Insight Into The Potential Influence Of Inter- And Intra-Individual Variability Of Tacrolimus Exposure On Graft Function Decline In Three-Year Period Following Kidney Transplantation

The main goal of the present study was to evaluate the association of tacrolimus (Tac) exposure parameters (trough concentration (TTC), dose-adjusted TTC (C-0/D)), Tac intra-individual variability (IPV), and Tac-related gene polymorphisms (CYP3A5 and ABCB1) with kidney function in three-year period after kidney transplantation (Tx). The study enrolled 103 Caucasian patients who were genotyped on CYP3A5 6986A>G and ABCB1 3435C>T polymorphism. High IPV, lower average C-0/D, kidney function at 6 months post-transplantation, and acute rejection were independent predictors of worse eGFR values between 13 and 36 months after Tx. Significant eGFR decline was observed in the low C-0/D (p = 0.010) and high IPV patients' group (p = 0.018) between 13 - 24 and 25 - 36 months. The carriers of CYP3A5*1 allele had lower C-0/D values compared to the CYP3A5*3/*3 carriers during entire observation period, while ABCB1 3435 gene polymorphism did not affect C-0/D. Tailoring Tac treatment based on IPV, C-0/D and CYP3A5 genotype in clinical practice may identify patients at risk for graft function decline.