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尿生物标志物三叶因子 3 和白蛋白可早期检测肾管状损伤。

Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury.

机构信息

Department of Investigative Laboratory Sciences, Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania, USA.

出版信息

Nat Biotechnol. 2010 May;28(5):470-7. doi: 10.1038/nbt.1624.

Abstract

The capacities of urinary trefoil factor 3 (TFF3) and urinary albumin to detect acute renal tubular injury have never been evaluated with sufficient statistical rigor to permit their use in regulated drug development instead of the current preclinical biomarkers serum creatinine (SCr) and blood urea nitrogen (BUN). Working with rats, we found that urinary TFF3 protein levels were markedly reduced, and urinary albumin were markedly increased in response to renal tubular injury. Urinary TFF3 levels did not respond to nonrenal toxicants, and urinary albumin faithfully reflected alterations in renal function. In situ hybridization localized TFF3 expression in tubules of the outer stripe of the outer medulla. Albumin outperformed either SCr or BUN for detecting kidney tubule injury and TFF3 augmented the potential of BUN and SCr to detect kidney damage. Use of urinary TFF3 and albumin will enable more sensitive and robust diagnosis of acute renal tubular injury than traditional biomarkers.

摘要

尿三叶因子 3(TFF3)和尿白蛋白检测急性肾小管损伤的能力从未经过充分的统计学严格评估,无法替代当前临床前生物标志物血清肌酐(SCr)和血尿素氮(BUN)用于监管药物开发。我们在大鼠中发现,尿 TFF3 蛋白水平在肾小管损伤时明显降低,而尿白蛋白则明显升高。尿 TFF3 水平对非肾毒性物质无反应,而尿白蛋白忠实地反映了肾功能的变化。原位杂交将 TFF3 表达定位于外髓外层的肾小管中。白蛋白在检测肾小管损伤方面优于 SCr 或 BUN,并且 TFF3 增强了 BUN 和 SCr 检测肾脏损伤的能力。与传统生物标志物相比,使用尿 TFF3 和白蛋白将能够更敏感和更稳健地诊断急性肾小管损伤。

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