What is the treatment for frequently relapsing nephrotic syndrome?

Treatment of Frequently Relapsing Nephrotic Syndrome

For children with frequently relapsing nephrotic syndrome (FRNS), we recommend 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

Initial Management of Relapses

• 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
• 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
• Recent evidence suggests that lower prednisone doses (1-1.5 mg/kg/day) may be effective for treating relapses while reducing cumulative steroid exposure 2
• 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

Corticosteroid-Sparing Therapy

Corticosteroid-sparing agents should be prescribed for children with FRNS who develop steroid-related adverse effects 1. Options include:

First-Line Options:

• Levamisole: 2.5 mg/kg on alternate days for at least 12 months 1, 3
• Cyclophosphamide: 2 mg/kg/day for 8-12 weeks (maximum cumulative dose 168 mg/kg) 1
  • Should only be started after achieving remission with corticosteroids
  • Second courses of alkylating agents should not be given

Alternative Options:

• Calcineurin inhibitors (cyclosporine or tacrolimus) 1

  • Cyclosporine: 4-5 mg/kg/day in two divided doses
  • Tacrolimus: 0.1 mg/kg/day in two divided doses (consider when cosmetic side effects of cyclosporine are unacceptable)
  • Monitor drug levels to limit toxicity
  • Continue for at least 12 months as most children relapse when therapy is stopped

• Mycophenolate mofetil (MMF): 1200 mg/m²/day in two divided doses for at least 12 months 1

• Rituximab: Consider only 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

Monitoring and Follow-up

• Monitor for steroid-related adverse effects including growth impairment, obesity, hypertension, diabetes, and osteoporosis 4
• Regular assessment of kidney function, especially in patients receiving calcineurin inhibitors 1
• Quantification of proteinuria to assess response to therapy 1

Indications for Kidney Biopsy

Consider kidney biopsy in children with FRNS in the following situations 1:

• Late failure to respond following initial response to corticosteroids
• High index of suspicion for a different underlying pathology
• Decreasing kidney function in children receiving calcineurin inhibitors

Special Considerations

• Children younger than 1 year are more likely to have a different (genetically definable) cause for their nephrotic syndrome and should be managed differently 1
• Adult patients with minimal change disease may have lower relapse rates compared to children but require similar treatment approaches 5
• The goal of therapy is to maintain remission with the lowest cumulative drug toxicity 6

Common Pitfalls and Caveats

• Avoid prolonged daily corticosteroid use due to significant adverse effects; transition to alternate-day therapy as soon as remission is achieved 1
• Do not start cyclophosphamide until the child has achieved remission with corticosteroids 1
• Avoid second courses of alkylating agents due to cumulative toxicity 1
• Remember that most children will relapse when corticosteroid-sparing agents are stopped, so treatment duration of at least 12 months is typically recommended 1
• Recognize that treatment choice should balance efficacy in maintaining remission against cumulative drug toxicity 6