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Nov 4, 2021
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Mechanistic Modeling of Kidney-Injury Molecule 1 (KIM-1) as a biomarker for Cisplatin-Induced Acute Kidney Injury

Introduction

  • Kidney Injury Molecule 1 (KIM-1) is a specific and sensitive biomarker for drug-induced acute kidney injury (AKI) prediction
  • Despite growing interest in clinical use of KIM-1 as a key biomarker for AKI diagnosis, a mechanistic model of KIM-1 that accurately predicts the kinetics of KIM-1 is still lacking.
  • Unlike normal conditions where urinary Kim-1 is not detectable, it is significantly expressed during acute kidney injury. Kim-1 was detected at high levels in proliferating bromodeoxyuridine-positive and dedifferentiated vimentin-positive epithelial cells in regenerating proximal tubules (Ichimura 1998).
  • We developed a mechanistic model of KIM-1 as part of a quantitative systems toxicology (QST) model to predict urinary KIM-1 in rats, mice and human treated with cisplatin.
  • Our objective is to characterize cisplatin-induced injury of the renal proximal tubular epithelial cells (RPTEC) and biomarker responses using Kim-1 in vivo studies

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

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