Deficiencies of calcium-regulatory proteins in dialysis patients: a novel concept of cardiovascular calcification in uremia.
Dialysis patients suffer a manifold increase in cardiovascular mortality when compared to a nonuremic population, while this phenomenon is not sufficiently explained by an increased prevalence of traditional risk factors, such as hypercholesterolemia and hypertension. The presence of hyperphosphatemia, of an increased calcium x phosphate product, as well as the magnitude of vascular and valvular calcifications, were recently identified as specific major risk factors of cardiovascular mortality in the uremic population. Furthermore, hyperphosphatemia and an increased calcium x phosphate product could be quantitatively linked to the burden of coronary artery calcification in young dialysis patients, suggesting the correction of hyperphosphatemia as the central target for preventive therapeutic intervention. Recent studies in knockout mice, however, point to the alternative possibility that deficiencies in calcium-regulatory proteins may represent important pathomechanisms leading to extraosseous calcifications. alpha 2-Heremans Schmid glycoprotein (Ahsg/fetuin) and matrix Gla protein (MGP) are strong inhibitors of calcification in vivo. Novel evidence that deficiencies of such proteins may be involved in the pathogenesis of cardiovascular calcifications in dialysis patients will be discussed.
Ketteler
Markus
M
Department of Nephrology and Clinical Immunology, and IZKF BioMAT, University Hospital Aachen, Germany. mkettler@ukaachen.de
Wanner
Christoph
C
Metzger
Thomas
T
Bongartz
Philipp
P
Westenfeld
Ralf
R
Gladziwa
Ulrich
U
Schurgers
Leon J
LJ
Vermeer
Cees
C
Jahnen-Dechent
Willi
W
Floege
Jürgen
J
D000818:Animals; D002114:Calcinosis / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000473:pathology; D006435:Renal Dialysis; D014511:Uremia / Q000378:metabolism* / Q000473:pathology; D000097568:Matrix Gla Protein
D002118:Calcium; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein