Donor ABCB1 genetic polymorphisms influence epithelial-to-mesenchyme transition in tacrolimus-treated kidney recipients

Abstract

Aim: The contribution of epithelial–mesenchymal transition (EMT) has been suggested in renal transplant recipients receiving calcineurin inhibitors and developing nephrotoxicity. Materials & methods: We assessed whether interindividual variability in tacrolimus pharmacokinetics is associated with the occurrence in tubular cells of two EMT markers (vimentin, β-catenin) detected at 3‐month in 140 allograft biopsies. We investigated whether genetic polymorphisms affecting CYP3A5 and ABCB1 influence EMT and kidney fibrosis. Results: In univariate analysis, the donor CYP3A5*1 allele was significantly associated with a lower vimentin expression. In multivariate analysis, grafts carrying ABCB1 3435T allele(s) developed significantly less EMT and less interstitial fibrosis. Conclusion: Donor SNPs significantly influence the epithelial program in the context of kidney transplantation, and the epithelial metabolism of tacrolimus is one key to understand graft fibrogenesis.