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조회309

민상일Sangil Min

서울대학교병원

Int. J. Surg., Jun 17 2024, | https://doi.org/10.1097/JS9.0000000000001800 Optimum tacrolimus trough levels for enhanced graft survival and safety in kidney transplantation: a retrospective multicenter real-world evidence study

Han, Ahram MD^a; Jo, Ae Jeong PhD^b; Kwon, Hyunwook MD, PhD^c; Kim, Young Hoon MD, PhD^c; Lee, Juhan MD^d; Huh, Kyu Ha MD, PhD^d; Lee, Kyo Won MD, PhD^e; Park, Jae Berm MD, PhD^e; Jang, Eunju MD^f; Park, Sun Cheol MD, PhD^f; Lee, Joongyub MD, PhD^g; Lee, Jeongyun^h; Kim, Younghye^h; Soliman, Mohamedⁱ; Min, Sangil MD, PhD^a,*

^aDivision of Transplantation and Vascular Surgery, Department of Surgery, Seoul National University Hospital, Seoul, South Korea

^bDepartment of Information Statistics, Andong National University, Andong, South Korea

^cDepartment of Kidney and Pancreases Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

^dDepartment of Surgery, Shinchon Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea

^eDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

^fDivision of Vascular and Transplant Surgery, Department of Surgery, College of Medicine, The Catholic University of Korea

^gDepartment of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea

^hMedical Affairs Department, Astellas Pharma Korea, South Korea

ⁱMedical Affairs Department, Astellas Pharma Singapore Pte Ltd., Singapore

^*Corresponding author : Sangil Min MD, PhD

Abstract

Background: The current study aimed to determine the optimal tacrolimus trough levels for balancing graft survival and patient safety following kidney transplantation.

Materials and methods: We conducted a retrospective cohort study involving 11,868 kidney transplant recipients from five medical centers. The association between tacrolimus exposures (periodic mean trough level, coefficient of variability, time in therapeutic range) and composite allograft outcome (de novo donor specific antibody, biopsy-proven rejection, kidney dysfunction, and graft failure), as well as safety outcomes (severe infection, cardiovascular events, malignancy, and mortality) were assessed. Data were sourced from Clinical Data Warehouses and analyzed using advanced statistical methods, including Cox marginal structural models with inverse probability treatment weighting.

Results: Tacrolimus levels of 5.0-7.9 ng/mL and 5.0-6.9 ng/mL during the 2-12 month and 12-72 month post-transplantation periods, respectively, were associated with reduced risks of composite allograft outcomes. During the first post-transplant year, the adjusted hazard ratios (aHR) for composite allograft outcomes were: 0.69 (95% CI 0.55-0.85, P<0.001) for 5.0-5.9 ng/mL; 0.81 (95% CI 0.67-0.98, P=0.033) for 6.0-6.9 ng/mL; and 0.73 (95% CI 0.60-0.89, P=0.002) for 7.0-7.9 ng/mL (compared to levels ≥8.0 ng/mL). For the 6-year composite outcomes, aHRs were 0.68 (95% CI 0.53-0.87, P=0.002) for 5.0-5.9 ng/mL and 0.65 (95% CI 0.50-0.85, P=0.001) for 6.0-6.9 ng/mL. These optimal ranges showed reduced rates of severe infection (6 y), malignancy (6 y), and mortality (1 y).

Conclusion: This multicenter study provides robust evidence for optimal tacrolimus trough levels during the periods 2-12 and 12-72 months following kidney transplantation.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-18)
연구진국내(교신)+국외 연구진
분야 의약학 > 면역의학

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