Cyclosporin A used alone or in combination with low-dose steroids in cadaveric renal transplantation

The actual survival rate of 25 primary cadaveric kidney grafts in recipients treated initially with cyclosporin A (CyA) alone was 84%. The survival rate in 37 patients under conventional immunosuppression was 76%. The mean number of dialyses required in the first 4 weeks after transplantation was 1.2 per patient in both groups. At 15-28 months posttransplant, mean serum creatinine levels have remained stable at 175 mumol/l in the CyA group. The mean daily dose of steroids (including methylprednisolone i.v.) in the first two months was 2.07 mg/kg/d in patients under conventional immunosuppression and 0.76 mg/kg/d in the patients receiving CyA (p less than 0.001). The combination of CyA with low-dose steroids enabled the dose of CyA to be rapidly tapered off in once-weekly steps. CyA levels were monitored by determination of whole blood trough concentrations (target level: 300-800 ng/ml). At 60 days posttransplant the average dose of CyA was 6.0 +/- 0.5 mg/kg/d compared with an average daily dose of 11.4 +/- 0.9 as recommended for CyA alone in the protocol for the European multicentre study. This more rapid reduction in the CyA dose reduced nephrotoxicity (serum creatinine levels 174 +/- 14 as compared with 289 +/- 31 mumol/l) (p less than 0.05) and almost halved the number of methylprednisolone pulses given up to the end of the second month. We conclude from these results (1) that previously the dosage of CyA administered at this centre was probably too high, and (2) early adjustment of dose levels on the basis of blood concentrations and with low-dose prednisone cover appears to be safe and effective, but requires further verification.