Correlation between soluble markers of endothelial dysfunction in patients with renal failure.
OBJECTIVE
Damage to the endothelium is an important component of atherosclerosis. It has been suggested to be quantified by measuring plasma markers, such as von Willebrand factor and thrombomodulin and soluble adhesion molecules. We hypothesized there may exist a correlation between the plasma levels of von Willebrand factor and thrombomodulin as markers of endothelial cell dysfunction and the serum concentrations of soluble adhesion molecules and monocyte chemoattractant protein-1 (MCP-1) in patients with renal insufficiency, and in patients on peritoneal dialysis or hemodialysis since these three groups of kidney patients are highly prone to develop cardiovascular diseases.


RESULTS
The concentrations of von Willebrand factor and thrombomodulin in plasma were significantly higher in patients with kidney diseases as compared to healthy subjects (p = 0.017 and p < 0.001, respectively). The patients also had significantly higher concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and MCP-1 compared to healthy controls (p < 0.001 for both comparisons). There were strong correlations between the concentration of soluble intercellular adhesion molecule-1 (sICAM-1) and von Willebrand factor in patients with kidney failure (r = 0.63, p < 0.001) and between the concentration of thrombomodulin and sVCAM-1 (r = 0.61, p < 0.001). Furthermore, a negative correlation was observed between the concentration of thrombomodulin and the cell surface expression of CD11b on monocytes and granulocytes in the peripheral circulation (p < 0.01 in both cases).


CONCLUSIONS
The strong correlation between markers of endothelial dysfunction and soluble adhesion molecules in patients with renal insufficiency and on dialysis strengthen the view that an ongoing stress on endothelial cells is present in this group of patients. This may play a pathophysiological role in the development of cardiovascular disease.
Jacobson
Stefan H
SH
Department of Medicine, Division of Nephrology, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden. stefan.jacobson@ks.se
Egberg
Nils
N
Hylander
Britta
B
Lundahl
Joachim
J
D000368:Aged; D001161:Arteriosclerosis / Q000097:blood*; D004730:Endothelium, Vascular / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D018180:Thrombomodulin / Q000097:blood*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014841:von Willebrand Factor / Q000032:analysis*
D018180:Thrombomodulin; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1