title: Fetuin-A and extraosseous calcification in uremia.
abstract: OBJECTIVE
  It has become increasingly clear that vascular calcification, as part of accelerated uremic atherosclerosis, may powerfully predict mortality in the dialysis population. Secondary hyperparathyroidism and its consequences explain part of this phenomenon; however, serum concentrations of calcium and phosphate ions exceed their solubility product in an aqueous solution and must be prevented from precipitation by additional mechanisms. Fetuin-A is an inflammation-related calcium-regulatory glycoprotein acting as a systemic calcification inhibitor. The emerging role of fetuin-A deficiency as a risk factor in dialysis patients was documented in a cross-sectional study demonstrating a significant correlation with all-cause and cardiovascular mortality.
  
  
  RESULTS
  In-vitro studies in vascular smooth muscle cells revealed that fetuin-A interacts directly with matrix vesicle release and may thus modulate vascular calcification processes locally and at early stages. Accordingly, prominent fetuin-A staining of calcified vessel segments obtained from uremic patients, in the absence of local expression, emphasizes its potential role as a circulating defense against overwhelming calcification. While increased fetuin-A levels positively correlated with vascular calcification in patients with diabetes and mild to moderate renal impairment, an inverse relationship was observed in dialysis patients. Both chronic inflammation and uremia may thus contribute to exhausting fetuin-A release in the late stages of kidney disease. Specific polymorphisms of the fetuin-A gene may be additional determinants of fetuin-A deficiency.
  
  
  CONCLUSIONS
  Deficiencies of calcification inhibitors such as fetuin-A are relevant pathomechanisms in the progression of uncontrolled vascular calcification and may offer potential for future therapeutic approaches.
authors.affiliation: Department of Nephrology and Clinical Immunology, University Hospital Aachen, Germany. mketteler@ukaachen.de
authors.forename: Markus
authors.initials: M
authors.lastname: Ketteler
mesh_terms: D001798:Blood Proteins / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism; D002114:Calcinosis / Q000209:etiology*; D002908:Chronic Disease; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000628:therapy; D006435:Renal Dialysis; D014511:Uremia / Q000150:complications*; D060749:alpha-2-HS-Glycoprotein
chemical_list: C556354:AHSG protein, human; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein