MULTICENTER RANDOMIZED TRIAL COMPARING TACROLIMUS (FK506) AND CYCLOSPORINE IN THE PREVENTION OF RENAL-ALLOGRAFT REJECTION - A REPORT OF THEEUROPEAN TACROLIMUS-MULTICENTER-RENAL-STUDY-GROUP

Background. To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized tr ial compared the 12-month efficacy and safety of tacrolimus- and cyclo sporine-based immunosuppressive regimens in the prevention of renal al lograft rejection. Methods. A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug th erapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conj unction with azathioprine and low-dose corticosteroids. Results. At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25. 9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% co nfidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2 %; P=0.380) did not differ significantly between the two treatment gro ups. Overall, the safety profiles of the tacrolimus- and cyclosporine- based regimens were quite comparable. Infections, renal impairment, ne urological complications, and gastrointestinal complaints were frequen tly reported but were mostly reversible in both groups. Higher inciden ces of elevated serum creatinine, tremor, diarrhea, hyperglycemia, dia betes mellitus, and angina pectoris were reported in the tacrolimus tr eatment group, whereas acne, arrhythmia, gingival hyperplasia, and hir sutism were more frequent with cyclosporine treatment. Conclusions. Th e significant reduction in the incidence of episodes of allograft reje ction observed with tacrolimus therapy may have important long-term im plications given the prognostic influence of rejection on graft surviv al.