Effect of delayed graft function on short- and long-term kidney graft survival.

Delayed graft function (DGF) has been identified as a predictor of poor long-term graft survival, but whether its effects are independent of rejection or final serum creatinine level is controversial. Based on the results of 57,025 first cadaver transplants reported to the UNOS Registry, we showed that: 1. Early acute rejection significantly lowered one-year graft survival rates by 8-9% in kidneys with early function (EF) (89% vs 80%; p < 0.001) or with DGF (72% vs 64%; p < 0.001). 2. DGF significantly lowered short- and long-term graft survival in patients without rejection (EF-1-yr graft survival rate of 89%, t1/2 of 9.5 years vs DGF-72% 1-yr graft survival rate, t1/2 of 6.7 years; p < 0.001). 3. Even when the discharge serum creatinine level was < 2.0 mg/dl with no rejection, DGF lowered graft survival (EF-1-yr graft survival rate of 93%, t1/2 of 10.4 years vs DGF-90% 1-yr graft survival rate, t1/2 of 7.6 years; p < 0.001). 4. Acute rejection, elevated discharge serum creatinine level (2-6 mg/dl) and older donor age (46-60 yrs) each lowered one-year graft survival rates in a stepwise fashion. There was exceptionally poor graft survival of kidneys from donors aged 46-60 with DGF, whether or not early acute rejection was present (with rejection-1-yr graft survival rate of 61%, t1/2 of 5.6 yrs vs no rejection-1-yr graft survival rate of 71%, t1/2 of 5.3 yrs). 5. Increasing cold ischemia time only decreased graft survival when there was no DGF and no rejection and had no significant effect on long-term graft survival. 6. Among recipients of HLA-matched cadaver kidneys, DGF lowered short- and long-term graft survival, even in the absence of early rejection (EF-1-yr graft survival rate of 93%, t1/2 of 14.8 yrs vs DGF-1-yr graft survival rate of 76%, t1/2 of 7.8 yrs). 7. DGF was associated with higher rates of acute rejection but impaired long-term graft survival even when rejection was absent and discharge creatinine was normal. These data support the hypothesis that DGF leads to an injury response that can reduce graft survival through antigen dependent and antigen independent mechanisms.