Factors Increasing Interstitial Fibrosis and Its Reduction with Personalized Dosing of Immunosuppressive Drugs after Kidney Transplantation

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Patients with CYP3A5*1 allele (CYP3A5 expressers) require a higher daily tacrolimus dose than those with CYP3A5*3/*3 genotype (non-expressers) in order to maintain target trough levels. Recently, we reported that renal cortical interstitial fibrosis (IF) from 0-hour to 1-year post-transplantation increased in non-expressers than CYP3A5 expressers. Therefore, we have started to a personalized initial dosing regimen of tacrolimus based on the CYP3A5 polymorphism. Initial oral doses of tacrolimus were 0.20mg/kg for CYP3A5 expressers and 0.10mg/kg for non-expressers. In the non-personalized regimen, all patients received 0.20mg/kg of tacrolimus.In results, the personalized medicine of tacrolimus based on the CYP3A5 polymorphism may decrease the pharmacokinetic difference between two groups, and it may contribute better graft function in non-expressers in the early post-transplantation. We are analyzing the 1-year post-transplant outcome and IF.