Title: Translational Assessment of Drug-Induced Proximal Tubule Injury Using a Kidney Microphysiological System.

Authors: Maass, Christian; Sorensen, Nathan B; Himmelfarb, Jonathan; Kelly, Edward J; Stokes, Cynthia L; Cirit, Murat

Published In CPT Pharmacometrics Syst Pharmacol, (2019 May)

Abstract: Drug-induced kidney injury, a major cause of acute kidney injury, results in progressive kidney disease and is linked to increased mortality in hospitalized patients. Primary injury sites of drug-induced kidney injury are proximal tubules. Clinically, kidney injury molecule-1, an established tubule-specific biomarker, is monitored to assess the presence and progression of injury. The ability to accurately predict drug-related nephrotoxicity preclinically would reduce patient burden and drug attrition rates, yet state-of-the-art in vitro and animal models fail to do so. In this study, we demonstrate the use of kidney injury molecule-1 measurement in the kidney microphysiological system as a preclinical model for drug toxicity assessment. To show clinical relevance, we use quantitative systems pharmacology computational models for in vitro-in vivo translation of the experimental results and to identify favorable dosing regimens for one of the tested drugs.

PubMed ID: 30869201

MeSH Terms: No MeSH terms associated with this publication