A SINGLE-CENTER PHARMACOGENETIC STUDY OF DONOR AND RECIPIENT TO IMPROVE THE EFFICACY AND REDUCE THE NEPHROTOXICITY OF TACROLIMUS AFTER KIDNEY TRANSPLANTATION.

The aims of the current study are two-fold. First we will investigate whether a CYP3A5 genotype-based tacrolimus dosing strategy will result in improved clinical outcomes as compared with a standard tacrolimus dosing regimen based on bodyweight. Second, we will investigate if ABCB1 and CYP3A5 and single-nucleotide polymorphisms (SNPs) in their encoding genes are associated with the development of tacrolimus-induced nephrotoxicity after kidney transplantation.

N/A

Time frame: three months.

Patients in the standard tacrolimus dose group will receive a dose of 0.20 mg tacrolimus/kg bodyweight per day in two equally divided doses. Patients in the CYP3A5 dosing group will receive a tacrolimus dose of 0.30 mg/kg per day in two equally divided doses if they express CYP3A5 (carriers of the CYP3A5*1 allele) or will receive a tacrolimus dose of 0.15 mg/kg bodyweight in two equally divided doses if they are CYP3A5 non-expressers (CYP3A5*3 allele homozygotes). The tacrolimus dose will be adjusted according to pre-dose concentrations (C0) aiming for target concentrations of 10-15 ng/mL in weeks 1-2, 8-12 ng/mL in weeks 3 and 4 and 5-10 ng/mL thereafter.



All patients will undergo protocol biopsies at t = 0 (pre-implantation biopsy) and at 3 months after transplantation. The pre-implantation biopsy is routinely performed in all patients. The biopsy at 3 months is taken as part of the study protocol.