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学科主题临床医学
Novel Assays for Detection of Urinary KIM-1 in Mouse Models of Kidney Injury
Sabbisetti, Venkata S.1; Ito, Kazumi1; Wang, Chang2; Yang, Li3; Mefferd, Stephen C.4; Bonventre, Joseph V.1
关键词Kidney Injury Molecule-1 Mouse Kim-1 Assay Ischemia Reperfusion Injury Aristolochic Acid Nephrotoxicity Biomarkers Acute Kidney Injury
刊名TOXICOLOGICAL SCIENCES
2013
DOI10.1093/toxsci/kfs268
131期:1页:13-25
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Toxicology
资助者National Institutes of Health ; National Institutes of Health
研究领域[WOS]Toxicology
关键词[WOS]MOLECULE-1 KIM-1 ; BIOMARKERS ; CREATININE
英文摘要

Editor′s Highlight: Sensitive and early noninvasive biomarkers of renal toxicity are needed to augment or replace current biomarkers. This report describes the development and validation of two bioassays for mouse urinary KIM-1 that may be of clinical value. Using a microbead-based assay and a quantitative dipstick assay, these assays demonstrated sensitivity and stability for detection of KIM-1 in models of renal toxicity when other biomarkers remained unchanged.Kidney injury molecule-1 (KIM-1) has been qualified by the Food and Drug Administration and European Medicines Agency as a urinary biomarker to monitor preclinical nephrotoxicity in rats and on a case-by-case basis for the translation of potentially nephrotoxic drugs into first-in human studies. Although mouse models are widely employed in preclinical studies, few urinary biomarker studies have been performed in mice due to limited urine availability and lack of sensitive assays. Here, we report the development and validation of two different assays for quantitative assessment of mouse urinary KIM-1 (uKIM-1) and compare the sensitivity of KIM-1 relative to other standard markers in ischemia reperfusion and aristolochic acid (AA)induced kidney injury in mice. A sensitive, reproducible, and quantitative microbead-based KIM-1 ELISA was established, which requires only 10 l urine for triplicate determination with an assay range of 12.21 pg/ml to 50ng/ml. The second assay is a laminar flow dipstick assay, which has an assay range of 195 pg/ml to 50ng/ml and provides quantitative assessment of KIM-1 in 15min. uKIM-1 levels increased with increasing time of ischemia or time after AA administration. After only 10-min ischemia followed by 24-h reperfusion, uKIM-1 was significantly elevated by 13-fold, whereas serum creatinine (sCr), blood urea nitrogen, N-acetyl--glucosaminidase (NAG), and proteinuria levels did not change. After AA administration, uKIM-1 levels were significantly upregulated by greater than threefold within 12h, whereas sCr and NAG levels were unchanged. Mouse KIM-1 was stable for multiple freeze-thaw cycles, for up to 5 days at room temperature and up to at least an year when stored at 80C.

语种英语
所属项目编号DK72381 ; DK39773
资助者National Institutes of Health ; National Institutes of Health
WOS记录号WOS:000313652900003
引用统计
被引频次:23[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53017
专题北京大学第一临床医学院_肾脏内科
作者单位1.Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Renal, Boston, MA 02115 USA
2.Cent S Univ, Xiang Ya Hosp 2, Changsha 410011, Hunan, Peoples R China
3.Peking Univ, Div Renal, Hosp 1, Beijing 100034, Peoples R China
4.BioAssay Works, Ijamsville, MD 21574 USA
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GB/T 7714
Sabbisetti, Venkata S.,Ito, Kazumi,Wang, Chang,et al. Novel Assays for Detection of Urinary KIM-1 in Mouse Models of Kidney Injury[J]. TOXICOLOGICAL SCIENCES,2013,131(1):13-25.
APA Sabbisetti, Venkata S.,Ito, Kazumi,Wang, Chang,Yang, Li,Mefferd, Stephen C.,&Bonventre, Joseph V..(2013).Novel Assays for Detection of Urinary KIM-1 in Mouse Models of Kidney Injury.TOXICOLOGICAL SCIENCES,131(1),13-25.
MLA Sabbisetti, Venkata S.,et al."Novel Assays for Detection of Urinary KIM-1 in Mouse Models of Kidney Injury".TOXICOLOGICAL SCIENCES 131.1(2013):13-25.
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