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Clinical Practice: Mini-Review

Free Access

Drug Discovery to Halt the Progression of Acute Kidney Injury to Chronic Kidney Disease: A Case for Phenotypic Drug Discovery in Acute Kidney Injury

Hukriede N.a, b · Vogt A.c, d · de Caestecker M.e

Author affiliations

aDepartment of Developmental Biology, bCenter for Critical Care Nephrology, cDepartment of Computational and Systems Biology, and dDrug Discovery Institute, University of Pittsburgh, Pittsburgh, PA, and eDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

Corresponding Author

Dr. Mark de Caestecker

Nephology Division

Vanderbilt University Medical Center, S3223, Medical Center North

1161 21 Street Avenue South Nashville, TN 37232 (USA)

E-Mail mark.de.caestecker@vanderbilt.edu

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Nephron 2017;137:268–272

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The cellular responses that occur following acute kidney injury (AKI) are complex and dynamic, involving multiple cells types and molecular pathways. For this reason, early selection of defined molecular targets for therapeutic intervention is unlikely to be effective in complex in vivo models of AKI, let alone Phase 3 clinical trials in patients with even more complex AKI pathobiology. Phenotypic screening using zebrafish provides an attractive alternative that does not require prior knowledge of molecular targets and may identify compounds that modify multiple targets that might be missed in more traditional target-based screens. In this review, we discuss results of an academic drug discovery campaign that used zebrafish as a primary screening tool to discover compounds with favorable absorption, metabolism, and toxicity that enhance repair when given late after injury in multiple models of AKI. We discuss how this screening campaign is being integrated into a more comprehensive, phenotypic, and target-based screen for lead compound optimization.

© 2017 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Clinical Practice: Mini-Review

Received: April 19, 2017
Accepted: April 24, 2017
Published online: June 15, 2017
Issue release date: December 2017

Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 0

ISSN: 1660-8151 (Print)
eISSN: 2235-3186 (Online)

For additional information: https://www.karger.com/NEF

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