Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic syndrome

Abstract

We performed a multi-centre randomized controlled trial to compare the efficacy of mycophenolate mofetil (MMF) to that of cyclosporine A (CsA) in treating children with frequently relapsing nephrotic syndrome and biopsy-proven minimal change disease. Of the 31 randomized initially selected patients, seven were excluded. The remaining 24 children received either MMF 1200 mg/m(2) per day (n = 12) or CsA 4-5 mg/kg per day (n = 12) during a 12-month period. Of the 12 patients in the MMF group, two discontinued the study medication. Evaluation of the changes from the baseline glomerular filtration rate showed an overall significant difference in favour of MMF over the treatment period (p = 0.03). Seven of the 12 patients in the MMF group and 11 of the 12 patients in the CsA group remained in complete remission during the entire study period. Relapse rate in the MMF group was 0.83/year compared to 0.08/year in the CsA group (p = 0.08). None of the patients reported diarrhea. Pharmacokinetic profiles of mycophenolic acid were performed in seven patients. The patient with the lowest area under the curve had three relapses within 6 months. In children with frequently relapsing minimal change nephrotic syndrome, MMF has a favourable side effect profile compared to CsA; however, there is a tendency towards a higher relapse risk in patients treated with MMF.

Fig. 1

Flow chart of the study comparing mycophenolate mofetil (MMF) and cyclosporine (CsA) for remission maintenance in nephrotic syndrome. Asterisk indicates frequent relapses. There was one request for withdrawal from the study

Fig. 2

Change in the glomerular filtration rate (GFR) from baseline for patients receiving mycophenolate mofetil (MMF, n = 12) and cyclosporine A (CsA, n = 12) medication. The change in the GFR is expressed as ratio compared to baseline. Data are given as ANOVA estimates with standard errors. *p < 0.05 compared to baseline

Fig. 3

Relapse-free survival curve for patients with mycophenolate mofetil (MMF, n = 12) and cyclosporine A (CsA, n = 12) medication. The p value is from the logrank test

Fig. 4

Mycophenolic acid levels with area under the curve. Mycophenolic acid levels were measured using an immunoassay (filled symbols) or by high-performance liquid chromatography–ultraviolet test (open symbols). Unbroken line no relapses, broken line three relapses in 6 months