Associations between use of cyclosporine-sparing agents and outcome in kidney transplant recipients

BACKGROUND: Diltiazem, widely used as a cyclosporine-sparing agent, has been suggested to confer a benefit on graft and patient outcome in kidney transplantation related to immunomodulatory properties. Use of cyclosporine-sparing agents (CsSpA) is routinely recorded by the Australia & New Zealand Dialysis and Transplant (ANZDATA) Registry, and we used these data to examine the associations between CsSpA use and outcomes. METHODS: Graft and patient survival were analyzed for a cohort of 3913 people who received kidney transplants in Australia or New Zealand between 1 April 1993 and 30 March 2001. Patients were followed to death or loss of graft function. Graft and patient survival analyses were performed using Cox proportional hazards models, including a time varying covariate for CsSpA use in analyses of graft failure. Occurrence of delayed graft function (DGF) and acute rejection also were examined as secondary outcomes. RESULTS: There was no difference in patient survival in the first 12 months post transplantation, but from 12 months onwards there is a survival advantage associated with CsSpA use among cadaveric donor (CD) recipients in both univariate hazard ratio (HR) 0.56, 95% CI 0.41 to 0.76, P < 0.001 and multivariate (HR 0.56, 95% CI 0.40 to 0.79, P < 0.001) analyses. This was consistent across subgroups examined. Lower rates of early graft loss (censored for death) were associated with CsSpA use odds ratio (OR) 0.61, 95% CI 0.50 to 0.75, P < 0.0001]. Lower rates of use of antibody therapy for rejection also were observed, but not lower rates of biopsy-proven rejection. CONCLUSIONS: CsSpA use was associated with improved patient mortality after kidney transplantation. Whether this was a direct drug effect or due to other factors associated with diltiazem use cannot be inferred directly from these data, although several plausible mechanisms exist which might mediate a diltiazem effect.