Kidney Injury Molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury
Kidney Injury Molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury
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DOI：
10.1046/j.1523-1755.2002.00433.x
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发表时间：
2002-07-01
影响因子：
19.6
通讯作者：
Bonventre, JV
中科院分区：
文献类型：
--
作者：
Han, WK;Bailly, V;Bonventre, JV
背景传统的血液和尿液指标用于诊断各种肾脏疾病是不敏感和非特异性的。肾损伤分子-1（KIM-1）是一种1型跨膜蛋白，具有免疫球蛋白和粘蛋白结构域，其在缺血后大鼠肾脏近端小管中的表达显著上调。KIM-1的胞外域从细胞脱落。本研究旨在探讨KIM-1是否存在于人类急性肾功能衰竭中，并可能作为急性肾小管损伤的尿液标志物。通过免疫组织化学方法对6例经活检证实的急性肾小管坏死（ATN）患者的肾组织样本进行KIM-1表达评估。尿液样本收集了额外的32例各种急性和慢性肾脏疾病，以及从8个正常对照。采用免疫法检测尿KIM-1蛋白，ELISA法定量。在6例确诊为ATN的患者中，6例活检组织中近端小管细胞广泛表达KIM-1。与其他形式的急性肾功能衰竭（0.63 +/- 0.17，P <0.01; N = 16）或慢性肾病（0.72 +/- 0.37，P <0.01：N = 9）患者相比，缺血性ATN患者的标准化尿KIM-1水平（2.92 +/-0.61 N = 7）显著更高。校正年龄、性别、初始损伤和尿液采样之间的时间延迟长度，标准化KIM-1增加一个单位与ATN存在的风险大于12倍（OR 12.4，95%CI 1.2至119）相关。其他尿液生物标志物的浓度，包括总蛋白。γ-谷氨酰转移酶和碱性磷酸酶与临床诊断组无关。可溶形式的人KIM-1可以在ATN患者的尿液中检测到，并且可以作为肾近端小管损伤的有用生物标志物，促进疾病的早期诊断并作为诊断试剂。
Background. Traditional blood and urine markers for the diagnosis of various renal diseases are insensitive and nonspecific. Kidney Injury Molecule-1 (KIM-1) is a type 1 transmembrane protein, with an immunoglobulin and mucin domain, whose expression is markedly up-regulated in the proximal tubule in the post-ischemic rat kidney. The ectodomain of KIM-1 is shed from cells. The current studies were carried out to evaluate whether KIM-1 is present in human acute renal failure and might serve as a urinary marker of acute renal tubular injury.Methods. Kidney tissue samples from six patients with biopsy-proven acute tubular necrosis (ATN) were evaluated by immunohistochemistry for expression of KIM-1. Urine samples were collected from an additional thirty-two patients with various acute and chronic renal diseases, as well as from eight normal controls. Urinary KIM-1 protein was detected by immunoassay and was quantified by ELISA.Results. There was extensive expression of KIM-1 in proximal tubule cells in biopsies from 6 of 6 patients with confirmed ATN. The normalized urinary KIM-1 levels were significantly higher in patients with ischemic ATN (2.92 +/- 0.61 N = 7) compared to levels in patients with other forms of acute renal failure (0.63 +/- 0.17, P < 0.01; N = 16) or chronic renal disease (0.72 +/- 0.37, P < 0.01: N = 9). Adjusted for age, gender, length of time delay between the initial insult and sampling of the urine, a one-unit increase in normalized KIM-1 was associated with a greater than 12-fold (OR 12.4, 95% CI 1.2 to 119) risk for the presence of ATN. Concentrations of other urinary biomarkers, including total protein. gamma-glutamyltransferase, and alkaline phosphatase, did not correlate with clinical diagnostic groupings.Conclusions. A soluble form of human KIM-1 can be detected in the urine of patients with ATN and may serve as a useful biomarker for renal proximal tubule injury facilitating the early diagnosis of the disease and serving as a diagnostic discriminator.