Contribution of bone and mineral abnormalities to cardiovascular disease in patients with chronic kidney disease.
1,25-Dihydroxyvitamin D(3) levels begin to drop early in the course of kidney disease, leading to elevated parathyroid hormone levels and disrupted mineral metabolism. Impaired mineral metabolism seems to be associated not only with bone disease but also with vascular calcification. Animal models have identified molecular mechanisms by which high mineral levels and other uremic substances induce vascular smooth muscle cells to undergo phenotypic changes that initiate the calcification process. Moreover, several epidemiologic and clinical studies showed strong associations between bone loss, arterial calcification, and cardiovascular disease in populations with and without kidney disease. This review discusses evidence that two early complications of chronic kidney disease--vitamin D deficiency and secondary hyperparathyroidism--contribute to bone and cardiovascular disease. New treatment strategies aimed at the prevention of bone loss and parathyroid hyperplasia, such as vitamin D receptor ligand therapy, calcimimetic agents, and noncalcifying phosphate binders, are being investigated for their impact on improving overall outcome in dialysis patients.
Raggi
Paolo
P
Department of Medicine and Radiology, Emory University School of Medicine, 1365 Clifton Road NE, Atlanta, GA 30322, USA. praggi@emory.edu
Kleerekoper
Michael
M
D018488:Bone Demineralization, Pathologic / Q000150:complications / Q000209:etiology; D001851:Bone Diseases, Metabolic / Q000150:complications* / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D016723:Bone Remodeling; D002114:Calcinosis / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000150:complications* / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D012307:Risk Factors; D016896:Treatment Outcome; D014808:Vitamin D Deficiency / Q000150:complications* / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology