|
Title
|
|
|
|
Calcium-sensing receptor, calcimimetics, and cardiovascular calcifications in chronic kidney disease
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| Renal function impairment goes along with a disturbed calcium, phosphate, and vitamin D metabolism, resulting in secondary hyperparathyroidism (sHPT). These mineral metabolism disturbances are associated with soft tissue calcifications, particularly arteries, cardiac valves, and myocardium, ultimately associated with increased risk of mortality in patients with chronic kidney disease (CKD). sHPT may lead to cardiovascular calcifications by other mechanisms including an impaired effect of parathyroid hormone (PTH), and a decreased calcium-sensing receptor (CaR) expression on cardiovascular structures. PTH may play a direct role on vascular calcifications through activation of a receptor, the type-1 PTH/PTHrP receptor, normally attributed to PTH-related peptide (PTHrP). The CaR in vascular cells may also play a role on vascular mineralization as suggested by its extremely reduced expression in atherosclerotic calcified human arteries. Calcimimetic compounds increasing the CaR sensitivity to extracellular calcium efficiently reduce serum PTH, calcium, and phosphate in dialysis patients with sHPT. They upregulate the CaR in vascular cells and attenuate vascular mineralization in uremic states. In this article, the pathophysiological mechanisms associated with cardiovascular calcifications in case of sHPT, the impact of medical and surgical correction of sHPT, the biology of the CaR in vascular structures and its function in CKD state, and finally the role played by the CaR and its modulation by the calcimimetics on uremic-related cardiovascular calcifications are reviewed. Kidney International (2012) 82, 19-25; doi:10.1038/ki.2012.69; published online 21 March 2012 |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Kidney international / International Society of Nephrology. - New York, N.Y., 1972, currens
| |
|
Publication
|
|
|
|
New York, N.Y.
:
2012
| |
|
ISSN
|
|
|
|
0085-2538
[print]
1523-1755
[online]
| |
|
DOI
|
|
|
|
10.1038/KI.2012.69
| |
|
Volume/pages
|
|
|
|
82
:1
(2012)
, p. 19-25
| |
|
ISI
|
|
|
|
000305351300004
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (publisher's version - intranet only)
|
|
|
|
| |
|