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

Martine De Meyer, Vincent Haufroid, Laure Elens, Fabio Fusaro, Damiano Patrono, Luc De Pauw, Nada Kanaan, Eric Goffin, Michel Mourad

Research output: Contribution to journalArticle

Abstract

Background: 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. Materials and methods: 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. Results: 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, P <0.01). ABCB1 1199G>A 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. Conclusions: Donor age and ABCB1 1199G>A polymorphism affect long-term renal function after transplantation. Analysis of genetic factors offers a promising approach to calcineurin inhibitor toxicity risk assessment.

Original languageEnglish
Pages (from-to)988-995
Number of pages8
JournalJournal of Surgical Research
Volume178
Issue number2
DOIs
Publication statusPublished - Dec 2012

    Fingerprint

Keywords

  • Donor
  • Genetic polymorphisms
  • Kidney transplantation
  • Renal function

ASJC Scopus subject areas

  • Surgery

Cite this