Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation |
Soon Kyu Lee1,2, Ho Joong Choi3, Young Kyoung You3, Pil Soo Sung2,4, Seung Kew Yoon2,4, Jeong Won Jang2,4, Jong Young Choi2,4 |
1Division of gastroenterology and hepatology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea 2The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea, Seoul, Republic of Korea 3Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea 4Division of gastroenterology and hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea |
Correspondence : |
Jong Young Choi , Tel: +82-2-2258-2073, Fax: +82-2-599-3589, Email: jychoi@catholic.ac.kr |
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Received: June 14, 2024 Revised: September 13, 2024 Accepted: September 29, 2024 |
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ABSTRACT |
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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).
Methods 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.
Results 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 (AKI) 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).
Conclusions This study elucidated the optimal tacrolimus through level and highlighted the impact of IPV on the CKD and ESRD development post-LT. |
KeyWords:
Liver transplantation, chronic kidney disease, end-stage renal disease, tacrolimus, tenofovir, diabetes mellitus |
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