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

Publication Type
Journal Article
Year of Publication
Johnson, C; Ahsan, N; Gonwa, T; Halloran, P; Stegall, M; Hardy, M; Metzger, R; Shield, C; Rocher, L; Scandling, J; Sorensen, J; Mulloy, L; Light, J; Corwin, C; Danovitch, G; Wachs, M; Van Veldhuisen, P; Salm, K; Tolzman, D; Fitzsimmons, W E
Date Published
2000 Mar 15
Adult; Azathioprine; Cadaver; Cyclosporine; Drug Therapy, Combination; Female; Graft Survival; Humans; Immunosuppressive Agents; kidney transplantation; Male; Middle Aged; Mycophenolic Acid; Postoperative Care; Prospective Studies; Tacrolimus

BACKGROUND: Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation.

METHODS: A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year.

RESULTS: There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups.

CONCLUSIONS: All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.