[Prevention of extraskeletal calcifications in uremia]

Secondary hyperparathyroidism (HPTH) is a common feature in end-stage renal disease (ESRD) patients. The three main factors involved in secondary HPTH pathogenesis are high phosphate levels, hypocalcemia and vitamin D deficiency. Recently, many studies demonstrated a strong association between bone disease and cardiovascular events in chronic kidney disease patients. In addition, cardiovascular events are the most frequent cause of death in patients with chronic renal failure. Increased levels of serum phosphorus and calcium-phosphate product are directly involved in the pathogenesis of extraskeletal calcifications (blood vessels, soft tissues, etc) in dialyzed patients compared to the non-uremic population. Recent studies suggested that vascular calcification is due not only to a passive calcium-phosphate deposition on atherosclerotic arteries, but also to active mechanisms regulated by bone-associated genes. In particular, fetuin and matrix Gla-protein are two 'protective' proteins associated with reduced vascular calcification and could be the regulatory keys in preventing this process in renal failure. The limitations of calcium salts as phosphate-binders in patients with advanced renal failure have been thoroughly evaluated in the last 5 yrs. New phosphate binders, which do not contain aluminum or calcium, have been developed to reduce the risk of extraskeletal calcifications in ESRD.