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Although donor and recipient risk factors for renal allograft failure are well known after kidney transplantation, they are less well defined after simultaneous pancreas-kidney transplantation. The purpose of this study is to evaluate the impact of donor and recipient risk factors on the outcome of the renal allograft in simultaneous pancreas-kidney recipients. Simultaneous pancreas-kidney transplant performed between 4/88 and 6/94 were reviewed (n=61) and univariate (Kaplan-Meier) and multivariate (Cox regression) analyses of factors which affect kidney graft survival were performed. Twelve donor and eleven pre- and post-transplant recipient risk factors were evaluated. Overall kidney allograft survival rates at 1, 2 and 5 yr were 81%, 76% and 66%. Donor age ≥40 yr (RR=2.3), donor female gender (RR=3.5), donor admission to pronouncement of brain death ≥48 h (RR=3), the occurrence of surgical complications (RR=2.1), and serum ≥2 mg/dl on post-transplant day (RR=1.9) were independently associated with an increased hazard of graft failure. With the exception of length of donor admission, all of these factors were also shown to predict the risk of renal graft failure by univariate analysis. In conclusion, we have identified donor and recipient risk factors which independently predict the risk of renal graft failure after simultaneous pancreas-kidney transplantation. Whether the differences between our center-specific risk factors and those obtained from renal transplant registry data are true differences or simply reflect sampling error is unclear.