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      Parathyroid Hormone Fragments: New Targets for the Diagnosis and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder

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          Abstract

          As a common disorder, chronic kidney disease (CKD) poses a great threat to human health. Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a complication of CKD characterized by disturbances in the levels of calcium, phosphorus, parathyroid hormone (PTH), and vitamin D; abnormal bone formation affecting the mineralization and linear growth of bone; and vascular and soft tissue calcification. PTH reflects the function of the parathyroid gland and also takes part in the metabolism of minerals. The accurate measurement of PTH plays a vital role in the clinical diagnosis, treatment, and prognosis of patients with secondary hyperparathyroidism (SHPT). Previous studies have shown that there are different fragments of PTH in the body's circulation, causing antagonistic effects on bone and the kidney. Here we review the metabolism of PTH fragments; the progress being made in PTH measurement assays; the effects of PTH fragments on bone, kidney, and the cardiovascular system in CKD; and the predictive value of PTH measurement in assessing the effectiveness of parathyroidectomy (PTX). We hope that this review will help to clarify the value of accurate PTH measurements in CKD-MBD and promote the further development of multidisciplinary diagnosis and treatment.

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          Parathyroid hormone: anabolic and catabolic actions on the skeleton.

          Parathyroid hormone (PTH) is essential for the maintenance of calcium homeostasis through, in part, its actions to regulate bone remodeling. While PTH stimulates both bone formation and bone resorption, the duration and periodicity of exposure to PTH governs the net effect on bone mass, that is whether it is catabolic or anabolic. PTH receptor signaling in osteoblasts and osteocytes can increase the RANKL/OPG ratio, increasing both osteoclast recruitment and osteoclast activity, and thereby stimulating bone resorption. In contrast, PTH-induced bone formation is explained, at least in part, by its ability to downregulate SOST/sclerostin expression in osteocytes, permitting the anabolic Wnt signaling pathway to proceed. The two modes of administration of PTH, that is, continuous vs. intermittent, can regulate, in bone cells, different sets of genes; alternatively, the same sets of genes exposed to PTH in sustained vs. transient way, will favor bone resorption or bone formation, respectively. This article reviews the effects of PTH on bone cells that lead to these dual catabolic and anabolic actions on the skeleton.
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            Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis.

            The management of chronic kidney disease-mineral and bone disorder requires the assessment of bone turnover, which most often is based on parathyroid hormone (PTH) concentration, the utility of which remains controversial.
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              Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease.

              Patients with chronic kidney disease and end-stage renal disease are at 5- to 10-fold higher risk for developing cardiovascular disease (CVD) than age-matched controls. Clinically, CVD in this population manifests as coronary artery disease, arrhythmias, stroke, or congestive heart failure. Beyond the traditional risk factors (eg, diabetes mellitus and hypertension), uremia-specific factors that arise from accumulating toxins also contribute to the pathogenesis of CVD. In this review, we summarize the literature on the epidemiology of both traditional and uremia-related CVD and focus on postulated mechanisms of the latter. In the context of current and emerging diagnostics and therapies for CVD, we highlight what we interpret as major gaps in the medical management of this growing population that need to be addressed with targeted epidemiological and translational research. Finally, we describe the global challenges associated with the recognition and management of uremia-related CVD in developed and developing nations.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2018
                29 November 2018
                : 2018
                : 9619253
                Affiliations
                1Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu Province 210029, China
                2Nanjing Medical University, Nanjing, Jiangsu Province 211166, China
                Author notes

                Academic Editor: Detlef H. Krieter

                Author information
                http://orcid.org/0000-0002-1363-3101
                Article
                10.1155/2018/9619253
                6304519
                30627584
                22cdb630-a655-42e1-a084-9471ce578a44
                Copyright © 2018 Huimin Chen et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 July 2018
                : 22 October 2018
                : 28 October 2018
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81270408
                Award ID: 81570666
                Funded by: International Society of Nephrology (ISN) Clinical Research Program
                Award ID: 18-01-0247
                Funded by: Construction Program of Jiangsu Provincial Clinical Research Center Support System
                Award ID: BL2014084
                Funded by: Jiangsu Province Key Medical Personnel Project
                Award ID: RC201162
                Award ID: ZDRCA2016002
                Funded by: Six Major Talents Summit of Jiangsu Province
                Award ID: 2010 (IB10)
                Funded by: Chinese Society of Nephrology
                Award ID: 13030300415
                Categories
                Review Article

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