Mechanistic Modelling of the Linkage Between Proximal Tubule Cell Sublethal Injury and Tubular Sodium Reabsorption Impairment

Authors: Hamzavi N, Howell BA, Woodhead JL, Tallapaka SB, Siler SQ, Gebremichael Y
Conference: American Society of Nephrology (ASN)
Keywords: Acute kidney injury (AKI), mechanistic model, proximal tubular cells (PTCs), renal pathophysiology
Software: RENAsym®
Division: Quantitative Systems Pharmacology (QSP)

Introduction

  • Sublethal renal epithelial cell injury, a key manifestation of drug-induced acute kidney injury (AKI), is characterized by loss of brush border and cellular polarity of proximal tubular cells (PTCs).
  • The key cellular alterations caused by sublethal injury involve impaired energetics and associated disruptions in cytoskeletal structure and sodium transporters activity.
  • Our objective is to develop a mechanistic model relating cellular injury of AKI with renal tubular dysfunction needed to represent the complexity of renal pathophysiology.

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

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