World journal of transplantation · 2025
Predictive value of tacrolimus concentration/dose ratio in first post-transplant week for CYP3A5-polymorphism in kidney-transplant recipients.
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Dung Pham-Thai, Su Hoang-Xuan, Tue Nguyen-Chi, Ben Nguyen-Huu, Phuong Nguyen-Minh, Tran Tuan-Ngoc, Nghia Phan-Ba, Van Diem-Thi, Dung Nguyen Thi-Thuy, Vinh Hoang-Trung, Rostaing Lionel, Toan Pham-Quoc
Аннотация
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.
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.