Identification of noninvasive biomarkers for nephrotoxicity using HK-2 human kidney epithelial cells

Toxicological Sciences : an Official Journal of the Society of Toxicology
Sun Young KimAree Moon


The kidney is an important site of xenobiotic-induced toxicity. Because the traditional markers of renal injury indicate only severe renal damage, new biomarkers are needed for a more sensitive and reliable evaluation of renal toxicity. This study was designed to identify in vitro noninvasive biomarkers for efficient assessment of nephrotoxicity by using cisplatin as a model of nephrotoxic compounds. To this end, a comparative proteomic analysis of conditioned media from HK-2 human kidney epithelial cells treated with cisplatin was performed. Here, we identified pyruvate kinase M1/M2 isoform M2 (PKM2) and eukaryotic translation elongation factor 1 gamma (EF-1γ) as potential biomarker candidates for evaluation of nephrotoxicity. PKM2 and EF-1γ were increased by cisplatin in a kidney cell-specific manner, most likely due to cisplatin-induced apoptosis. The increase of PKM2 and EF-1γ levels in conditioned media was also observed in the presence of other nephrotoxic agents with different cytotoxic mechanisms such as CdCl2, HgCl2, and cyclosporine A. Rats treated with cisplatin, CdCl2, or HgCl2 presented increased levels of PKM2 and EF-1γ in the urine and kidney tissue. Taken together, this study identified two noninvasive biomarker...Continue Reading


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Related Concepts

Surface Enhanced Laser Desorption Ionization Mass Spectrometry
Epithelial Cell of Renal Tubule
Toxic Nephropathy
Squamous Transitional Epithelial Cell Count
Pyruvate Kinase
Mercuric chloride
Reverse Transcriptase Polymerase Chain Reaction

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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis