Mycophenolate mofetil and prednisolone therapy in children with steroid-dependent nephrotic syndrome

Am J Kidney Dis. 2003 Dec;42(6):1114-20. doi: 10.1053/j.ajkd.2003.08.011.

Abstract

Background: A proportion of patients with steroid-dependent nephrotic syndrome (SDNS) experience frequent relapses despite long-term treatment with steroids, levamisole, or/and cyclophosphamide. We prospectively examined the efficacy of long-term therapy with mycophenolate mofetil (MMF) as a steroid-sparing agent in this group.

Methods: Nineteen patients with a mean age of 99.1 months (95% confidence interval [CI], 85.3 to 113) who had previously undergone long-term therapy with prednisolone (n = 19), levamisole (n = 16), and cyclophosphamide (n = 15), but had continued to show steroid dependence over many years, were studied. Renal biopsy showed minimal change disease and focal segmental glomerulosclerosis in 10 and 3 patients, respectively. Patients were administered MMF at a mean dose of 29 mg/kg/d (95% CI, 27.4 to 30.7) in 2 divided doses and decreasing doses of alternate-day prednisolone for a mean of 11.8 months (95% CI, 11.4 to 12.2). Relapses were treated with daily prednisolone until remission, with tapering later. They were additionally followed up for a mean of 17 months (95% CI, 15.9 to 18.1).

Results: Mean relapse rates decreased from 6.6 (95% CI, 5.4 to 7.7) to 2 episodes/y (95% CI, 1.2 to 2.7) during MMF treatment (P < 0.0001). Four patients each had 0, 1, 2, and 3 relapses; failure of MMF therapy (>3 relapses during treatment) was seen in 3 patients. Treatment with MMF resulted in steroid sparing, with a reduction in mean prednisolone dose from 0.7 (95% CI, 0.6 to 0.8) to 0.3 mg/kg/d (95% CI, 0.2 to 0.4; P < 0.0001). Fourteen patients showed a 50% or greater reduction in relapse rates; prednisolone therapy could be discontinued for 6 or more months in 8 patients. No significant gastrointestinal or hematologic side effects of MMF treatment were noted. After discontinuation of MMF treatment, 68.4% of patients had an increased frequency of relapses and recurrence of steroid dependence, requiring treatment with other medications.

Conclusion: Long-term therapy with MMF results in significant steroid sparing and reduction in relapse rates in patients with SDNS. Therapy with MMF and tapering doses of prednisolone appears to be a promising intervention in children with SDNS.

Publication types

  • Clinical Trial

MeSH terms

  • Child
  • Child, Preschool
  • Cyclophosphamide / therapeutic use
  • Cyclosporine / therapeutic use
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Glomerulosclerosis, Focal Segmental / complications
  • Glomerulosclerosis, Focal Segmental / drug therapy
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Infant
  • Levamisole / therapeutic use
  • Male
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacology
  • Mycophenolic Acid / therapeutic use*
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / etiology
  • Prednisolone / administration & dosage
  • Prednisolone / therapeutic use*
  • Prospective Studies
  • Recurrence
  • Remission Induction
  • Safety
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Levamisole
  • Cyclosporine
  • Cyclophosphamide
  • Prednisolone
  • Mycophenolic Acid