Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Korea.
J Korean Med Sci. 2022 Feb 7;37(5):e33. doi: 10.3346/jkms.2022.37.e33.
Tacrolimus 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.
Trough(C) and 1.5-hour blood levels (C) of tacrolimus were measured in 95 kidney transplantation recipients. Patients with a C/C < 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.
Twenty-eight patients showed flat pattern peaks. The mean C/C 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 ( = 0.014). Patients having flat pattern peaks showed significantly lower post-transplant 36-month estimated glomerular filtration rate ( = 0.001). Two single nucleotide variants in ABCB1 genes, rs1922242 and rs2235035, were associated with flat pattern peaks ( = 0.019 and = 0.027, respectively).
Both of C and C should be measured to distinguish the patients showing unique initial absorption. A C/C ratio lower than 1.5 was associated with an increased risk of BPAR and/or borderline change. Single nucleotide variants s in gene might influence the flat pattern peaks of tacrolimus absorption.
他克莫司是实体器官移植中最常用的免疫抑制剂。在给予常规的每日两次剂量的他克莫司后，1.5 至 2 小时内达到峰值水平。一组肾移植患者在服用他克莫司后表现出不同的早期吸收相。
测量 95 例肾移植受者的他克莫司谷浓度（C）和 1.5 小时血药浓度（C）。C/C<1.5 和 C/C>1.5 的患者分别定义为具有平坦峰型和对照组。比较两组患者的移植结局。进行全外显子组测序以研究平坦峰型的遗传易感性。
28 例患者表现为平坦峰型。平坦峰型和对照组的平均 C/C 值分别为 1.13±0.22 和 3.78±1.25。多变量分析显示，平坦峰型是活检证实的急性排斥反应（BPAR）和/或边界变化的独立危险因素（=0.014）。具有平坦峰型的患者在移植后 36 个月的肾小球滤过率估计值明显降低（=0.001）。ABCB1 基因中的两个单核苷酸变异 rs1922242 和 rs2235035 与平坦峰型相关（=0.019 和=0.027）。
应同时测量 C 和 C 以区分具有独特初始吸收的患者。C/C 比值低于 1.5 与 BPAR 和/或边界变化的风险增加相关。基因中的单核苷酸变异可能影响他克莫司吸收的平坦峰型。
