Interaction of mycophenolate mofetil and HLA matching on renal allograft survival.
BACKGROUND
The importance of HLA matching for renal transplantation outcomes has been appreciated for several decades. It has been hypothesized that as pharmacologic immunosuppression becomes stronger and more specific, the impact of HLA matching may be vanishing. Mycophenolate Mofetil (MMF) has been demonstrated to both decrease acute rejection and improve three-year graft survival. It is possible that with new immunosuppressive regimens containing 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 analysis of the United States Renal Transplant Data Registry (USRDS).


METHODS
All primary, solitary renal transplants registered at the USRDS between January 1995 and June 1997, on initial immunosuppression that included either MMF or AZA were followed until June 1998. Primary study end points were graft and patient survival. Kaplan-Meier analysis was performed to compare AZA vs. MMF treated patients by HLA mismatch. Cox proportional hazard models were used to investigate the interaction between HLA mismatch and AZA versus MMF therapy on the study endpoints. All multivariate analyses were 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, the relative improvement was comparable for both patients on AZA (92.4% vs. 80.6%) and MMF (95.2% vs. 82.9%). By Cox proportional hazard model the relative risk for graft loss decreased significantly in both the AZA and MMF treated patients with increased HLA matching.


CONCLUSIONS
The use of MMF does not obviate the benefits of HLA matching, while 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 additive factors in decreasing the risk for renal allograft loss.
Meier-Kriesche
H U
HU
Department of Medicine, The University of Michigan, Ann Arbor 48109-0364, USA.
Ojo
A O
AO
Leichtman
A B
AB
Magee
J C
JC
Rudich
S M
SM
Hanson
J A
JA
Cibrik
D M
DM
Kaplan
B
B
D001379:Azathioprine / Q000627:therapeutic use; D015331:Cohort Studies; D004347:Drug Interactions; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D015234:HLA-A Antigens / Q000276:immunology / Q000494:pharmacology*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D014184:Transplantation, Homologous
D015234:HLA-A Antigens; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine