Evaluating Nephrotoxicity of Cisplatin in Rats with RENAsym, a Mechanistic Model of Drug-Induced Acute Kidney Injury

Authors: Hamzavi N, Woodhead JL, Howell BA
Conference: SOT
Keywords: Acute kidney injury (AKI), cisplatin, mechanistic model, nephrotoxicity, PTEC, QST, QST modeling, Quantitative Systems Toxicology (QST), RENAsym
Software: RENAsym®
Division: DILIsym Services

Introduction

  • Acute kidney injury (AKI) is often initiated by cellular toxicity of proximal tubule epithelial cells (PTEC) when exposed to nephrotoxic drugs such as cisplatin.
  • Cisplatin-mediated toxicity ranges from mild PTEC injury to cellular death via several cellular damage mechanisms in association with doses of cisplatin.
  • The pathophysiology of cisplatin-induced AKI (cellular, neurohormonal, and hemodynamic) resulting in impaired filtration is a complex process which has not been completely understood.
  • RENAsym has been developed as a quantitative systems toxicology model for the prediction of drug-induced AKI by translating cellular-level in vitro mechanistic data to systems level manifestations of AKI.
  • Our aim is to predict cellular and hemodynamic responses of cisplatin-induced AKI across species and at multiple doses using RENAsym.

By: Nader Hamzavi, Jeffrey L. Woodhead, and Brett A. Howell

Presented at Society of Toxicology (SOT) 61st Annual Meeting and ToxExpo, March 27-31, 2022