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Issue 6, 2018
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An in vitro method for nephrotoxicity evaluation using HK-2 human kidney epithelial cells combined with biomarkers of nephrotoxicity

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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

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Publication details

The article was received on 01 Apr 2018, accepted on 06 Aug 2018 and first published on 13 Aug 2018


Article type: Paper
DOI: 10.1039/C8TX00095F
Citation: Toxicol. Res., 2018,7, 1205-1213
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    An in vitro method for nephrotoxicity evaluation using HK-2 human kidney epithelial cells combined with biomarkers of nephrotoxicity

    X. Qiu, X. Zhou, Y. Miao and B. Li, Toxicol. Res., 2018, 7, 1205
    DOI: 10.1039/C8TX00095F

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