Date on Master's Thesis/Doctoral Dissertation

8-2016

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Siskind, Leah

Committee Co-Chair (if applicable)

Beverly, Levi

Committee Member

Beverly, Levi

Committee Member

Arteel, Gavin

Committee Member

Lederer, Eleanor

Committee Member

Clark, Geoff

Author's Keywords

nephrotoxicity; cisplatin; fibrosis; kidney; AKI; CKD

Abstract

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.

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