The tacrolimus metabolism affect post-transplant outcome mediating acute rejection and delayed graft function: analysis from Korean Organ Transplantation Registry (KOTRY) data

Han Ro, Jong Cheol Jeong, Jin Min Kong, Ji Won Min, Sung Kwang Park, Joongyub Lee, Tai Yeon Koo, Jaeseok Yang, Myoung Soo Kim, Seungsik Hwang, Curie Ahn
Transplant International 2020 October 24

BACKGROUND: Tacrolimus is a key drug in kidney transplantation (KT) with a narrow therapeutic index. The association between the tacrolimus metabolism rate and KT outcomes have not been investigated in large-scale multi-center studies.

METHODS: The Korean Organ Transplantation Registry (KOTRY) datasets were used. A total of 3,456 KT recipients were analyzed. The tacrolimus metabolism rate was defined as blood trough concentration of tacrolimus (C0 ) divided by the daily dose (D).

RESULTS: The patients were grouped into fast, intermediate, or slow metabolizers by the C0 /D measured 6 months after transplantation. The slow metabolism group was associated with a 2.7 ml/min/1.73 m2 higher adjusted estimated glomerular filtration rate (eGFR) at 6 months (95% confidence interval (C.I.) 1.2-4.3, p=0.001), less acute rejection (AR) within 6 months (Odds ratio (OR) 0.744, 95% C.I. 0.585-0.947, p=0.016), and less interstitial fibrosis and tubular atrophy (OR 0.606, 95% C.I. 0.390-0.940, p=0.025). Fast tacrolimus metabolism affected the 6-month post-KT eGFR through mediation of AR (natural indirect effect (NIE) -0.434, 95% C.I. -0.856--0.012, p=0.044) and delayed graft function (DGF) (NIE -0.119, 95% C.I. -0.231--0.007, p=0.038).

CONCLUSIONS: Slow tacrolimus metabolism was associated with better post-KT eGFR. AR and DGF were found to be significant mediators.

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