Introduction: The cytochrome P450 3A5 (CYP3A5) gene polymorphisms are known to influence tacrolimus pharmacokinetics. However, conflicting study results exist regarding the association between genotype and tacrolimus-related nephrotoxicity. This study aimed to assess the impact of CYP3A5 gene polymorphisms on renal function in Asian heart transplant recipients receiving a tacrolimus-based immunosuppressant regimen.
Method: This retrospective cohort study included heart transplant recipients from a medical center in Taiwan. Patients aged over 18 years who underwent their first heart transplantation and provided informed consent were eligible for inclusion. Patients who required dialysis at the time of discharge after transplant surgery were excluded. Participants were categorized into two groups based on their CYP3A5 genotype: extensive metabolizer (EM) group for CYP3A5*1 carriers (CYP3A5*1/*1 and CYP3A5*1/*3) and poor metabolizer (PM) group for non-carriers (CYP3A5*3/*3). Data collection included tacrolimus dosages and serum concentrations, as well as renal function assessments at baseline, discharge from transplant surgery, and every three months post-discharge for up to five years post-transplant. Changes in estimated glomerular filtration rate (eGFR) and incidents of renal function deterioration (defined as a decline of >40% in eGFR or eGFR <15 mL/min/1.73 m²) were compared between the two groups.
Results: A total of 35 patients were included, with a mean age of 54.4±8.7 years, of whom 34 (97.1%) were male, and the mean follow-up time was 5.3±3.2 years. Of these, 16 patients (45.7%) were in the EM group, including six (17.1%) with CYP3A5*1/*1 and ten (28.6%) with CYP3A5*1/*3 genotypes. The remaining 19 patients (54.3%) with CYP3A5*3/*3 genotype were in the PM group. Although there were no significant differences in serum tacrolimus concentrations between the two groups throughout the cohort period, the mean tacrolimus concentration/dose ratio was significantly higher in the PM group compared to the EM group (4.15±0.49 vs. 1.36±0.18 ng/mL per mg/day, P<0.001). The eGFR at discharge was 89.4±36.4 and 93.4±58.0 mL/min/1.73 m² in the EM and PM groups, respectively (P=0.91). Changes in eGFR from discharge over the cohort period did not show significant differences between the EM and PM groups (annual decline rate at 5 years post-transplant: 4.5±3.5 vs. 5.1±9.7 mL/min/1.73 m², P=0.35). Seven patients in each group experienced renal function deterioration events (43.8% vs. 36.8%, P=0.74).
Conclusion: This study did not find an association between CYP3A5 gene polymorphisms and renal function in Asian heart transplant recipients receiving tacrolimus-based immunosuppressant regimen.