Interaction of mycophenolate mofetil and HLA matching on renal allograft survival

Introduction. The importance of HLA matching for renal transplantation outc omes has been appreciated for several decades, It has been hypothesized tha t as pharmacologic immunosuppression becomes stronger and more specific, th e impact of HLA matching may be vanishing. Mycophenolate Mofetil (MMF) has been demonstrated to both decrease acute rejection and improve three-year g raft survival. It is possible that with new immunosuppressive regimens cont aining MMF the relative effect of HLA matching may be altered. To determine the relative impact of HLA matching in patients on MMF we undertook an ana lysis of the United States Renal Transplant Data Registry (USRDS). Methods. All primary, solitary renal transplants registered at the USRDS be tween January 1995 and June 1997, on initial immunosuppression that include d either MMF or AZA were followed until June 1998. Primary study end points were graft and patient survival. Kaplan-Meier analysis was performed to co mpare AZA vs. MMF treated patients by HLA mismatch, Cox proportional hazard models were used to investigate the interaction between HLA mismatch and A ZA versus MMF therapy on the study endpoints, All multivariate analyses wer e corrected for 13 potential confounding pretransplant variables including intention to treat immunosuppression. Results. A total of 19,675 patients were analyzed (8,459 on MMF and 11,216 on AZA), Overall three year graft survival was higher in the MMF group when compared to the AZA group (87% vs. 84% respectively P<0.001). For both AZA and MMF three-year graft survival improved with fewer HLA donor-recipient mismatches, Comparing zero antigen mismatches to six antigen mismatches, th e relative improvement was comparable for both patients on AZA (92.4% vs. 8 0.6%) and MMF (95.2% vs. 82.9%), By Cox proportional hazard model the relat ive risk. for graft loss decreased significantly in both the AZA and MMF tr eated patients with increased HLA matching. Conclusion, The use of MMF does not obviate the benefits of HLA matching, w hile HLA matching does not minimize the benefits of MMF on long term graft survival, Our study would suggest that HLA matching and;MMF therapy are add itive factors in decreasing the risk for renal allograft loss.