• Suh Min Kim, Younggyun Lim, Sangil Min, Byung-Joo Min, Myung-Eui Seo, Kye Hwa Lee, Ju Han Kim, and Jongwon Ha.
• Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
• J. Korean Med. Sci. 2022 Feb 7; 37 (5): e33.

BackgroundTacrolimus is the most commonly used immunosuppressive drug in solid organ transplantation. After administering a conventional twice-daily dose of tacrolimus, peak levels were achieved within the first 1.5 to 2 hours. A group of patients showed different early absorption phase of tacrolimus after kidney transplantation.MethodsTrough(C0) and 1.5-hour blood levels (C1.5) of tacrolimus were measured in 95 kidney transplantation recipients. Patients with a C1.5/C0 < 1.5 and > 1.5 were defined as those having flat pattern peaks and as controls, respectively. Transplantation outcomes were compared between the groups. Whole exome sequencing was performed to investigate the genetic susceptibility to flat pattern peaks.ResultsTwenty-eight patients showed flat pattern peaks. The mean C1.5/C0 values were 1.13 ± 0.22 and 3.78 ± 1.25 in the flat pattern peak and control groups, respectively. In multivariate analysis, flat pattern peak was an independent risk factor for biopsy-proven acute rejection (BPAR) and/or borderline change (P = 0.014). Patients having flat pattern peaks showed significantly lower post-transplant 36-month estimated glomerular filtration rate (P = 0.001). Two single nucleotide variants in ABCB1 genes, rs1922242 and rs2235035, were associated with flat pattern peaks (P = 0.019 and P = 0.027, respectively).ConclusionBoth of C1.5 and C0 should be measured to distinguish the patients showing unique initial absorption. A C1.5/C0 ratio lower than 1.5 was associated with an increased risk of BPAR and/or borderline change. Single nucleotide variants s in ABCB1 gene might influence the flat pattern peaks of tacrolimus absorption.© 2022 The Korean Academy of Medical Sciences.

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