Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Pharmacology and Toxicology, MS
Committee Co-Chair (if applicable)
Cisplatin; neutral ceramidase; acute kidney injury; chronic kidney disease
Cisplatin is a commonly used chemotherapeutic agent with a dose-limiting nephrotoxicity. 30% of patients given cisplatin develop acute kidney injury (AKI). AKI increases risk of chronic kidney disease (CKD) development and mortality. Patients that don’t develop clinical AKI are still at risk for long term declines in renal function. Currently, there are no FDA approved agents to treat or prevent cisplatin-induced kidney injury (CDDP-KI). In this study, we demonstrated that neutral ceramidase (nCDase) knockout provides protection from AKI in the high-dose model of CDDP-KI. However, in the repeated low dose cisplatin (RLDC) model of injury and we found nCDase knockout does not prevent development of CKD. We also observed that nCDase knockout reduces induction of ER stress in the single high-dose model but not in the RLDC model. This study suggests there are unique mechanisms of RLDC induced kidney injury which may have hindered development of nephroprotective agents.
Sears, Sophia M., "Characterizing the roles of neutral ceramidase in cisplatin-induced kidney injury." (2019). Electronic Theses and Dissertations. Paper 3396.