AUTHOR=Javed Maryam , Sanghera Aruna , Khan Azhar Ali , Nagpal Ria , Butler Katie , Hobill Abigail , Gage Alice , Karst Felix , Needleman Amy , Hmun Mya , Thal Nicola , Shirling Graham , Fernando Ray , Jones Gareth , Harber Mark , Evans Rhys D. R. 

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

JOURNAL=Frontiers in Nephrology

VOLUME=Volume 5 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/nephrology/articles/10.3389/fneph.2025.1666191

DOI=10.3389/fneph.2025.1666191

ISSN=2813-0626

ABSTRACT=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.