SEMINAR: Understanding Mechanisms of Cisplatin-induced Nephrotoxicity: The Model Matters

Leah J. Siskind, Ph.D.
When Sep 11, 2018
from 12:00 PM to 01:30 PM
Where Shumaker Research Bldg, RM 139
Contact Name
Contact Phone 502-852-7485
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Abstract:Acute kidney injury (AKI) is the most critical dose-limiting toxicity in cancer patients treated with a variety of cancer chemotherapeutics, including cisplatin. Cisplatin, one of the most common and effective chemotherapeutics for treating many cancer types, induces AKI in thirty percent of patients, requiring an altered dosing regimen that is not ideal for reducing tumor burden. It is now understood that exposure to nephrotoxic agents significantly increases a patient’s long-term risk of developing CKD (chronic kidney disease). Data indicate that kidney function is decreased five or more years after completing cisplatin treatment regardless of whether the patient suffered a bona fide AKI event during the course of treatment. With improved diagnosis and treatment of cancers, there is increased longterm patient survival; hence, there is an increased number of cancer survivors expected to develop CKD and end-stage renal disease as a result of the long-term side effects of cisplatin. Despite decades of research, there are no treatments for prevention or treatment of AKI or AKI-to-CKD transition, other than supportive care. To better understand cisplatin-induced AKI and its progression to CKD, we developed a new model of cisplatin-induced AKI that more accurately reflects the dosing and timing of treatments in the clinic, takes into account the comorbidities of cancer patients, and allows for detailed analysis of the AKI-to-CKD transition. Using this new model, we have identified a novel therapeutic target for the prevention and treatment of cisplatin-induced AKI and CKD.

Speaker: Dr.Siskind completed her PhD in 2003 from the University and completed post-doctoral training at the Medical University of South Carolina in 2009.  Dr. Siskind began her first faculty position at the Medical University of South Carolina in 2009 and 2012 she received her first R01 to study the role of sphingolipids in acute kidney injury. In 2013, Dr. Siskind was recruited to the Department of Pharmacology and Toxicology at the University of Louisville as an Associate Professor.  In 2018, Dr. Siskind was awarded tenure and was promoted to Associate Vice-Chair for Graduate Education and the Director of Graduate Studies.

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