Quantitative Prediction of Cisplatin-Induced Acute Kidney Injury Using RENAsym, a Mechanistic Quantitative Systems Toxicology Model, and Renal Proximal Tubule Epithelial Cell In vitro Assays

Authors: Gebremichael Y, Hamzavi N, Woodhead JL, Tallapaka SB, Siler SQ, Howell BA
Conference: American Society of Nephrology (ASN)
Keywords: Acute kidney injury (AKI), DILIsym, QST modeling, RENAsym, Toxicity
Software: RENAsym®
Division: Quantitative Systems Pharmacology (QSP)

Background

  • Nephrotoxic drugs like cisplatin cause acute kidney injury (AKI) through complex cellular mechanisms that include mitochondrial dysfunction, oxidative stress, and immune mediated injury pathways.
  • However, quantitative prediction of the underlying toxicity mechanisms remains a challenge.
  • Quantitative system toxicology (QST) modeling offers a promise for quantitative description of toxicity mechanisms leading to drug-induced AKI.
  • We developed a QST model of cisplatin induced AKI using in vitro assays to characterize key cellular injury mechanisms.

By YeshitilaGebremichael, Nader Hamzavi, Jeffrey L. Woodhead, Shailendra Tallapaka, Scott Q. Siler, and Brett A. Howell

Presented at American Society of Nephrology (ASN) Kidney Week, Oct. 20-25, 2020