Kidney injury molecule-1 is an early biomarker of cadmium nephrotoxicity
Kidney injury molecule-1 is an early biomarker of cadmium nephrotoxicity
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DOI：
10.1038/sj.ki.5002467
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发表时间：
2007-10-01
影响因子：
19.6
通讯作者：
Bonventre, J. V.
中科院分区：
文献类型：
--
作者：
Prozialeck, W. C.;Vaidya, V. S.;Bonventre, J. V.
镉（Cd）暴露导致以多尿和蛋白尿为特征的近端小管损伤。肾损伤分子-1（Kim-1）是一种跨膜糖蛋白，通常在成熟肾脏中检测不到，但在肾毒性损伤后上调并脱落到尿液中。在这项研究中，我们确定金-1可能是一个有用的早期生物标志物镉肾毒性。雄性Sprague-Dawley大鼠每天注射镉，持续12周。每周尿样分析Kim-1、蛋白质、肌酐、金属硫蛋白和克拉拉细胞蛋白CC-16。6周时在尿液中检测到显著水平的Kim-1，并且在整个治疗期间持续增加。Kim-1的出现发生在蛋白尿发作前4-5周，金属硫蛋白和CC-16出现前1-3周。高剂量的镉引起更高的Kim-1排泄。逆转录-聚合酶链反应（RT-PCR）表达分析表明，Kim-1转录水平增加6周后，在低剂量的镉。免疫组织化学分析显示，Kim-1存在于近端小管细胞的镉治疗的大鼠。我们的研究结果表明，Kim-1可能是一个有用的生物标志物的早期阶段，镉诱导的近端小管损伤。
Cadmium ( Cd) exposure results in injury to the proximal tubule characterized by polyuria and proteinuria. Kidney injury molecule-1 ( Kim-1) is a transmembrane glycoprotein not normally detected in the mature kidney, but is upregulated and shed into the urine following nephrotoxic injury. In this study, we determine if Kim-1 might be a useful early biomarker of Cd nephrotoxicity. Male Sprague-Dawley rats were given daily injections of Cd for up to 12 weeks. Weekly urine samples were analyzed for Kim-1, protein, creatinine, metallothionein, and Clara cell protein CC-16. Significant levels of Kim-1 were detected in the urine by 6 weeks and continued to increase throughout the treatment period. This appearance of Kim-1 occurred 4-5 weeks before the onset of proteinuria, and 1-3 weeks before the appearance of metallothionein and CC-16. Higher doses of Cd gave rise to higher Kim-1 excretion. Reverse transcriptase-polymerase chain reaction ( RT-PCR) expression analysis showed that Kim-1 transcript levels were increased after 6 weeks at the low dose of Cd. Immunohistochemical analysis showed that Kim-1 was present in proximal tubule cells of the Cd-treated rats. Our results suggest that Kim-1 may be a useful biomarker of early stages of Cd-induced proximal tubule injury.