Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Predictive value of tacrolimus concentration/dose ratio in first post-transplant week for CYP3A5-polymorphism in kidney-transplant recipients
Pham-Thai Dung, Hoang-Xuan Su, Nguyen-Chi Tue, Nguyen-Huu Ben, Nguyen-Minh Phuong, Tuan-Ngoc Tran, Phan-Ba Nghia, Diem-Thi Van, Nguyen Thi-Thuy Dung, Hoang-Trung Vinh, Lionel Rostaing, Pham-Quoc Toan
Pham-Thai Dung, Center of Critical Care Medicine, Emergency and Clinical Toxicology, Military Hospital, Hanoï 100000, Viet Nam
Hoang-Xuan Su, Institute of Biomedicine and Pharmacy, Vietnam Military Medical University, Hanoï 100000, Viet Nam
Nguyen-Chi Tue, Department of Post-Transplant Intensive Care and Treatment, Center of Organ Transplantation - Military Hospital, Hanoï 100000, Viet Nam
Nguyen-Huu Ben, Nguyen-Minh Phuong, Department of Occupational Medicine, Vietnam Military Medical University, Hanoï 100000, Viet Nam
Tuan-Ngoc Tran, Department of Military Medical Command and Organization, Vietnam Military Medical University, Hanoï 100000, Viet Nam
Phan-Ba Nghia, Diem-Thi Van, Nguyen Thi-Thuy Dung, Hoang-Trung Vinh, Lionel Rostaing, Pham-Quoc Toan, Department of Nephrology and Dialysis, Military Hospital, Hanoï 100000, Viet Nam
Lionel Rostaing, Department of Nephrology, Hemodialysis, Apheresis, and Kidney Transplantation, Grenoble University Hospital, Grenoble 38043, Auvergne-Rhone-Alpes, France
Author contributions: Dung PT contributed to the formal analysis of the manuscript and wrote the original manuscript preparation; Su HX contributed to the resources of the manuscript; Toan PQ conceptualized the manuscript; Ben NH applied the software; Phuong NM validated the manuscript; Rostaing L contributed to the supervision of the manuscript; Toan PQ performed the project management and the acquisition of funds; Dung PT and Su HX for methodology; Dung PT, Toan PQ, and Su HX for survey; Tue NC, Nghia PB, Van DT, Dung NTT, Tue NC, Nghia PB, Van DT, and Dung NTT for data organization of the manuscript; Toan PQ, and Rostaing L wrote, reviewed, and edited the manuscript; Vinh HT and Tran TN visualized; and all authors thoroughly reviewed and endorsed the final manuscript.
Supported by the Vietnam National Foundation for Science and Technology Development, No. NAFOSTED 04/2020/TN.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam, approval No. November 25th, 2022).
Informed consent statement: The informed consent was waived by the Institutional Review Board.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement:
Data are available upon reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Lionel Rostaing, MD, PhD, Professor, Department of Nephrology and Dialysis, Military Hospital, Phung Hung Street, Hanoï 100000, Viet Nam.
lrostaing@chu-grenoble.fr
Received: November 15, 2024
Revised: December 17, 2024
Accepted: January 2, 2025
Published online: June 18, 2025
Processing time: 98 Days and 18.6 Hours
BACKGROUND
Tacrolimus (TAC) is metabolized primarily by the CYP3A-encoded enzyme family (CYP3A4, CYP3A5, and CYP3A7). Individuals expressing the CYP3A51 allele are considered fast metabolizers and generally require higher TAC doses to reach therapeutic levels.
AIM
To evaluate the predictive value of the TAC concentration-to-dose (C0/D) ratio for identifying CYP3A5 polymorphisms in renal transplant recipients.
METHODS
Eighty-six de novo kidney transplant recipients with TAC-based immunosuppression from the Department of Nephrology and Dialysis at Military Hospital 103 (Hanoi, Vietnam) were included in this retrospective study. Blood samples were collected within the first week post-transplantation to monitor TAC levels and to perform genotyping for CYP3A5 genetic polymorphisms.
RESULTS
The CYP3A53/3 genotype was identified in 37 patients (43%), CYP3A51/3 in 40 patients (46.5%), and CYP3A51/1 in 9 patients (10.5%). Patients carrying the CYP3A51/3 or CYP3A51/1 genotype, classified as fast metabolizers (CYP3A5 expressers), had significantly lower TAC C0 concentrations and C0/D ratios compared to slow metabolizers (CYP3A53/3 genotype) at multiple time points during follow-up (all P < 0.001). Notably, the TAC C0/D ratio obtained on day 1 (0.91) was shown to predict CYP3A5 polymorphism with a sensitivity of 84.6% and a specificity of 84.6%.
CONCLUSION
This study demonstrates that the TAC C0/D ratio provides a reliable predictive value for CYP3A5 polymorphisms, which can be used to individualize TAC dosing in renal transplant recipients in Vietnam and other low-income countries.
Core Tip: We included in this single-center retrospective study 86 de novo kidney transplant recipients with tacrolimus (TAC)-based immunosuppression. This study aims to evaluate the predictive value of the TAC concentration-to-dose (C0/D) ratio for identifying CYP3A5 polymorphisms within the first week after kidney transplantation. We found that the TAC C0/D ratio provides a reliable predictive value for CYP3A5 polymorphisms, which can be used to individualize TAC dosing in kidney transplant recipients in low-income countries.
