Issue 6, 2018

An in vitro method for nephrotoxicity evaluation using HK-2 human kidney epithelial cells combined with biomarkers of nephrotoxicity

Abstract

The kidney is one of the major target organs for drug-induced toxicity. During drug development, the traditional markers of nephrotoxicity indicate only severe and late damage, which leads to high costs. The new biomarkers are needed for a more sensitive and reliable evaluation of nephrotoxicity, especially for the regulatory accepted and validated in vitro model. We developed an in vitro model based on the HK-2 cell using the biomarkers of nephrotoxicity as endpoints for the evaluation of nephrotoxicity. The predictive performance of the biomarkers including LDH, GGT, KIM-1, clusterin, CysC, NGAL, TIMP-1, GSTπ and osteopontin was evaluated with 22 well characterized compounds. The area under the curve (AUC) values of KIM-1, clusterin, CysC and osteopontin ranged between 0.79 and 0.84. The combination of clusterin, KIM-1 and/or osteopontin improved the AUC value (ranging between 0.88 and 0.95) compared to one biomarker. Taken together, these results suggest that the model based on the HK-2 cell using clusterin, osteopontin, CysC and KIM-1 as endpoints would allow the prediction of nephrotoxicity at early preclinical stages.

Graphical abstract: An in vitro method for nephrotoxicity evaluation using HK-2 human kidney epithelial cells combined with biomarkers of nephrotoxicity

Supplementary files

Article information

Article type
Paper
Submitted
01 Apr 2018
Accepted
06 Aug 2018
First published
13 Aug 2018

Toxicol. Res., 2018,7, 1205-1213

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