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In cadaveric renal transplantation, delayed graft function (DGF) correlates with poor long-term graft survival; however, whether its effects are independent of acute rejection is controversial. We wished to study the effect of DGF on graft survival, controlling for acute rejection, discharge creatinine, and human leukocyte antigen match.We analyzed 27,096 first cadaveric donor renal transplant report to the UNOS Scientific Renal Transplant Registry between January 1994 and November 1997. DGF was defined as dialysis need in the first week. Acute rejection was recorded for initial hospitalization and within 6 months. Kaplan Meier survival curves were analyzed with the log rank test.DGF increased the incidence of acute rejection before discharge (8% without DGF; 25% with DGF, P<0.01) and any acute rejections by 6 months (25% without DGF, 42% with DGF, P<0.01). Without early rejection, DGF reduced 1-year graft survival from 91 to 75% (P<0.0001) and graft half-time from 12.9 to 8.0 years. In kidneys with acute rejection within 6 months, DGF decreased 3-year graft survival from 77 to 60% and graft half-life from 9.4 to 6.2 years (P<0.001). With a discharge creatinine of less than 2.5 mg/dl, the difference in graft half-life between no DGF and no rejection (13.4 years) and DGF with rejection (9.8 years) was significant (P<0.001). Increased donor age and cold ischemia time additionally decreased graft survival, whereas a good human leukocyte antigen match could not overcome the deleterious effects of DGF or acute rejection.DGF is an important independent predictor of poor graft survival. Never immunosuppressive strategies must minimize nonimmune and immune renal injury if long-term graft survival is to improve.