Late graft failure after kidney transplantation as the consequence of late versus early events

Beyond the first posttransplant year, 3% of kidney transplants fail annually. In a prospective, multicenter cohort study, we tested the relative impact of early versus late events on risk of long-term death-censored graft failure (DCGF). In grafts surviving at least 90 days, early events (acute rejection [AR] and delayed graft function [DGF] before day 90) were recorded; serum creatinine (Cr) at day 90 was defined as baseline. Thereafter, a 25% rise in serum Cr or new onset proteinuria triggered graft biopsy (index biopsy, IBx), allowing comparison of risk of DCGF associated with early events (AR, DGF, baseline serum Cr >2.0 mg/dL) to that associated with later events (IBx). Among 3678 patients followed 4.7±1.9 years, 753(20%) had IBx at a median of 15.3 months posttransplant. Early AR (HR=1.77, p<0.001) and elevated Cr at Day 90 (HR=2.56, p<0.0001) associated with increased risk of DCGF; however, later-onset dysfunction requiring IBx had far greater impact (HR=13.8, p<0.0001). At 90 days, neither clinical characteristics nor early events distinguished those who subsequently did or did not undergo IBx or suffer DCGF. To improve long-term kidney allograft survival, management paradigms should promote prompt diagnosis and treatment of both early and later events. This article is protected by copyright. All rights reserved.