Scheme for possible mechanisms of vascular calcification in CKD. Vascular calcification is a prominent feature of arterial disease in CKD and may have an impact on cardiovascular mortality through modulating both arteriosclerosis (arterial stiffening) and atherosclerosis. In CKD, abnormal mineral metabolism, predominantly hyperphosphatemia and hypercalcemia, facilitates the progression of the active process of osteogenesis in vascular smooth muscle cells (VSMCs) resulting in arteriosclerosis calcification. However, the disruption of endothelial-derived relaxing factors may signal an early stage in atherosclerosis. Hyperlipidemia, hypertension, metabolic syndrome, and CKD are the major causes of endothelial injury, partly through increase of inflammation or oxidative stress. Major cell players are endothelial cells (or valve interstitial cells; VICs), leukocytes, and intimal smooth muscle cells (SMC). Focal calcification within atherosclerotic plaques is due to both active (osteogenic) and passive (cellular necrosis) processes. The phenotypic osteocyte in calcified vessels/valves may secrete Wnt inhibitors, which may fight back inhibition of bone formation.