Predictive value of tacrolimus concentration/dose ratio in first post-transplant week for CYP3A5-polymorphism in kidney-transplant recipients

• DOI: 10.5500/wjt.v15.i2.103247
• Publication Date: 2025-02-21T00:40:41Z
• Authors: 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

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.