ABSTRACT

Chronic kidney disease (CKD) is a common disorder that can result from a wide variety of diseases including diabetes, hypertension and glomerulonephritis, and that aff ects about 10% of the world’s population (Levey et al. 2003). For unknown reasons, CKD is an independent risk factor for the development of cardiovascular disease (Sarnak et al. 2003). Aft er stratifi cation for age, sex, race, and the presence or absence of diabetes, cardiovascular mortality in patients with advanced kidney disease is 10 to 20 times that in the general population (Sarnak et al. 2003). Th e most frequent causes of cardiovascular complications of CKD such as ischemic heart disease, sudden death, peripheral artery diseases, arterial hypertension and congestive heart failure are occlusive lesions due to atherosclerosis. Monocyte (leukocyte) adhesion to activated vascular endothelial cells and their migration into the vessel wall constitute the critical event in the initiation of atherosclerosis. Th is process is caused by the upregulation of adhesion molecules on the surface endothelial cells and an increased expression in the vascular wall of chemotactic factors to monocytes. Highly specifi c adhesive interactions between monocytes and endothelial cells are mediated by three main families of receptors: members of the immunoglobulin superfamily, selectins and integrins. Recent studies indicate that intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), members of the immunoglobulin superfamily, are among the most common participants in monocyte attraction triggered by cytokines, homocystein, lipopolysaccharides and other stimuli. Recent studies demonstrated that carbamylated low-density lipoprotein (cLDL), a product of modifi cation by urea-derived cyanate, seems to be the strongest candidate for the

missing link (Ok et al. 2005). Th e most prominent pro-atherosclerotic activity of cLDL is the activation of adhesion molecules on the surface of endothelial cells that causes the attraction of monocytes (Apostolov et al. 2007b).