The tacrolimus metabolism affect post-transplant outcome mediating acute rejection and delayed graft function: analysis from Korean Organ Transplantation Registry data
- Authors
- Ro, Han; Jeong, Jong Cheol; Kong, Jin Min; Min, Ji Won; Park, Sung Kwang; Lee, Joongyub; Koo, Tai Yeon; Yang, Jaeseok; Kim, Myoung Soo; Hwang, Seungsik; Ahn, Curie
- Issue Date
- Jan-2021
- Publisher
- WILEY
- Keywords
- kidney transplantation; pharmacogenetics; tacrolimus metabolism
- Citation
- TRANSPLANT INTERNATIONAL, v.34, no.1, pp.163 - 174
- Journal Title
- TRANSPLANT INTERNATIONAL
- Volume
- 34
- Number
- 1
- Start Page
- 163
- End Page
- 174
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/79779
- DOI
- 10.1111/tri.13777
- ISSN
- 0934-0874
- 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 (C-0) divided by the daily dose (D). The patients were grouped into fast, intermediate, or slow metabolizers by the C-0/D measured 6 months after transplantation. The slow metabolism group was associated with a 2.7 ml/min/1.73 m(2) 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.
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