Donor age and ABCB1 1199G>A genetic polymorphism are independent factors affecting long-term renal function after kidney transplantation

In renal tubular cells, cytochrome P4503A enzyme and adenosine triphosphate-binding cassette transporter activities result in intracellular drug or metabolite exposure variability, depending on genetic polymorphisms. Our aim was to establish whether long-term renal function is affected by genetic polymorphisms in biotransformation enzymes and drug transporters of the donor after kidney transplantation.The study was conducted in a selected cohort of 97 kidney recipients. Genotyping of donors was performed on renal biopsy samples obtained before transplantation. Serum creatinine levels and Cockcroft-Gault estimated glomerular filtration rate were considered 1 y after transplantation and at the last follow-up.Long-term function was significantly better in recipients of an organ from donors carrying the ABCB1 1199A mutated allele (median and range creatinine values were 1.1 mg/dL [0.8-1.5mg/dL] in case of at least one ABCB1 1199A allele versus 1.5 mg/dL [0.7-3.7 mg/dL] for homozygous carriers of wild-type allele, P0.01). ABCB1 1199GA polymorphism and donor age had an independent impact on both serum creatinine and estimated glomerular filtration rate. Unlike donor age, the mutated ABCB1 1199A allele was found to have a protective effect on renal function.Donor age and ABCB1 1199GA polymorphism affect long-term renal function after transplantation. Analysis of genetic factors offers a promising approach to calcineurin inhibitor toxicity risk assessment.