Evaluation of CYP3A Phenoconversion in Immunosuppressed Patients Following Kidney Transplantation

Tacrolimus, featuring a narrow therapeutic index, is key in post-kidney transplant immunosuppression. Changes in CYP3A enzyme expression may complicate achieving therapeutic tacrolimus concentrations. This study investigated factors contributing to CYP3A phenoconversion.

Data from 24 kidney transplant recipients (May 2, 2021-November 27, 2024) were analyzed. CYP3A genotypes and phenotypes were assessed postoperatively before discharge, and re-evaluated after 2 (± 6 weeks; n = 14) or 3 years (± 6 weeks; n = 10). Changes in expression magnitude and metabolizer status between time points were analyzed regarding age, sex, time elapsed, and corticosteroid therapy.

Metabolizer status remained unchanged in 15 patients (7 in the 2-year, 8 in the 3-year group) and altered in 9 patients (7 in the 2-year, 2 in the 3-year group; 6 increased, 3 decreased). Status showed no significant association with age, sex, time, or mean corticosteroid dose. However, phenotype change demonstrated a significant association with time elapsed since surgery (P < .05).

Contrary to previous reports - likely due to our small sample size - administered corticosteroid therapy did not contribute to CYP3A phenoconversion. Aligned with international literature, time elapsed since transplantation appears to be an important factor associated with expression changes, potentially underpinned by the complex therapeutic regimen between measurements. Future studies with larger cohorts are planned.