Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mychophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation

Background. Our clinical trial was designed to investigate the optimal comb ination of immunosuppressants for renal transplantation. Methods. A randomized three-arm, parallel group, open label, prospective st udy was performed at 15 North American centers to compare three immunosuppr essive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neora l) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticos teroid regimen. Only patients with delayed graft function (32%) received an tilymphocyte induction. A total of 223 patients were randomized, transplant ed, and followed for 1 year. Results. There were no significant differences in baseline demography betwe en the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (c onfidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence int erval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant reje ction requiring antilymphocyte therapy was 12% in the tacrolimus + AZA grou p, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF grou p. There were no significant differences in overall patient or graft surviv al. Tacrolimus-treated patients had a lower incidence of hyperlipidemia thr ough 6 months posttransplant. The incidence of posttransplant diabetes mell itus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyc losporine + MMF and 7% in the tacrolimus + MMF groups. Conclusions, All regimens yielded similar acute rejection rates and graft s urvival, but the tacrolimus + MMF regimen was associated with the lowest ra te of steroid resistant rejection requiring antilymphocyte therapy.