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Identification Of Early Diagnostic And Predictive Biomarkers Of Cisplatin-Induced Acute Kidney Injury Using Metabolomics, Yong Jin Lim
Identification Of Early Diagnostic And Predictive Biomarkers Of Cisplatin-Induced Acute Kidney Injury Using Metabolomics, Yong Jin Lim
Electronic Thesis and Dissertation Repository
Cisplatin is an effective chemotherapeutic agent used for the treatment of a wide variety of solid tumors and hematologic cancers. Despite its effectiveness, cisplatin is associated with several toxic effects to non-cancerous tissues. Nephrotoxicity is the main dose-limiting toxicity in cisplatin therapy, manifesting as acute kidney injury (AKI) in approximately one-third of patients receiving cisplatin. AKI is defined as an abrupt decline in kidney function and is associated with several short- and long-term adverse outcomes, including chronic kidney disease, cardiovascular disease, and mortality. AKI is currently diagnosed by increased serum creatinine (SCr) concentrations. However, SCr is a marker of functional …
N-Acetylcysteine As A Chemoprotectant Against Ifosfamide Nephrotoxicity; From Mechanism To Prevention, Lauren Hanly
N-Acetylcysteine As A Chemoprotectant Against Ifosfamide Nephrotoxicity; From Mechanism To Prevention, Lauren Hanly
Electronic Thesis and Dissertation Repository
The chemotherapy drug ifosfamide is used in the treatment of several childhood cancers. While effective, its use in children results in a 30% incidence of nephrotoxicity, and 5% incidence of Fanconi syndrome. This late effect is caused by oxidative damage, generated by chloroacetaldehyde, a toxic metabolite of ifosfamide cytochrome P450-mediated bioactivation in the kidney tubules. N-acetylcysteine has been identified as a promising strategy to mitigate nephrotoxicity through its antioxidant and glutathione stimulating properties. Furthermore, with current use in children for acetaminophen poisoning, its clinical utility is evident. Both cell and animal models have demonstrated n-acetylcysteine’s effectiveness in mitigating ifosfamide kidney …