Role of Hyperphosphatemia on Cardiovascular Disease in Dialysis Patients

The first cause of mortality in the dialysis population is cardiovascular disease. Accelerated atherosclerosis and vascular calcifications play a key role in the pathogenesis of cardiovascular disease in chronic kidney disease (CKD) patients. Mineral metabolism disorders and increased serum calcium-phosphate product have recently been investigated as factors inducing vascular calcification. Cardiovascular disease in renal failure appears to be associated with bone metabolism alterations. Hyperphosphatemia has been investigated as an inducing factor for cardiovascular morbidity in this population. Recent in vitro studies showed how vascular smooth muscle cells calcify when incubated in a medium containing elevated concentration of inorganic phosphate. Together with classical passive precipitation of calcium-phosphate in soft tissues, inorganic phosphate may cause extraskeletal calcification through "ossification" of the tunica media in the vasculature of CKD patients. In addition, the treatment of hyperphosphatemia and secondary hyperparathyroidism with calcium-based phosphate binders and calcitriol has increased the risk of vascular calcification in dialysis patients. "Second generation" therapy of hyperphosphatemia with free-calcium and aluminum phosphate binders, new vitamin D metabolites, and calcimimetics may prevent extraskeletal mineralization in uremic subjects, reducing both cardiovascular morbidity and mortality.