Linked Life Data

17883283

Source:http://linkedlifedata.com/resource/pubmed/id/17883283

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2007-9-21
pubmed:abstractText
Secondary hyperparathyroidism (SHPT) is a common and serious consequence of chronic kidney disease (CKD). SHPT is a complex condition characterised by a decline in 1,25-dihydroxyvitamin D and consequent vitamin D receptor (VDR) activation, abnormalities in serum calcium and phosphorus levels, parathyroid gland hyperplasia, elevated parathyroid hormone (PTH) secretion, and systemic mineral and bone abnormalities. There are three classes of drugs used for treatment of SHPT: (i) nonselective VDR activators or agonists (VDRAs); (ii) selective VDRAs; and (iii) calcimimetics. The VDRAs act on the VDR, whereas the calcimimetics act on the calcium-sensing receptor. Calcimimetics are commonly used in conjunction with VDRA therapy. By virtue of the differences in their chemical structure, the nonselective and selective VDRAs differ in their effects on gene expression, and ultimately parathyroid gland, bone and intestine function. Medications in all three classes are effective in suppression of PTH; however, clinical studies show that calcimimetics are associated with an unfavourable tolerability profile and hypocalcaemia, whereas nonselective VDRAs, and to a lesser extent selective VDRAs, are associated with dose-limiting hypercalcaemia and hyperphosphataemia. Selective VDRAs also have minimal undesirable effects on calcium absorption in the intestine, and calcium and phosphorus mobilisation in the bone compared with nonselective VDRAs. Calcium load in patients with CKD can lead to vascular calcification, accelerated progression of cardiovascular disease and increased mortality. High serum phosphorus levels are also associated with adverse effects on cardiorenal function and survival. Recent evidence suggests that VDRAs are associated with a survival benefit in CKD patients, with a more favourable effect with selective VDRAs than nonselective VDRAs. Paricalcitol, a selective VDRA, is reported to exert specific effects on gene expression in various cell types that are involved in vascular calcification and the development of coronary artery disease. This article examines the molecular mechanisms that determine selectivity of VDRAs, and reviews the evidence for clinical efficacy, safety and survival associated with the three drug classes used for treatment of SHPT in CKD patients.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0012-6667
pubmed:author
pubmed:issnType
Print
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1981-98
pubmed:dateRevised
2008-1-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Vitamin D receptor activator selectivity in the treatment of secondary hyperparathyroidism: understanding the differences among therapies.
pubmed:affiliation
Renal Division, Ospedale San Paulo, University of Milan, Via di Rudini 8, 20142 Milan, Italy. diego.brancaccio@tiscalinet.it
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't