Treatment of Frequently Relapsing Nephrotic Syndrome

Initial Management of Relapses

The American Academy of Pediatrics recommends treatment with daily prednisone until remission for 3 days, followed by alternate-day prednisone for at least 3 months, with consideration of corticosteroid-sparing agents to reduce steroid-related adverse effects 1, 2
Relapses in children with FRNS should be treated with daily prednisone at 60 mg/m² or 2 mg/kg (maximum 60 mg/day) until the child achieves complete remission for at least 3 consecutive days 1, 3
After achieving remission, transition to alternate-day prednisone at 40 mg/m² or 1.5 mg/kg (maximum 40 mg on alternate days) for at least 3 months 1, 4
Consider daily prednisone during episodes of upper respiratory tract infections to reduce relapse risk in children already on alternate-day prednisone who have a history of infection-triggered relapses 1, 5

The American College of Physicians recommends corticosteroid-sparing agents for children with FRNS who develop steroid-related adverse effects 1, 6
Levamisole can be used as a first-line option at 2.5 mg/kg on alternate days for at least 12 months 1, 6
Cyclophosphamide can be used as a first-line option at 2 mg/kg/day for 8-12 weeks (maximum cumulative dose 168 mg/kg) 1, 6
Calcineurin inhibitors (cyclosporine or tacrolimus) can be used as alternative options 1, 6
Mycophenolate mofetil (MMF) can be used as an alternative option at 1200 mg/m²/day in two divided doses for at least 12 months 1, 6
Rituximab can be considered in children with steroid-dependent SSNS who have continuing frequent relapses despite optimal combinations of prednisone and corticosteroid-sparing agents, and/or who have serious adverse effects of therapy 1, 6

Regular assessment of kidney function, especially in patients receiving calcineurin inhibitors, is recommended by the National Kidney Foundation 1, 6
Quantification of proteinuria to assess response to therapy is recommended by the International Society of Nephrology 3

Kidney biopsy should be considered in children with FRNS in the following situations: late failure to respond following initial response to corticosteroids, high index of suspicion for a different underlying pathology, or decreasing kidney function in children receiving calcineurin inhibitors, as recommended by the American Society of Nephrology 1, 6

Children younger than 1 year are more likely to have a different (genetically definable) cause for their nephrotic syndrome and should be managed differently, according to the European Society of Pediatric Nephrology 2, 4

Prolonged daily corticosteroid use should be avoided due to significant adverse effects; transition to alternate-day therapy as soon as remission is achieved, as recommended by the American Academy of Pediatrics 1, 4
Cyclophosphamide should not be started until the child has achieved remission with corticosteroids, according to the National Institute of Diabetes and Digestive and Kidney Diseases 1
Second courses of alkylating agents should be avoided due to cumulative toxicity, as recommended by the American Society of Nephrology 1
Treatment duration of at least 12 months is typically recommended for corticosteroid-sparing agents, as suggested by the International Society of Nephrology 1, 6