Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years.

Publication Type
Journal Article
Year of Publication
Ahsan, N; Johnson, C; 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; VanVeldhuisen, P; Salm, K; Tolzman, D; Fitzsimmons, W E
Date Published
2001 Jul 27
Administration, Oral; Adolescent; Adult; African Continental Ancestry Group; Antilymphocyte Serum; Azathioprine; Cadaver; Child; Cross-Over Studies; Cyclosporine; diabetes mellitus; Drug Monitoring; Drug Therapy, Combination; European Continental Ancestry Group; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Insulin; Kidney Function Tests; kidney transplantation; Kidney Tubular Necrosis, Acute; Mycophenolic Acid; Postoperative Complications; Survival Rate; Tacrolimus; Time Factors; Tissue Donors; United States

BACKGROUND: A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years.

METHODS: Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years.

RESULTS: The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P=0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF.

CONCLUSIONS: All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.