CKD pathophysiology and complications

Abstract

Introduction and Aims: Dialysis patients have loss of glycocalyx barrier properties and increased levels of its constituents in blood. The endothelial glycocalyx is a negatively charged mesh of glycoproteins, proteoglycans and glycosaminoglycans lining the luminal side of blood vessels. It is able to reversibly bind positively charged sodium ions from circulation and might act as a sodium buffer. As a consequence, a reduction in the negatively charged components of the glycocalyx might result in an alteration in its sodium buffering capacity. Our aim was to investigate the role of the endothelial glycocalyx in sodium and fluid overload in hemodialysis patients. Methods: Investigations were performed in 23 stable hemodialysis patients. We performed Sidestream darkfield (SDF) imaging of the sublingual blood vessels using a videomicroscope. The status of endothelial glycocalyx in individual blood vessels was assessed by measuring the dynamic of the red blood cells column width near the vessel wall. In healthy conditions only the luminal part of the glycocalyx is accessible to red blood cells (RBC). When glycocalyx barrier properties are impaired, the RBC can penetrate further into the glycocalyx. Serum levels of the glycocalyx constituents hyaluronan and syndecan-1 were measured using specific ELISA's. The following parameters were recorded: the amount of ultrafiltration, the difference in weight and blood pressure before and after the dialysis session, sodium levels in blood and dialysate. Hemodynamic stability was defined as a drop in systolic blood pressure of less than 20 mmHg after a dialysis session. Results: The perfused boundary region and perfused diameter, as measured by SDF imaging, were 3.5 (3.3-3.9) m and 17.8 (17.4-18.9) m. Serum levels of hyaluronan and syndecan-1 were 36.8 (18.2-70.1) ng/ml and 111.0 (75.2-145.0) ng/ml. Serum levels of syndecan-1 positively correlated with the amount of ultrafiltration (p=0.03, r=0.43). In anuric patients, hyaluronan levels inversely correlated with the amount of ultrafiltration (p=0.01, r=-0.59), with the difference in weight before and after dialysis (p=0.01, r=-0.6), and correlated positively with the time on dialysis (p= 0.02, r=0.53). The syndecan-1 levels were positively correlated with the perfused diameter (p=0.02, r=0.52). There was no significant difference with regard to any of the study parameters between hemodinamically stable and unstable patients. Conclusions: Our results suggest a relationship between the serum levels of glycocalyx constituents and the amount of ultrafiltration. Some of the negatively charged glycosaminoglycans might maintain their ability to bind sodium even when shed from the vascular wall into circulation.