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Issue 1, 2016
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Discovery of urinary metabolomic biomarkers for early detection of acute kidney injury

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Abstract

The discovery of new biomarkers for early detection of drug-induced acute kidney injury (AKI) is clinically important. In this study, sensitive metabolomic biomarkers identified in the urine of rats were used to detect cisplatin-induced AKI. Cisplatin (10 mg kg−1, i.p.) was administered to Sprague-Dawley rats, which were subsequently euthanized after 1, 3 or 5 days. In cisplatin-treated rats, mild histopathological alterations were noted at day 1, and these changes were severe at days 3 and 5. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at days 3 and 5. The levels of new urinary protein-based biomarkers, including kidney injury molecule-1 (KIM-1), glutathione S-transferase-α (GST-α), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, neutrophil, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, were significantly elevated at days 3 and 5. Among urinary metabolites, trigonelline and 3-indoxylsulfate (3-IS) levels were significantly decreased in urine collected from cisplatin-treated rats prior to histological kidney damage. However, carbon tetrachloride (CCl4), a hepatotoxicant, did not affect these urinary biomarkers. Trigonelline is closely associated with GSH depletion and results in insufficient antioxidant capacity against cisplatin-induced AKI. The predominant cisplatin-induced AKI marker appeared to be reduced in urinary 3-IS levels. Because 3-IS is predominantly excreted via active secretion in proximal tubules, a decrease is indicative of tubular damage. Further, urinary excretion of 3-IS levels was markedly reduced in patients with AKI compared to normal subjects. The area under the curve receiver operating characteristics (AUC-ROC) for 3-IS was higher than for SCr, BUN, lactate dehydrogenase (LDH), total protein, and glucose. Therefore, low urinary or high serum 3-IS levels may be more useful for early detection of AKI than conventional biomarkers.

Graphical abstract: Discovery of urinary metabolomic biomarkers for early detection of acute kidney injury

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Publication details

The article was received on 21 Jul 2015, accepted on 02 Nov 2015 and first published on 02 Nov 2015


Article type: Paper
DOI: 10.1039/C5MB00492F
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Mol. BioSyst., 2016,12, 133-144

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    Discovery of urinary metabolomic biomarkers for early detection of acute kidney injury

    A. J. Won, S. Kim, Y. G. Kim, K. Kim, W. S. Choi, S. Kacew, K. S. Kim, J. H. Jung, B. M. Lee, S. Kim and H. S. Kim, Mol. BioSyst., 2016, 12, 133
    DOI: 10.1039/C5MB00492F

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