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

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.

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.

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).

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.