Tacrolimus intrapatient variability and rejection are associated with inferior allograft outcomes after kidney transplantation

IntroductionEarly kidney transplant failure has significant negative impact for individuals and healthcare systems. Contemporary data investigating early allograft failure are lacking. We undertook a retrospective observational cohort study of adult patients who underwent kidney transplantation at a single European centre.MethodsWe determined causes of allograft failure between 1 and 5 years after transplant and explored clinical variables present at 1 year that predicted allograft loss.Results591 patients (median age 50 years, 64.1% male, and 44% white) were included; 531 (89.8%) had graft survival and 60 (10.2%) had graft loss between 1- and 5-years. Rejection was the primary cause of graft failure in 24 (40%) cases and 54% had undetectable tacrolimus levels prior to failure event. Female sex, serum creatinine at 1 year, the occurrence of rejection, and undetectable tacrolimus levels were associated with increased odds of graft loss. In subsequent analysis of 787 patients alive with a functioning graft at 1 year, recipient age, serum creatinine, proteinuria, any rejection episode, and tacrolimus intrapatient variability (IPV) at 1 yearwere associated with an increased hazard of graft loss.DiscussionHence, graft losses were predominantly alloimmune mediated, often associated with non-adherence, and were predicted by tacrolimus IPV at 1 year.