Cell- and biomarker-based assays for predicting nephrotoxicity

Huang, Johnny X., Blaskovich, Mark A. and Cooper, Matthew A. (2014) Cell- and biomarker-based assays for predicting nephrotoxicity. Expert Opinion on Drug Metabolism and Toxicology, 10 12: 1621-1635. doi:10.1517/17425255.2014.967681


Author Huang, Johnny X.
Blaskovich, Mark A.
Cooper, Matthew A.
Title Cell- and biomarker-based assays for predicting nephrotoxicity
Journal name Expert Opinion on Drug Metabolism and Toxicology   Check publisher's open access policy
ISSN 1742-5255
1744-7607
Publication date 2014-12-01
Year available 2014
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1517/17425255.2014.967681
Volume 10
Issue 12
Start page 1621
End page 1635
Total pages 15
Place of publication London, United Kingdom
Publisher Informa Healthcare
Language eng
Formatted abstract
Introduction: Drug-induced nephrotoxicity contributes to the failure rate of investigational drugs during clinical trials. We are still not able to accurately predict drug-induced nephrotoxicity during early drug discovery and development. There is an urgent need for a robust screening system that can identify nephrotoxic compounds before they reach the clinic.

Areas covered: This review discusses traditional and emerging kidney injury biomarkers that are used for the determination of nephrotoxicity and for evaluation and diagnosis of other kidney diseases. The potential for in vivo biomarkers to predict renal toxicity in high-throughput in vitro screening assays is discussed. We also compare cell types and highlight novel three-dimensional (3D) culture technologies with potential for in vitro prediction of nephrotoxicity.

Expert opinion: Traditional cell culture methods and cytotoxicity assays are well established as in vitro tests for nephrotoxicity but the correlation with in vivo results is extremely poor. Recently validated renal biomarkers show promise for early in vivo detection of nephrotoxicity, but have yet to be successfully applied for in vitro prediction of drug-induced nephrotoxicity. Advanced culture technologies ‘kidney-on-a-chip’ and 3D culture can produce biomarker signatures from relevant kidney cell types that show promise as better predictive systems.




Keyword Adverse drug reaction
Biomarker
Cell based assay
Drug discovery
Kidney
Nephrotoxicity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 15 times in Scopus Article | Citations
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