Genomic-derived markers for early detection of calcineurin inhibitor immunosuppressant-mediated nephrotoxicity.

ABSTRACT: Calcineurin inhibitor (CI) therapy has been associated with chronic nephrotoxicity, which limits its long-term utility for suppression of allograft rejection. In order to understand the mechanisms of the toxicity, we analyzed gene expression changes that underlie the development of CI immunosuppressant-mediated nephrotoxicity in male Sprague-Dawley rats dosed daily with cyclosporine (CsA; 2.5 or 25 mg/kg/day), FK506 (0.6 or 6 mg/kg/day), or rapamycin (1 or 10 mg/kg/day) for 1, 7, 14, or 28 days. A significant increase in blood urea nitrogen was observed in animals treated with CsA (high) or FK506 (high) for 14 and 28 days. Histopathological examination revealed tubular basophilia and mineralization in animals given CsA (high) or FK506 (low and high). We identified a group of genes whose ex

SUBMITTER: Cui Y 

PROVIDER: S-EPMC3196657 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature