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

Maryam Javed¹Aruna Sanghera²Azhar Ali Khan¹Ria Nagpal¹Katie Butler³Abigail Hobill¹Alice Gage^1,2Felix Karst¹Amy Needleman¹Mya Hmun^1,2Nicola Thal³Graham Shirling³Raymond Fernando^2,3Gareth Jones^1,2Mark Harber^1,2Rhys Evans^1,2*

• ¹Royal Free NHS Foundation Trust, London, United Kingdom
• ²University College London, London, United Kingdom
• ³Anthony Nolan Histocompatibility Laboratories, London, United Kingdom

Early 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. We determined causes of allograft failure between 1 and 5 years after transplant and explored clinical variables present at 1 year that predicted allograft loss. 591 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 year were associated with an increased hazard of graft loss. Hence, graft losses were predominantly alloimmune mediated, often associated with non-adherence, and were predicted by tacrolimus IPV at 1 year.