Lee Soon Kyu, Choi Ho Joong, You Young Kyoung, Sung Pil Soo, Yoon Seung Kew, Jang Jeong Won, Choi Jong Young
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea.
The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea.
Clin Mol Hepatol. 2025 Jan;31(1):131-146. doi: 10.3350/cmh.2024.0451. Epub 2024 Oct 2.
BACKGROUND/AIMS: This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV).
Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified.
Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (p<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (p<0.05).
This study elucidated the optimal tacrolimus trough level and highlighted the impact of IPV on the CKD and ESRD development post-LT.
背景/目的：本研究旨在确定肝移植（LT）后慢性肾脏病（CKD）和终末期肾病（ESRD）的危险因素，特别关注他克莫司水平和患者内变异性（IPV）。
在2000年至2018年间接受LT的1076例患者中，952例纳入分析。每3个月记录他克莫司剂量和血药浓度，并使用变异系数计算IPV。根据LT时的基线肾功能计算CKD和ESRD的累积发病率。评估他克莫司水平及其IPV对CKD和ESRD发生发展的影响，并确定显著危险因素。
在中位随访97.3个月期间，急性肾损伤组CKD（0.58比0.24）和ESRD（0.07比0.01）的5年累积发病率显著高于正常肾小球滤过率（GFR）组。在正常GFR组中，他克莫司水平被确定为CKD的一个危险因素，建议血药浓度≤4.5 ng/mL可将CKD风险降至最低。此外，两组中他克莫司水平和剂量的IPV均成为CKD发生发展的显著危险因素（p<0.05），富马酸替诺福韦二吡呋酯也是乙肝感染患者的危险因素。他克莫司水平的IPV也是ESRD发生发展的显著因素（p<0.05）。
本研究阐明了他克莫司的最佳谷浓度，并强调了IPV对LT后CKD和ESRD发生发展的影响。
