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Endothelial activation and circulating markers of endothelial activation in kidney disease

Nature Reviews Nephrology volume 6, pages 404–414 (2010)Cite this article

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Abstract

The recognition of a central role for the endothelium in the development of kidney disease or the development of vascular lesions in patients with established renal dysfunction has led to the emergence of methods to test different aspects of endothelium function, including in endothelium injury and repair. Endothelial-cell activation is associated with the shedding of components of the glycocalyx, adhesion molecules and endothelial microparticles into the circulation. This process may eventually result in the detachment of endothelial cells and recruitment of circulating myeloid and progenitor cells that are involved in vascular remodeling and repair. Circulating markers of endothelium activation may therefore represent novel markers of vessel wall injury. This Review describes the biology of these circulating markers of vessel wall injury, the methodologies used to measure them, and their possible relevance to patients with kidney disease.

Key Points

  • Endothelial-cell activation precedes and may stimulate the development of atherosclerotic lesions

  • The very specialized and variable phenotypes of the kidney endothelium contribute to its tendency to be a target organ in systemic disease

  • Activation of endothelial cells is accompanied by the formation and shedding of membrane microparticles and leukocyte adhesion molecules

  • Circulating CD146+ endothelial cells have been described in conditions that are associated with extensive endothelium injury

  • CD34+ progenitor cells are recruited to sites of endothelial injury and their kinetics can potentially be used as a biomarker of vascular injury

  • The clinical value of circulating markers of endothelial activation will depend on the development of standardized protocols for their measurement and insight into their quantitative relationship with clinical outcome

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Figure 1: The endothelium at a molecular level.
Figure 2: The process of endothelial-cell activation.
Figure 3: A scanning electron micrograph of CD34+ cells that were passed over tumor necrosis factor-stimulated endothelium.
Figure 4: The endothelial-cell repair processes orchestrated by circulating cells.

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Authors and Affiliations

  1. Department of Nephrology and the Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands

    Ton J. Rabelink, Hetty C. de Boer & Anton J. van Zonneveld

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  1. Ton J. Rabelink
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  2. Hetty C. de Boer
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  3. Anton J. van Zonneveld
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Correspondence to Ton J. Rabelink.

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Rabelink, T., de Boer, H. & van Zonneveld, A. Endothelial activation and circulating markers of endothelial activation in kidney disease. Nat Rev Nephrol 6, 404–414 (2010). https://doi.org/10.1038/nrneph.2010.65

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