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.
McDonald
Stephen P
SP
ANZDATA Registry, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia. stephenm@anzdata.org.au
Russ
Graeme R
GR
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D015331:Cohort Studies; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D004110:Diltiazem / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015994:Incidence; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation; D016016:Proportional Hazards Models; D012042:Registries; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D004110:Diltiazem