ArticleToxicological sciences : an official journal of the Society of Toxicology2010
Performance of novel kidney biomarkers in preclinical toxicity studies.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 113 citations in OpenAlex.
- Biomarkers for early detection of sickle nephropathy.American journal of hematology · 2011Trial
- Cockayne syndrome mice reflect human kidney disease and are defective in de novo NAD biosynthesis.Cell death and differentiation · 2025Article
- Advanced Animal Replacement Testing Strategies Using Stem Cell and Organoids.International journal of stem cells · 2025Review
- Bridging organ transcriptomics for advancing multiple organ toxicity assessment with a generative AI approach.NPJ digital medicine · 2024Article
- New perspectives in application of kidney biomarkers in mycotoxin induced nephrotoxicity, with a particular focus on domestic pigs.Frontiers in microbiology · 2023Review
- Sickle cell nephropathy: A review of novel biomarkers and their potential roles in early detection of renal involvement.World journal of clinical pediatrics · 2022Review
- Mapping Adverse Outcome Pathways for Kidney Injury as a Basis for the Development of Mechanism-Based Animal-Sparing Approaches to Assessment of Nephrotoxicity.Frontiers in toxicology · 2022Article
- A Review of Specific Biomarkers of Chronic Renal Injury and Their Potential Application in Nonclinical Safety Assessment Studies.Toxicologic pathology · 2021Review
- Proteome Analysis of Urinary Biomarkers in Acute Hypercoagulable State Rat Model.Frontiers in molecular biosciences · 2021Article
- Risk assessment of ochratoxin A in food.EFSA journal. European Food Safety Authority · 2020Article
- Efficient Drug Screening and Nephrotoxicity Assessment on Co-culture Microfluidic Kidney Chip.Scientific reports · 2020Article
- Genome-Scale Model-Based Identification of Metabolite Indicators for Early Detection of Kidney Toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Sub-chronic oral toxicity assessment (90 days) of ethanolic fraction of leaves ofInterdisciplinary toxicology · 2018Article
- Diallyl disulfide attenuates acetaminophen-induced renal injury in rats.Laboratory animal research · 2016Article
- Anti-interleukin-33 Reduces Ovalbumin-Induced Nephrotoxicity and Expression of Kidney Injury Molecule-1.International neurourology journal · 2016Article
- Kupffer Cell Isolation for Nanoparticle Toxicity Testing.Journal of visualized experiments : JoVE · 2015Article
- Inhibition of Thrombin-Activated Fibrinolysis Inhibitor Increases Survival in Experimental Kidney Fibrosis.Journal of the American Society of Nephrology : JASN · 2015Article
- Evaluation of biomarkers for in vitro prediction of drug-induced nephrotoxicity: comparison of HK-2, immortalized human proximal tubule epithelial, and primary cultures of human proximal tubular cells.Pharmacology research & perspectives · 2015Article
- A method for human teratogen detection by geometrically confined cell differentiation and migration.Scientific reports · 2015Article
- Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu-Octreotate Administration in Mice.PloS one · 2015Article
Corrections and comments
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Authors and funding
18 authors at 10 institutions in 6 countries.
Funding
Abstract
The kidney is one of the main targets of drug toxicity, but early detection of renal damage is often difficult. As part of the InnoMed PredTox project, a collaborative effort aimed at assessing the value of combining omics technologies with conventional toxicology methods for improved preclinical safety assessment, we evaluated the performance of a panel of novel kidney biomarkers in preclinical toxicity studies. Rats were treated with a reference nephrotoxin or one of several proprietary compounds that were dropped from drug development in part due to renal toxicity. Animals were dosed at two dose levels for 1, 3, and 14 days. Putative kidney markers, including kidney injury molecule-1 (Kim-1), lipocalin-2 (Lcn2), clusterin, and tissue inhibitor of metalloproteinases-1, were analyzed in kidney and urine using quantitative real-time PCR, ELISA, and immunohistochemistry. Changes in gene/protein expression generally correlated well with renal histopathological alterations and were frequently detected at earlier time points or at lower doses than the traditional clinical parameters blood urea nitrogen and serum creatinine. Urinary Kim-1 and clusterin reflected changes in gene/protein expression and histopathological alterations in the target organ in the absence of functional changes. This confirms clusterin and Kim-1 as early and sensitive, noninvasive markers of renal injury. Although Lcn2 did not appear to be specific for kidney toxicity, its rapid response to inflammation and tissue damage in general may suggest its utility in routine toxicity testing.
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