1. The tacrolimus metabolism affect post‐transplant outcome mediating acute rejection and delayed graft function: analysis from Korean Organ Transplantation Registry data
- Author
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Myoung Soo Kim, Jin Min Kong, Ji Won Min, Tai Yeon Koo, Seung Sik Hwang, Joongyub Lee, Han Ro, Jong Cheol Jeong, Sung Kwang Park, Curie Ahn, and Jaeseok Yang
- Subjects
Graft Rejection ,medicine.medical_specialty ,Urology ,Delayed Graft Function ,Renal function ,030230 surgery ,Tacrolimus ,Organ transplantation ,03 medical and health sciences ,0302 clinical medicine ,Therapeutic index ,Republic of Korea ,medicine ,Humans ,Registries ,Kidney transplantation ,Transplantation ,business.industry ,Odds ratio ,medicine.disease ,Kidney Transplantation ,Confidence interval ,surgical procedures, operative ,030211 gastroenterology & hepatology ,business ,Immunosuppressive Agents - 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.
- Published
- 2020
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