Therapeutic concentration achievement and allograft survival comparing usage of conventional tacrolimus doses and CYP3A5 CYP3A5 genotype‐guided doses in renal transplantation patients

摘要

Aims Although cytochromeP450(CYP)3A5 gene polymorphism affects personalized tacrolimus doses, there is no consensus as to whether CYP3A5 genotypes should be determined to adjust the doses. The aims were to compare the therapeutic ranges and clinical outcomes between the conventional and genotype‐guided tacrolimus doses. Methods This randomized controlled study compared 63 cases of the conventional tacrolimus dose group (0.1?mg/kg/day) with 62 cases of the genotype‐guided doses group of 0.125, 0.1 and 0.08?mg/kg for CYP3A5*1/*1 , *1/*3 , and *3/*3 genotypes for the initial 3?days of kidney transplantation. After day 3, dose adjustment occurred in both groups to achieve therapeutic concentrations. Results The genotype‐guided group had an increased proportion of patients with tacrolimus concentrations in the therapeutic range at the steady state on day 3 (40.3 vs 23.8%, P = .048). A lower proportion of over‐therapeutic concentration patients was noted in the genotype‐guided group in the CYP3A5*3/*3 genotype (9.7 vs 27%, P ?=?.013). Unexpectedly, more delayed graft functions (DGFs) were in the genotype‐guided group (41.9 vs 22.2%, P = .018) especially in the CYP3A5*1/*1 participants who might have had an aggravated DGF by a longer ischaemic time and higher serum donor creatinine levels than in the control group. There were no significant differences of glomerular filtration rates or graft or patient survivals over a median 37‐month follow‐up period. Conclusions Determination of the CYP3A5 genotype improved therapeutic range achievement. CYP3A5*1/*1 patients who have high risks of DGF should be closely monitored because of an increased risk of DGF and reduced glomerular filtration rate with high tacrolimus doses.