Document Detail

Osteo-renal regulation of systemic phosphate metabolism.
MedLine Citation:
PMID:  21438115     Owner:  NLM     Status:  MEDLINE    
Impaired kidney function and subsequent skeletal responses play a critical role in disrupting phosphate balance in chronic kidney disease (CKD) patients with mineral and bone disorder (CKD-MBD). In patients with CKD-MBD, the inability of the kidney to maintain normal mineral ion balance affects bone remodeling to induce skeletal fracture and extraskeletal vascular calcification. In physiological conditions, bone-derived fibroblast growth factor 23 (FGF23) acts on the kidney to reduce serum phosphate and 1,25-dihydroxyvitamin D levels. In humans, increased bioactivity of FGF23 leads to increased urinary phosphate excretion, which induces hypophosphatemic diseases (e.g., rickets/osteomalacia). However, reduced FGF23 activity is associated with hyperphosphatemic diseases (e.g., tumoral calcinosis). In patients with CKD, high serum levels of FGF23 fail to reduce serum phosphate levels and lead to numerous complications, including vascular calcification, one of the important determinants of mortality of CKD-MBD patients. Of particular significance, molecular, biochemical and morphological changes in patients with CKD-MBD are mostly due to osteo-renal dysregulation of mineral ion metabolism. Furthermore, hyperphosphatemia can partly contribute to the development of secondary hyperparathyroidism in patients with CKD-MBD. Relatively new pharmacological agents including sevelamer hydrochloride, calcitriol analogs and cinacalcet hydrochloride are used either alone, or in combination, to minimize hyperphosphatemia and hyperparathyroidism associated complications to improve morbidity and mortality of CKD-MBD patients. This article will briefly summarize how osteo-renal miscommunication can induce phosphate toxicity, resulting in extensive tissue injuries.
Mohammed Shawkat Razzaque
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2011-03-24
Journal Detail:
Title:  IUBMB life     Volume:  63     ISSN:  1521-6551     ISO Abbreviation:  IUBMB Life     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-13     Completed Date:  2011-08-05     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  100888706     Medline TA:  IUBMB Life     Country:  England    
Other Details:
Languages:  eng     Pagination:  240-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley Periodicals, Inc.
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MeSH Terms
Bone Diseases, Metabolic / complications,  drug therapy,  metabolism
Bone and Bones / metabolism*
Fibroblast Growth Factors / metabolism
Glucuronidase / metabolism
Hyperparathyroidism / drug therapy,  etiology,  metabolism
Hyperphosphatemia / drug therapy,  etiology,  metabolism
Kidney / metabolism*
Parathyroid Hormone / metabolism
Phosphates / metabolism*
Renal Insufficiency, Chronic / complications,  drug therapy,  metabolism
Vitamin D / analogs & derivatives,  metabolism
Grant Support
Reg. No./Substance:
0/Parathyroid Hormone; 0/Phosphates; 0/fibroblast growth factor 23; 1406-16-2/Vitamin D; 62031-54-3/Fibroblast Growth Factors; 66772-14-3/1,25-dihydroxyvitamin D; EC; EC protein

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