Developing a more clinically-relevant mouse model of cisplatin-induced nephrotoxicity.

nephrotoxicity;cisplatin;fibrosis;kidney;AKI;CKD

Cierra N. Sharp

University:University of Louisville

Department:Pharmacology and Toxicology

关键词: nephrotoxicity;    cisplatin;    fibrosis;    kidney;    AKI;    CKD;   

Others  :  https://ir.library.louisville.edu/cgi/viewcontent.cgi?article=3525&context=etd

美国|英语

来源: The Universite of Louisville's Institutional Repository

【 摘 要 】

Cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury (AKI) in 30% of patients. Although recovery can occur after one episode of cisplatin-induced AKI, studies have indicated multiple episodes may lead to the development of chronic kidney disease (CKD), an irreversible disease with no current treatments. The standard mouse model of cisplatin-induced AKI consists of one, high dose of cisplatin (> 20 mg/kg) that is lethal to the animal three days later. This model doesn’t accurately reflect the repeated dosing regimen patients receive, and doesn’t allow for long-term outcome studies of pathologies associated with CKD. We have developed a repeated dosing model of cisplatin (7mg/kg once a week for four weeks). This model allows for the long-term survival of mice, and the associated pathology is fibrosis-the hallmark of CKD. Thus, data indicate that the repeated dosing model can be used to study AKI to CKD progression.