Five-year study of tacrolimus as secondary intervention versus continuation of cyclosporine in renal transplant patients at risk for chronic renal allograft failure.

ABSTRACT

BACKGROUND: Chronic allograft nephropathy is the most frequent cause of long-term kidney allograft loss. Studies are desperately needed to improve long-term survival. Tacrolimus has been associated with less rejection and better kidney function compared with cyclosporine in clinical trials. This study tested the hypothesis that conversion from cyclosporine to tacrolimus might improve long-term outcomes in patients with chronic allograft damage. METHODS: In this multicenter Canadian clinical trial, cyclosporine-treated patients with biopsy-proven chronic allograft nephropathy and impaired renal function were randomly assigned (21) to convert to tacrolimus or continue on cyclosporine therapy. A total of 106 (70 tacrolimus and 36 cyclosporine treated) patients were followed-up for up to 5 years. The primary outcome was graft survival. RESULTS: In an intention to treat analysis, subsequent graft (73% vs. 81%, P=0.2835, log-rank test) and patient survival (91% vs. 92%, P=0.8668, log-rank test) were not different between the tacrolimus and cyclosporine groups, respectively. Changes in Chronic Allograft Damage Index scores on protocol biopsies from baseline to 3 years were not different (+0.4+/-1.8 vs. +1.3+/-3.2, P=0.5910, cyclosporine vs. tacrolimus, respectively). There were no significant differences in biopsy-proven acute rejection (6 [8.6%] vs. 2 [5.6%], tacrolimus vs. cyclosporine, respectively, P=0.5906). CONCLUSIONS: In this study, patients with chronic allograft damage converted from cyclosporine to tacrolimus demonstrated no apparent benefit.