Randomized study on the conversion of treatment with cyclosporine to azathioprine or mycophenolate mofetil followed by dose reduction

Background. The introduction of cyclosporine (CsA) in kidney transplantatio n has improved early graft survival. However, its long-term use is associat ed with impairment of renal function and increased cardiovascular risk, fac tors. To avoid CsA-related long-term adverse effects, patients were convert ed to either azathioprine (AZA) or mycophenolate mofetil (MMF) 1 year after transplantation. Methods. Between September 1995 and January 1997, 64 stable renal transplan t recipients on CsA and prednisone treatment were included in a prospective , randomized study. Patients were randomized for conversion of CsA to 2 mg/ kg AZA (n=30) or 1 g of MMF twice daily (n=34). All patients remained on lo w-dose steroids. To decrease the total immunosuppressive load, a dose reduc tion in MMF and AZA was performed at 4 and again at 8 months after conversi on. Mycophenolic acid trough levels were measured at regular intervals. Results. After conversion, a decrease in serum creatinine was found for bot h groups: for MMF, 132 to 109 mu mol/L (P=0.016); and for AZA, 123 to 112 m u mol/L (P<0.0001). After conversion, more acute rejections occurred in the AZA group (11/30) compared to the MMF group (4/34) (P=0.04), Dose reductio n of MMF to 500 mg twice daily and of AZA to 1.0 mg/kg elicited three rejec tions in both groups. The incidence of side effects and infections were sim ilar. Conclusion, Discontinuation of CsA spared renal function. In patients conve rted to MMF significantly less rejections occurred compared to patients con verted to AZA. Furthermore, dose reduction of both AZA and MMF is possible in the majority (72%) of the patients.