Roles of hyperphosphatemia in vascular calcification

Abstract

Derangemenst of mineral metabolism including hyperphosphatemia occur along with progression of chronic kidney disease (CKD) . Recent clinical studies suggest that hyperphosphatemia is a major risk factor for vascular calcification and cardiovascular mortality in dialysis patients. Two pathophysiological processes are involved in the development of vascular calcification : apoptosis and phenotypic transition to chondrocytes or osteoblasts (chondro-/osteogenic differentiation) . Inorganic phosphate has been demonstrated to induce apoptosis and calcification of vascular smooth muscle cells through inhibiting gas6/Axl/PI3K/Akt pathway (cell survival pathway) . Moreover, inorganic phosphate has been shown to promote in vitro calcification of vascular wall cells by stimulating osteoblastic differentiation through a type III sodium-dependent phosphate co-transporter (PiT-1) . These molecular mechanisms suggest that hyperphosphatemia may play a pivotal role in progression of vascular calcification in CKD.