A COMPARISON OF TACROLIMUS (FK506) AND CYCLOSPORINE FOR IMMUNOSUPPRESSION AFTER CADAVERIC RENAL-TRANSPLANTATION

Background. Tacrolimus (FK506), a macrolide molecule that potently inh ibits the expression of interleukin 2 by T lymphocytes, represents a p otential major advance in the management of rejection following solid- organ transplantation. This randomized, open-label study compared the efficacy and safety of tacrolimus-based versus cyclosporine-based immu nosuppression in patients receiving cadaveric kidney transplants. Meth ods. A total of 412 patients were randomized to tacrolimus (n=205) or cyclosporine (n=207) after cadaveric renal transplantation and were fo llowed for 1 year for patient and graft survival and the incidence of acute rejection. Results. One-year patient survival rates were 95.6% f or tacrolimus and 96.6% for cyclosporine (P=0.576). Corresponding 1-ye ar graft survival rates were 91.2% and 87.9% (P=0.289). There was a si gnificant reduction in the incidence of biopsy-confirmed acute rejecti on in the tacrolimus group (30.7%) compared with the cyclosporine grou p (46.4%, P=0.001), which was confirmed by blinded review, and in the use of antilymphocyte therapy for rejection (10.7% and 25.1%, respecti vely; P<0.001). Impaired renal function, gastrointestinal disorders, a nd neurological complications were commonly reported in both treatment groups, but tremor and paresthesia were more frequent in the tacrolim us group. The incidence of posttransplant diabetes mellitus was 19.9% in the tacrolimus group and 4.0% in the cyclosporine group (P<0.001), and was reversible in some patients. Conclusions. Tacrolimus is more e ffective than cyclosporine in preventing acute rejection in cadaveric renal allograft recipients, and significantly reduces the use of antil ymphocyte antibody preparations. Tacrolimus was associated with a high er incidence of neurologic events, which were rarely treatment limitin g, and with posttransplant diabetes mellitus, which was reversible in some patients.