A Randomized Controlled Trial Comparing the Efficacy of Cyp3a5 Genotype-Based With Body-Weight-Based Tacrolimus Dosing After Living Donor Kidney Transplantation

Patients expressing the cytochrome P450 (CYP) 3A5 gene require a higher tacrolimus dose to achieve therapeutic exposure compared with nonexpressers. This randomized-controlled study investigated whether adaptation of the tacrolimus starting dose according to CYP3A5 genotype increases the proportion of kidney transplant recipients being within thetarget tacrolimus predose concentration range (10-15ng/mL) at first steady-state. Two hundred forty living-donor, renal transplant recipients were assigned to either receive a standard, body-weight-based or a CYP3A5 genotype-based tacrolimus starting dose. At day 3, no difference in the proportion of patients having a tacrolimus exposure within the target range was observed between the standard-dose and genotype-based groups: 37.4% versus 35.6%, respectively; p=0.79. The proportion of patients with a subtherapeutic (i.e. <10ng/mL) or a supratherapeutic (i.e. >15ng/mL) Tac predose concentration in the two groups was also not significantly different. The incidence of acute rejection was comparable between both groups (p=0.82). Pharmacogenetic adaptation of the tacrolimus starting dosedoes not increase the number of patients having therapeutic tacrolimus exposure early after transplantation and does not lead to improved clinical outcome in a low immunological risk population. This randomized trial shows that in living donor kidney transplant recipients, a tacrolimus starting dose based on the CYP3A5 genotype does not increase the proportion of patients reaching the tacrolimus target concentration range at day 3 posttransplant.