The mechanism behind the increased cardiovascular risk in this population is complex but there is a strong evidence to suggest that changes in arterial stiffness play a central role. It is known that patients with CKD and ESRD have increased arterial and aortic stiffness. Examination of the aorta and conduit arteries from patients with CKD reveals features of arteriosclerosis, a disease of the arterial medial layer. Increased collagen content, collagen cross-linking, loss of elastin, and hyperplasia and hypertrophy of vascular smooth muscle cells results in arterial wall hypertrophy which together with medial calcification promotes increased stiffness. The causes of arteriosclerosis in CKD include hypertension due to sodium retention, oxidative stress, inflammation, production of advanced glycation end products, together with activation of the renin-angiotensin-aldosterone and sympathetic nervous systems. In addition, arterial stiffness exhibits a dynamic functional component. Endothelial dysfunction resulting from high levels of oxidative stress and uremic toxins, such as asymmetrical dimethyl arginine, contributes significantly to increased arterial stiffness. Increased arterial stiffness causes adverse morphological change in the left ventricle which is believed to be the basis for CHF, lethal arrhythmia, SCD and thrombo-embolic stroke.