Effect of adding Mycophenolate mofetil in paediatric renal transplant recipients with chronical cyclosporine nephrotoxicity

Abstract: Cyclosporine (CyA) has made a great impact on 1-year allograft survival, however, after years, renal function deteriorates, possibly due to chronic toxicity. Recently, Mycophenolate mofetil (MMF) was introduced as a non-nephrotoxic immunosuppressant that might be effective in chronical transplant arteriolopathy. We therefore started MMF at a dose of 600 mg/m² b. i. d. in 18 pediatric renal transplant recipients (10.8 ± 3.9 (SD) years of age at transplantation, 11/18 with a history of rejections) with biopsy-proven chronic arteriolopathy and other signs of CyA toxicity at a mean follow up time of 6.2 ± 2.7 (range 2.3–11.8) years after transplantation. One month prior to conversion, mean serum creatinine was 171 ± 96 μmol/l, lower than at the time of conversion (188 ± 100 μmol/l, P = 0.003, paired t-test). At last follow-up (median 13.7 months, range 5.0 to 25.0 months) after conversion, mean serum creatinine decreased significantly to 127 ± 69 μmol/l (P = 0,0003, paired t-test). The CyA dosage was reduced from a mean of 150 ± 39 mg/m2 per day to 59 ± 13 mg/m² per day in 7 patients, and CyA was discontinued in 11 patients after a median period of nine months (range 1–18 months). After a median period of 21 days, a pharmacokinetic profile was performed in all patients. The mean MMF dose was 1117 ± 319 mg/m² per day (range 675–1774 mg/m² per day). The mean Mycophenolic acid (MPA) trough concentration was 4.0 ± 2.0 μg/ml, range 1.4–7.9 μg/ml. Mean 12 h MPA AUC was 70.6 ± 28.1 (range 31.9–127) μg × h/ml. Except for one patient with diarrhea associated with a high AUC, and for one patient with a steroid-sensitive rejection episode after 566 days, no other patient experienced side effects or a rejection episode. Prednisolone was left unaltered at 2–4 mg/m² per day. We conclude that MMF allows safe reduction of CyA with markedly better graft function, suggesting that chronical CyA-toxicity partially accounts for deteriorating allograft function.