State of glycocalyx barrier indicates vascular risk in dialysis patients

By Sally Robertson, B.Sc.Nov 2 2012

The glycocalyx barrier - a mesh of proteoglycans and associated glycosaminoglycans present on vascular endothelium - is impaired in patients with renal failure, probably contributing to their predisposition to endothelial dysfunction and vascular disease, say researchers.

"The state of endothelial glycocalyx and its circulating components show great promise as markers of endothelial dysfunction and their measurement may be of value in the clinical setting," comment Carmen Vlahu (Academic Medical Center, Amsterdam, the Netherlands) and colleagues.

Previous studies have shown that disruption of the glycocalyx can cause a wide range of vascular abnormalities, including increased vascular permeability, leading to generation of tissue edema, increased rolling and adhesion of leukocytes, and increased platelet adhesion.

However, the state of the endothelial glycocalyx in patients with renal failure, who are known to have endothelial dysfunction and increased risk for cardiovascular disease, is unknown, says the team.

"To our knowledge, this study is the first to examine the endothelial glycocalyx using noninvasive microvascular imaging and report increased serum levels of glycocalyx constituents and regulating enzyme in patients with ESRD [end stage renal disease]," say the researchers.

Using a novel technique called Sidestream Darkfield imaging, the team compared microvascular glycocalyx dimensions in 17 individuals on peritoneal dialysis (PD), 23 on hemodialysis (HD), and 21 age- and gender-matched healthy control individuals.

As reported in the Journal of the American Society of Nephrology, the perfused diameter (DPerf) and perfused boundary region (PBR) were significantly increased in dialysis patients compared with controls, at medians of 17.7 versus 16.4 µm and 3.6 versus 3.3 µm, respectively.

Subgroup analysis of the dialysis patients showed that the DPerf and PBR were significantly increased in both PD and HD patients compared with controls.

"The increased PBR and the corresponding increased dimension of the erytrocyte DPerf are consistent with deeper penetration of RBCs [red blood cells] into glycocalyx on the luminal surface of the endothelium," explain Vlahu and colleagues.

Consistent with increased shedding of glycocalyx from the vascular wall, the dialysis patients had higher serum levels of glycocalyx constituents hyaluronan and syndecan-1 than healthy controls, at median levels of 36 versus 17 ng/mL, and 111 versus 28 ng/mL, respectively.

"Impaired glycocalyx barrier properties, together with shedding of its constituents into the blood, are consistent with sustained pathogenic endothelial cell activation in dialysis patients and probably contribute to the aggressive vascular pathology present in this group of patients," say Vlahu and team.

"The state of endothelial glycocalyx and its circulating components could provide valuable tools to monitor vascular vulnerability, detect early stages of disease, evaluate risk, and judge the response of patients with kidney disease to treatment."

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