Relationship between eGFR Decline and Hard Outcomes after Kidney Transplants

Trials designed to assess the effect of interventions on death and graft failure in kidney transplant recipients are not feasible, because these are predominantly late events. Here, we examined the potential of percentage decline in eGFR as a surrogate for hard outcomes. We obtained deidentified data from the Australia and New Zealand Dialysis and Transplant Registry and studied 7949 transplants performed from 1995 to 2009, including 71,845 patient-years of follow-up, 1121 graft losses, and 1192 deaths. We used adjusted Cox proportional hazards models to determine risks of death or death-censored graft failure related to percentage change in eGFR between years 1 and 3 after transplant. Percentage change in eGFR was modeled as a restricted cubic spline. Rate of eGFR decline associated with exponentially increased risks of graft failure and death. Compared with stable eGFR, a >= 30% decline in eGFR, detected in 10% of patients, strongly associated with subsequent death (hazard ratio, 2.20; 95% confidence interval, 1.87 to 2.60) and death-censored graft failure (hazard ratio, 5.14; 95% confidence interval, 4.44 to 5.95). Decline in eGFR was superior to other surrogates, including acute rejection, doubling of serum creatinine level, and eGFR at year 1 or year 2. We conclude that 30% decline in eGFR between years 1 and 3 after kidney transplant is common and strongly associated with risks of subsequent death and death-censored graft failure, which mirrors findings in CKD. Percentage decline in eGFR should be considered for use as a surrogate outcome in kidney transplant trials.