"Missing" inhibitors of calcification: general aspects and implications in renal failure.
In the recent past, it has become increasingly clear that extracellular calcium and phosphate homeostasis is a tightly regulated process. Since the physiological serum concentrations of calcium and phosphate are several orders of magnitude above their solubility product, mechanisms inhibiting precipitation must be operative to prevent extraosseous calcification. A number of local and systemic calcification inhibitors, including fetuin-A, matrix Gla protein, and osteoprotegerin, have been identified in recent years. Deficiency and dysregulation of such factors may contribute to morbidity and even mortality. Extraosseous calcifications occur with high prevalence in patients with end-stage renal disease. In particular, vascular manifestations are clearly associated with cardiovascular events and decreased survival. In addition to the well-established roles of hyperphosphatemia and an increased calcium x phosphate product, the biological and potential clinical roles of disturbances in calcification inhibition in uremia are discussed in this overview.
Ketteler
Markus
M
Department of Nephrology and Clinical Immunology, University Hospital Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany. mketteler@ukaachen.de
Westenfeld
Ralf
R
Schlieper
Georg
G
Brandenburg
Vincent
V
Floege
Jürgen
J
D001798:Blood Proteins / Q000502:physiology; D002114:Calcinosis / Q000209:etiology*; D002135:Calcium-Binding Proteins / Q000502:physiology; D002648:Child; D016326:Extracellular Matrix Proteins / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000150:complications; D053244:Osteoprotegerin; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D051437:Renal Insufficiency / Q000150:complications* / Q000378:metabolism; D060749:alpha-2-HS-Glycoprotein; D000097568:Matrix Gla Protein
D001798:Blood Proteins; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D053244:Osteoprotegerin; D018124:Receptors, Tumor Necrosis Factor; D060749:alpha-2-HS-Glycoprotein; D000097568:Matrix Gla Protein; C556354:AHSG protein, human; C506030:TNFRSF11B protein, human