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Evaluation of a urinary kidney biomarker panel in rat models of acute and subchronic nephrotoxicity.
- Source :
-
Toxicology [Toxicology] 2010 Nov 09; Vol. 277 (1-3), pp. 49-58. Date of Electronic Publication: 2010 Sep 09. - Publication Year :
- 2010
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Abstract
- Several novel urinary kidney biomarkers were recently approved by the US-FDA and EMA for improved detection of nephrotoxicity, but few data regarding their performance are publicly available so far. In this study, we investigated the potential of some of the newly accepted makers (Kim-1, β-2-microglobulin, cystatin C, clusterin) along with six additional urinary key proteins of kidney injury (GST-α, Timp-1, VEGF, calbindin, NGAL/lipocalin-2, osteopontin) to detect proximal tubule damage in the rat model studying either acute drug-induced kidney injury or subchronic nephrotoxicity. Candidate proteins were measured in urine samples obtained from rats treated with gentamicin (0, 60 and 120 mg/kg bw for 7 days), BI-3 [3-pyrrolidineacetic acid, 5-[[[4'-[imino[(methoxycarbonyl) amino]methyl] [1,1'-biphenyl]-4-yl]oxy]methyl]-2-oxo-, methyl ester,(3S-trans)] (0, 100, and 1000 mg/kg bw for up to 14 days) or with the mycotoxin ochratoxin A (OTA) (0, 21, 70 and 210 μg/kg bw for up to 90 days) using a Luminex(®) xMAP(®) platform. Cystatin C and NGAL appeared to be the most sensitive indicators of gentamicin nephrotoxicity, with significant changes occurring as early as day 1, and importantly before alterations in serum creatinine or blood urea nitrogen (BUN). Altered urinary excretion of KIM-1, clusterin, calbindin and Timp-1 accompanied by a rise in BUN was observed in rats with BI-3 at 1000 mg/kg bw for 14 days. In contrast, histopathological alterations induced by OTA, which preceded effects on traditional clinical parameters, were best reflected by changes in urinary Kim-1. Overall, our data confirm increased sensitivity of new markers as compared to traditional clinical chemistry parameters.<br /> (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Acute Disease
Animals
Chronic Disease
Gentamicins toxicity
Kidney Diseases pathology
Kidney Tubules, Proximal chemistry
Kidney Tubules, Proximal drug effects
Kidney Tubules, Proximal pathology
Male
Random Allocation
Rats
Rats, Inbred F344
Rats, Sprague-Dawley
Rats, Wistar
Biomarkers urine
Disease Models, Animal
Kidney Diseases chemically induced
Kidney Diseases urine
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3185
- Volume :
- 277
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 20816719
- Full Text :
- https://doi.org/10.1016/j.tox.2010.08.013