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      Mineral Metabolic Abnormalities and Mortality in Dialysis Patients

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          Abstract

          The survival rate of dialysis patients, as determined by risk factors such as hypertension, nutritional status, and chronic inflammation, is lower than that of the general population. In addition, disorders of bone mineral metabolism are independently related to mortality and morbidity associated with cardiovascular disease and fracture in dialysis patients. Hyperphosphatemia is an important risk factor of, not only secondary hyperparathyroidism, but also cardiovascular disease. On the other hand, the risk of death reportedly increases with an increase in adjusted serum calcium level, while calcium levels below the recommended target are not associated with a worsened outcome. Thus, the significance of target levels of serum calcium in dialysis patients is debatable. The consensus on determining optimal parathyroid function in dialysis patients, however, is yet to be established. Therefore, the contribution of phosphorus and calcium levels to prognosis is perhaps more significant. Elevated fibroblast growth factor 23 levels have also been shown to be associated with cardiovascular events and death. In this review, we examine the associations between mineral metabolic abnormalities including serum phosphorus, calcium, and parathyroid hormone and mortality in dialysis patients.

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          Most cited references104

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          Clinical epidemiology of cardiovascular disease in chronic renal disease.

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            Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid.

            Maintenance of a stable internal environment within complex organisms requires specialized cells that sense changes in the extracellular concentration of specific ions (such as Ca2+). Although the molecular nature of such ion sensors is unknown, parathyroid cells possess a cell surface Ca(2+)-sensing mechanism that also recognizes trivalent and polyvalent cations (such as neomycin) and couples by changes in phosphoinositide turnover and cytosolic Ca2+ to regulation of parathyroid hormone secretion. The latter restores normocalcaemia by acting on kidney and bone. We now report the cloning of complementary DNA encoding an extracellular Ca(2+)-sensing receptor from bovine parathyroid with pharmacological and functional properties nearly identical to those of the native receptor. The novel approximately 120K receptor shares limited similarity with the metabotropic glutamate receptors and features a large extracellular domain, containing clusters of acidic amino-acid residues possibly involved in calcium binding, coupled to a seven-membrane-spanning domain like those in the G-protein-coupled receptor superfamily.
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              Phosphate regulation of vascular smooth muscle cell calcification.

              Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic and uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extracellular inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralization in vitro was examined. HSMCs cultured in media containing normal physiological levels of inorganic phosphate (1.4 mmol/L) did not mineralize. In contrast, HSMCs cultured in media containing phosphate levels comparable to those seen in hyperphosphatemic individuals (>1.4 mmol/L) showed dose-dependent increases in mineral deposition. Mechanistic studies revealed that elevated phosphate treatment of HSMCs also enhanced the expression of the osteoblastic differentiation markers osteocalcin and Cbfa-1. The effects of elevated phosphate on HSMCs were mediated by a sodium-dependent phosphate cotransporter (NPC), as indicated by the ability of the specific NPC inhibitor phosphonoformic acid, to dose dependently inhibit phosphate-induced calcium deposition as well as osteocalcin and Cbfa-1 gene expression. With the use of polymerase chain reaction and Northern blot analyses, the NPC in HSMCs was identified as Pit-1 (Glvr-1), a member of the novel type III NPCs. These data suggest that elevated phosphate may directly stimulate HSMCs to undergo phenotypic changes that predispose to calcification and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. The full text of this article is available at http://www.circresaha.org.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                22 March 2013
                March 2013
                : 5
                : 3
                : 1002-1023
                Affiliations
                [1 ]Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1, Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan; E-Mail: kokada@ 123456med.nihon-u.ac.jp
                [2 ]Division of General Medicine, Department of Internal Medicine, Nihon University School of Medicine, 30-1, Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan; E-Mail: souma.masayoshi@ 123456nihon-u.ac.jp
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: abe.masanori@ 123456nihon-u.ac.jp ; Tel.: +81-3-3972-8111; Fax: +81-3-3972-8311.
                Article
                nutrients-05-01002
                10.3390/nu5031002
                3705332
                23525083
                dea7e651-b709-4d95-9946-73166a9cc04e
                © 2013 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 10 January 2013
                : 19 February 2013
                : 07 March 2013
                Categories
                Review

                Nutrition & Dietetics
                calcium,chronic kidney disease,phosphate,mineral and bone disorder,vascular calcification

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