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The glycocalyx—linking albuminuria with renal and cardiovascular disease

Nature Reviews Nephrology volume 11, pages 667–676 (2015)Cite this article

Subjects

Key Points

  • The luminal surface of the glomerular endothelium is covered with a hydrogel called the glycocalyx, which is comprised of glycosoaminoglycans, glycoproteins and associated serum proteins

  • The glycocalyx acts as a barrier against protein filtration across the endothelium

  • Loss of glycocalyx function might underlie the association of albuminuria with progression of renal and cardiovascular disease

  • Albuminuria as a consequence of glycocalyx dysfunction is likely to be a causal factor in the progression of renal disease

  • Understanding the mechanisms of disease that result from glycocalyx dysfunction could help to develop clinical trials in which albuminuria is an end point

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.

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Figure 1: The structure of the glycocalyx.
Figure 2: Mechanism of glycocalyx degradation.
Figure 3: Loss of the glycocalyx leads to podocyte and kidney injury.
Figure 4: Development of atherosclerotic lesions after loss of the glycocalyx.

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Acknowledgements

T.J.R. was supported by the Glycoren consortium grant of the Dutch Kidney Foundation (CP09.03).

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

    Ton J. Rabelink

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

    Dick de Zeeuw

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T.J.R. researched data for the article. Both authors made substantial contributions to discussion of content, wrote the article, and reviewed and/or edited the manuscript before submission.

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Rabelink, T., de Zeeuw, D. The glycocalyx—linking albuminuria with renal and cardiovascular disease. Nat Rev Nephrol 11, 667–676 (2015). https://doi.org/10.1038/nrneph.2015.162

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