Endothelial glycocalyx damage in kidney disease correlates with uraemic toxins and endothelial dysfunction

Hui Liew,Alun Pope,Lawrence P Mcmahon,Matthew A Roberts

doi:10.1186/s12882-020-02219-4

Hui Liew, Alun Pope + Show 2 more

Open Access

https://doi.org/10.1186/s12882-020-02219-4

Copy DOI

Journal: BMC Nephrology	Publication Date: Jan 10, 2021
Citations: 34	License type: open-access

Affiliation: Eastern Health, Monash University

Abstract

BackgroundDamage to the endothelial glycocalyx is an early indicator of vascular damage and a potential marker of endothelial dysfunction. This study aimed to assess the relationship between markers of glycocalyx damage, endothelial dysfunction, and uraemic toxins in patients with chronic kidney disease.MethodsHealthy controls, CKD patients, dialysis patients, and kidney transplant recipients had biochemical markers of glycocalyx damage (syndecan-1 and hyaluronan), endothelial dysfunction (von Willebrand factor; vWF and vascular cell adhesion molecule; VCAM-1), and uraemic toxins (indoxyl sulphate and p-cresyl sulphate) measured. In addition, Sidestream Darkfield imaging was performed using the novel GlycoCheck™ device to measure glycocalyx width by the perfused boundary region (PBR) in the sublingual microcirculation.ResultsSerum markers of glycocalyx damage were highest in the dialysis group (n = 33), followed by CKD patients (n = 32) and kidney transplant recipients (n = 30) compared to controls (n = 30): hyaluronan: 137 (16-1414), 79 (11–257), 57 (14–218) and 23 (8-116) ng/mL, respectively, p < 0.0001; syndecan-1: 81 (40–529), 46 (21–134), 39 (23–72), and 30 (12–138) ng/mL, respectively, p < 0.0001. Markers of endothelial dysfunction followed a similar pattern. No difference in the width of the PBR was detected between these groups (2.01 ± 0.35, 2.07 ± 0.27, 2.06 ± 0.28, and 2.05 ± 0.3 µm, respectively, p = 0.89). Glycocalyx damage correlated with markers of endothelial dysfunction (log-hyaluronan and log-VCAM-1: r = 0.64, p < 0.001) and levels of uraemic toxins (log-hyaluronan and log-indoxyl sulphate: r = 0.48, p < 0.001).ConclusionsLevels of biochemical markers of glycocalyx and endothelial cell damage are highest in patients receiving dialysis. Glycocalyx and endothelial damage markers correlated with each other, and with uraemic toxins. Although we could not demonstrate a change in PBR, the biochemical markers suggest that glycocalyx damage is most marked in patients with higher levels of uraemic toxins.

Highlights

Damage to the endothelial glycocalyx is an early indicator of vascular damage and a potential marker of endothelial dysfunction
Recent studies have demonstrated the existence of the endothelial glycocalyx, a protective layer overlying the endothelial lining of all blood vessels [5]
The glycocalyx is composed of core glycoprotein backbones bound to glycosaminoglycan side-chains, that interact with adsorbed plasma proteins

Summary

Introduction

Damage to the endothelial glycocalyx is an early indicator of vascular damage and a potential marker of endothelial dysfunction. Recent studies have demonstrated the existence of the endothelial glycocalyx, a protective layer overlying the endothelial lining of all blood vessels [5]. It is a potential novel biomarker of early endothelial damage [6]. The glycocalyx is composed of core glycoprotein backbones (e.g. syndecan-1) bound to glycosaminoglycan side-chains (e.g. heparan sulphate and hyaluronan), that interact with adsorbed plasma proteins Together, these constitute the endothelial surface layer, which has a varying thickness of 0.5 to 8 μm, and which protects the endothelium from damage and governs endothelial permeability to fluid and albumin [7]. Studies have demonstrated the potential for therapeutic intervention of this layer [11]

Objectives

Methods

Results

Discussion

Conclusion