Arterial Calcification in Chronic Kidney Disease: Key Roles for Calcium and Phosphate

• Published in: Circulation research Vol. 109; no. 6; pp. 697 - 711
• Main Authors: Shanahan, Catherine M, Crouthamel, Matthew H, Kapustin, Alexander, Giachelli, Cecilia M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 02.09.2011; Lippincott Williams & Wilkins
• Subjects: Animals; Apoptosis; Arteries - metabolism; Arteries - pathology; Arteriosclerosis; Biological and medical sciences; Blood and lymphatic vessels; Calcification (ectopic); Calcinosis - blood; Calcinosis - pathology; Calcium - blood; Calcium - physiology; Calcium phosphate; Cardiology. Vascular system; Cardiovascular diseases; Cardiovascular Diseases - blood; Cardiovascular Diseases - pathology; Differentiation; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Extracellular matrix; Fundamental and applied biological sciences. Psychology; Homeostasis; Humans; Kidney diseases; Kidney Failure, Chronic - blood; Kidney Failure, Chronic - pathology; Kidneys; Medical sciences; Metabolism; Mortality; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Nephrology. Urinary tract diseases; Phosphate; Phosphates - blood; Phosphates - physiology; Risk factors; Smooth muscle; Urinary system involvement in other diseases. Miscellaneous; Vertebrates: cardiovascular system; Vesicles; Kidney disease; Phosphates; Urinary system disease; Calcium; vascular calcification; phosphate; Cardiovascular disease; Chronic kidney disease; Inorganic element; Vascular disease; Arterial disease; Vertebrata; Mammalia; Renal failure; Calcification; Circulatory system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.110.234914

Vascular calcification contributes to the high risk of cardiovascular mortality in chronic kidney disease (CKD) patients. Dysregulation of calcium (Ca) and phosphate (P) metabolism is common in CKD patients and drives vascular calcification. In this article, we review the physiological regulatory mechanisms for Ca and P homeostasis and the basis for their dysregulation in CKD. In addition, we highlight recent findings indicating that elevated Ca and P have direct effects on vascular smooth muscle cells (VSMCs) that promote vascular calcification, including stimulation of osteogenic/chondrogenic differentiation, vesicle release, apoptosis, loss of inhibitors, and extracellular matrix degradation. These studies suggest a major role for elevated P in promoting osteogenic/chondrogenic differentiation of VSMC, whereas elevated Ca has a predominant role in promoting VSMC apoptosis and vesicle release. Furthermore, the effects of elevated Ca and P are synergistic, providing a major stimulus for vascular calcification in CKD. Unraveling the complex regulatory pathways that mediate the effects of both Ca and P on VSMCs will ultimately provide novel targets and therapies to limit the destructive effects of vascular calcification in CKD patients.