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. 2021 Jan;34(1):163-174.
doi: 10.1111/tri.13777. Epub 2020 Nov 9.

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

Han Ro  1 , Jong Cheol Jeong  2 , Jin Min Kong  3 , Ji Won Min  4 , Sung Kwang Park  5 , Joongyub Lee  6 , Tai Yeon Koo  7 , Jaeseok Yang  8 , Myoung Soo Kim  9 , Seungsik Hwang  10 , Curie Ahn  11
Affiliations
Free article

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

Han Ro et al. Transpl Int. 2021 Jan.
Free article

Abstract

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. The Korean Organ Transplantation Registry (KOTRY) datasets were used. A total of 3456 KT recipients were analyzed. The tacrolimus metabolism rate was defined as blood trough concentration of tacrolimus (C0 ) divided by the daily dose (D). 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 to -0.012, P = 0.044) and delayed graft function (DGF; NIE -0.119, 95% C.I. -0.231 to -0.007, P = 0.038). Slow tacrolimus metabolism was associated with better post-KT eGFR. AR and DGF were found to be significant mediators.

Keywords: kidney transplantation; pharmacogenetics; tacrolimus metabolism.

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