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


CONCLUSIONS
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.
Bagga
Arvind
A
Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. arvindbagga@hotmail.com
Hari
Pankaj
P
Moudgil
Asha
A
Jordan
Stanley C
SC
D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D007978:Levamisole / Q000627:therapeutic use; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000209:etiology; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D012449:Safety; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D007978:Levamisole; D016572:Cyclosporine; D003520:Cyclophosphamide; D011239:Prednisolone; D009173:Mycophenolic Acid