Initial Kidney Graft Function and Its Association With Short- and Long-term Graft Outcomes: A Paired Kidney Analysis

BACKGROUND: Achieving optimal initial graft function depends on the complex interplay between donor quality, ischemia-reperfusion injury, and recipient characteristics. Delayed graft function (DGF) is commonly used as a trial endpoint, yet its validity as a surrogate for long-term graft survival remains uncertain. METHODS: Using data from the Australia and New Zealand Dialysis and Transplant Registry (2000-2023), we analyzed 3256 kidney transplant recipients from 1628 paired donors to compare death-censored graft loss (DCGL) and all-cause graft loss (ACGL) across immediate graft function (IGF), slow graft function (SGF), and DGF groups. A paired donor kidney design was used to control for donor-related factors, and Cox proportional hazards models with stepwise time-varying coefficients were fitted to account for nonproportional hazards. RESULTS: Over a median follow-up of 5.5 y (interquartile range, 2.4-9.7 y), recipients with DGF (n = 832 per group) experienced a higher risk of both DCGL and ACGL during the first 6 mo posttransplant compared with those with IGF (adjusted hazard ratio [95% confidence interval], 3.37 [1.43-7.96] and 1.97 [1.09-3.56], respectively). No associations were observed between 6 and 12 mo. Beyond 12 mo, an attenuated association persisted only for ACGL (adjusted hazard ratio, 1.35 [1.05-1.72]), with no corresponding association for DCGL. No significant differences in graft loss were observed between SGF and DGF (n = 378 per group) or between IGF and SGF (n = 418 per group). CONCLUSIONS: These findings indicate that graft loss associated with DGF, independent of donor characteristics, is limited to the early posttransplant period. Future trials should therefore be cautious in adopting DGF as a primary surrogate endpoint for medium- and long-term graft survival.