High-and Low-dose Regimens of Cyclosporin in Renal Transplantation: Immunosuppressive Efficacy and Side-effects

The immunosuppressive effectiveness and nephrotoxic side-effects of either high-dose cyclosporin (CsA) (16 mg/kg per day) or low-dose (9 mg/kg per day) in combination with azathioprine (Aza) (1 mg/kg per day) were studied in 80 renal transplant patients who also received low-dose corticosteroids. At 3 months, patients who received high-dose CsA were randomly assigned to either continuation of CsA or conversion to Aza, whereas in the triple-therapy group either CsA or Aza was discontinued. No differences in patient (97.5%) or graft survival (90%-92.5%) were found at 1 year. There were no differences in the incidence of primary non-functioning kidneys. The incidence of acute rejection episodes was 45% in the high-dose CsA group and 55% in the group treated with low CsA doses together with Aza (not significant). At 3 months the mean creatinine clearance was 60 +/- 4 ml/min (mean +/- SEM) in the high-dose group (mean cumulative CsA dose 0.96 g/kg) compared with 55 +/- 3 ml/min in the low-dose group (mean cumulative CsA dose 0.60 g/kg). At 1 year no differences in the degree of proteinuria or the incidence of hypertension was found between the different groups. The best mean creatinine clearance at 1 year (77 +/- 5 ml/min) was found in patients who received high doses of CsA for 3 months followed by conversion.