Akademik Veri Yönetim Sistemi
27. Ulusal, 2. Uluslararası Farmakoloji Kongresi, Antalya, Türkiye, 23 - 26 Kasım 2023, ss.320-321
Objectives: Tacrolimus(TAC, FK-506) is a calcineurin inhibitor and commonly used as an immunosuppressive agent for the prevention organ rejection in organ transplant patients. TAC is an immunosuppressive agent with narrow therapeutic index and nephrotoxic effects, characterized by interindividual dose variability. Calcineurin inhibitor toxicity(CNIT) is characterized by renal dysfunction and increased serum creatinine values. TAC is metabolized by the CYP450(CYP3A5) and transported by P-glycoprotein(ABCB1). CYP2C8 enzyme plays protective role against organ rejection and toxicity. In our study, we aimed to investigate the effect of gene polymorphisms on kidney function in patients using Tac.
Material-Methods: 105 kidney transplant patients aged 18-65 years using TAC were included in the study. As a result of genetic typing, CYP3A5(6986A>G), ABCB(3435C>T) and CYP2C8(A1196G) polymorphisms were determined by allele-specific polymerase chain reaction. At 3, 6, and 12 months post-transplant daily TAC dose(mg/kg), concentration(ng/mL) and to evaluate kidney function creatinine(mg/dL), GFR(mL/min/1.73 m²) and urine protein/creatinine levels were determined retrospectively from patient files. Data are expressed as mean and standard deviation or as n, median, 25th and 75th percentile values. Friedman Repeated Measures Analysis of Variance on Ranks Test, Independent Samples T Test, Mann Whitney U, Kruskal-Wallis Test were used in the analyses. p<0.05 values were considered significant. All data analyzes were performed using SPSS 22 program.
Results: Median creatinine value of CYP2C8(*1*3+**3*3) groups was significantly higher than CYP2C8(*1*1) group at 12 month(p<0,05*). The increase in creatinine value of CYP2C8 (*3*3+*1*3) groups was significantly higher than the CYP2C8*1*1 group(p<0,05*). Although the daily TAC dose was different in CYP3A5 allele groups(<0.001*) but there was no significant difference in kidney functions. There was no significant difference in drug dose, blood level and renal function between MDR1 (CC, CT ve TT) allele groups.
Conclusions: It was determined that kidney function was affected in patients with CYP2C8(*3*3+*1*3) polymorphisms in the 1-year period after transplantation, but ABCB1 polymorphisms had no effect.CYP3A5 gene polymorphism effect TAC concentration, but more patients are needed to evaluate renal function.
Supported by the Scientific Research Projects Commission(2019/2742)
Keywords: Tacrolimus, Kidney Function, CYP3A5, ABCB1, CYP2C8