VPB0021 - Correlations between oxidative stress, endothelial injury and coagulation activation in hypertensive patients with chronic kidney disease

Background: Cardiovascular disease is a major cause of death in patients with chronic kidney disease (CKD). Both conditions are rising in incidence as well as prevalence, creating poor outcomes for patients and high healthcare costs.

Aims: The aim of the present study was to establish whether enhanced oxidative stress (OS), involving endothelial injury, activation of coagulation, and inflammatory reaction, could be implicated in hypertensive patients with CKD.

Methods: 122 patients with hypertension and CKD and 63 age- and sex-matched healthy controls were included. Markers of OS, endothelial injury, coagulation, and cytokines, were measured in the plasma of hypertensive patients with CKD and of healthy controls by ELISA methods. Remodeling of the carotid arteries was assessed by measuring the intima-media thickness (IMT) as a surrogate of atherosclerotic disease in all groups.

Results: Markers of OS, endothelial injury, and extrinsic coagulation pathway activation and IMT values were significantly elevated in hypertensive patients with CKD. The von Willebrand factor antigen (vWF:Ag) levels were more increased in the hypertensive patients with CKD than in control group. Furthermore, the plasma levels of tumour necrosis factor alpha, monocyte chemo-attractant protein 1, and macrophage inflammatory protein 1 beta were significantly higher in hypertensive patients with CKD when compared with the controls. Both IMT and Cu/Zn superoxide dismutase were positively correlated with age, thrombomodulin, vWF:Ag, tissue factor, tissue factor pathway inhibitor, macrophage inflammatory protein 1 beta, and tumour necrosis factor alpha levels. Multivariate analysis identified vWF:Ag as the only independent variable significantly associated with an increased IMT.

Conclusion(s): The present study suggests that enhanced OS, involved pro-atherogenic cytokine and chemokines levels, endothelial injury, and coagulation activation may constitute cardiovascular complications in hypertensive patients with CKD. The significant, independent association between IMT and vWF:Ag should be assessed in future studies to determine whether vWF:Ag elevation is causative or a by-product of the increased IMT.