Vascular calcification and fetuin-A deficiency in chronic kidney disease

In past decades, extraosseous (including cardiovascular) calcification was predominantly regarded as a passive process of limited pathophysiological significance. It was thought that a calcium (Ca) x phosphate (P) product in excess of Ca and P solubility was the key trigger of progressive hydroxyapatite precipitation and deposition in vessels and soft tissues. Recently, however, it became apparent that calcification is a complex and highly regulated process involving inhibitors, inducers, and cell differentiation processes. It further became evident that cardiovascular manifestations of calcification predict patient outcomes in general populations, but in particular, in patients with chronic kidney disease. This review discusses the role of fetuin-A in the regulation of extraosseous and especially cardiovascular calcification processes. Fetuin-A is an inflammation-related Ca-regulatory glycoprotein and the prototype of a systemically acting calcification inhibitor. The emerging role of fetuin-A deficiency as a risk factor in dialysis patients was documented in cross-sectional studies demonstrating a significant correlation with all-cause and cardiovascular mortality.