Vascular calcification in chronic kidney disease

Abstract

Dialysis patients have increased cardiovascular morbidity, mortality, and vascular calcification, and the latter appears to impact the former. Recent evidence indicates that vascular calcification is an active, cell-mediated process. Osteoblast differentiation factor Cbfa1 and several bone-associated proteins (osteopontin, bone sialoprotein, alkaline phosphatase, type I collagen) are present in histologic sections of arteries obtained from patients with end-stage renal disease (chronic kidney disease stage V [CKD-V]). This supports the theory that vascular smooth muscle cells can dedifferentiate or transform to osteoblast-like cells, possibly by up-regulation of Cbfa1. In in vitro experiments, addition of pooled serum from dialysis patients (versus normal healthy controls) accelerated mineralization and increased expression of Cbfa1, osteopontin, and alkaline phosphatase in cultured vascular smooth muscle cells. Clinically, the pathogenesis of vascular calcification is not completely understood, although increased levels of phosphorus and/or other potential uremic toxins may play an important role by transforming vascular smooth muscle cells into osteoblast-like cells. Presumably, once this process begins, increased serum calcium X phosphorus product, or calcium load from binders, accelerates this process. In addition, it is likely that circulating inhibitors of calcification are also important. Further understanding of the pathophysiology of vascular calcification is needed to intervene appropriately.