Evaluating the Nephrotoxicity of Exemplar Compounds Using a Mechanistic Model of Drug-Induced Acute Kidney Injury

Authors: Gebremichael Y, Woodhead JL, Hamzavi N, Tallapaka SB, Siler SQ, Howell BA
Conference: American Society of Nephrology (ASN)
Keywords: Acute kidney injury (AKI), mechanistic model, nephrotoxicity, quantitative systems toxicology (QST) model
Software: RENAsym®
Division: DILIsym Services

Background

  • Drug-induced nephrotoxicity is a common source of acute kidney injury (AKI) and a condition that complicates clinical outcomes of vulnerable patients.
  • Drugs cause nephrotoxicity by various cellular mechanisms, including mitochondrial dysfunction, oxidative stress, and others.
  • Predicting the toxicity and injury mechanisms of drugs remains a challenge.
  • We utilized a quantitative systems toxicology (QST) model to evaluate the nephrotoxicity and underlying mechanisms of two positive (cisplatin and gentamicin) and one negative (acetaminophen) control exemplar compounds

By Yeshitila Gebremichael, Jeffery L. Woodhead, Nader Hamzavi, Shailendra Tallapaka, Scott Q. Siler, and Brett A. Howell

2019 ASN Kidney Week, November 5-10, 2019, Washington, DC