- The leading cause of the high morbidity and mortality in hemodialysis (HD) patients is cardiovascular disease (CVD), followed by infections. A combination of patho-physiological processes is involved in the development and progression of vascular disease in HD patients including volume-overload/hypertension, atherosclerosis, calcification and thrombosis. A vicious circle of inflammation and oxidative stress, augmented by iatrogenic effects of HD lines, dialyzers and water contribute to the severity of atherosclerosis and possibly of vascular calcification. Specific metabolic risk factors include increased homocysteine levels, abnormal lipid profile and insulin resistance. The iatrogenic effect of associated therapy such as intravenous (IV) iron administration, active vitamin D derivatives, calcium containing phosphate binders, high dialysate Na concentration and possibly heparin, may add to the detrimental effects of uremia and co-morbid diseases. Potential mechanisms for iatrogenic processes may include effects of IV iron on protein oxidation and leucocyte adhesion to endothelial cells, as well as adverse effects of anticoagulation such as sub-clinical heparin induced thrombocytopenia (HIT). Preventive measures require a multidirectional approach to improve dialysis delivery and volume/blood pressure control, and to minimize adverse effects of current common essential therapies.