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糖萼——将白蛋白尿与肾脏和心血管疾病联系起来。

The glycocalyx--linking albuminuria with renal and cardiovascular disease.

机构信息

Department of Medicine, Division of Nephrology, Einthoven Laboratory for Experimental Vascular Medicine, LUMC, Leiden University Medical Centre, Netherlands.

Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, Netherlands.

出版信息

Nat Rev Nephrol. 2015 Nov;11(11):667-76. doi: 10.1038/nrneph.2015.162. Epub 2015 Oct 13.

Abstract

Albuminuria is commonly used as a marker of kidney disease progression, but some evidence suggests that albuminuria also contributes to disease progression by inducing renal injury in specific disease conditions. Studies have confirmed that in patients with cardiovascular risk factors, such as diabetes and hypertension, endothelial damage drives progression of kidney disease and cardiovascular disease. A key mechanism that contributes to this process is the loss of the glycocalyx--a polysaccharide gel that lines the luminal endothelial surface and that normally acts as a barrier against albumin filtration. Degradation of the glycocalyx in response to endothelial activation can lead to albuminuria and subsequent renal and vascular inflammation, thus providing a pathophysiological framework for the clinical association of albuminuria with renal and cardiovascular disease progression. In this Review, we examine the likely mechanisms by which glycocalyx dysfunction contributes to kidney injury and explains the link between cardiovascular disease and albuminuria. Evidence suggests that glycocalyx dysfunction is reversible, suggesting that these mechanisms could be considered as therapeutic targets to prevent the progression of renal and cardiovascular disease. This possibility enables the use of existing drugs in new ways, provides an opportunity to develop novel therapies, and indicates that albuminuria should be reconsidered as an end point in clinical trials.

摘要

蛋白尿通常被用作肾脏疾病进展的标志物,但有证据表明,蛋白尿通过在特定疾病条件下诱导肾脏损伤,也会促进疾病进展。研究已经证实,在患有心血管危险因素(如糖尿病和高血压)的患者中,内皮损伤会导致肾脏疾病和心血管疾病的进展。导致这一过程的一个关键机制是糖萼的丧失——一种排列在腔内皮表面的多糖凝胶,它通常作为阻止白蛋白滤过的屏障。糖萼对内皮激活的反应性降解可导致蛋白尿和随后的肾脏和血管炎症,从而为蛋白尿与肾脏和心血管疾病进展的临床关联提供了病理生理学框架。在这篇综述中,我们研究了糖萼功能障碍如何导致肾脏损伤的可能机制,并解释了心血管疾病与蛋白尿之间的联系。有证据表明,糖萼功能障碍是可逆的,这表明这些机制可以被视为预防肾脏和心血管疾病进展的治疗靶点。这种可能性使我们能够以新的方式使用现有药物,为开发新的疗法提供了机会,并表明应该重新考虑蛋白尿作为临床试验的终点。

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