Quantitative Systems Toxicology (QST) Modeling of Drug-Induced Acute Proximal Tubule Epithelial Cell Injury and Associated Renal Hemodynamic Responses

Authors: Hamzavi N, Gebremichael Y, Woodhead JL, Ermakov S, Howell BA
Conference: American Society of Nephrology (ASN) Kidney Week
Keywords: biomarkers, cisplatin, crystal nephropathy, drug-induced AKI, epithelial cell injury, GFR, in vitro assays, kidney function, kidney injury, KIM-1, mitochondrial dysfunction, nephrotoxic drugs, proximal tubular cells (PTCs), QST, Quantitative Systems Toxicology (QST), renal, RENAsym, RPTEC
Software: RENAsym®
Division: DILIsym Services

Introduction

  • Renal proximal tubule epithelial cells (RPTEC) are vulnerable to drug-induced toxicities which often result in acute kidney injury(AKI).
  • Drug toxic effects range from mild sub-lethal RPTEC injuries to cellular death via multiple cellular damage mechanisms. At the systems level, decline in glomerular filtration rate (GFR) is a common manifestation of AKI.
  • The complexity of pathophysiological responses (cellular, neurohormonal, hemodynamic) that lead to impaired filtration pose a challenge for reliable prediction of AKI.
  • QST modeling is a promising method for translating cellular-level renal damage to clinical manifestations of AKI.

By Nader Hamzavi, Yeshitila Gebremichael, Jeffrey L. Woodhead, Sergey Ermakov, and Brett A. Howell

Presented at American Society of Nephrology (ASN) Kidney Week, November 4-7, 2021