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      Secondary hyperparathyroidism, weight loss, and longer term mortality in haemodialysis patients: results from the DOPPS

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          Abstract

          Background

          Wasting is a common complication of kidney failure that leads to weight loss and poor outcomes. Recent experimental data identified parathyroid hormone (PTH) as a driver of adipose tissue browning and wasting, but little is known about the relations among secondary hyperparathyroidism, weight loss, and risk of mortality in dialysis patients.

          Methods

          We included 42,319 chronic in‐centre haemodialysis patients from the Dialysis Outcomes and Practice Patterns Study phases 2–6 (2002–2018). Linear mixed models were used to estimate the association between baseline PTH and percent weight change over 12 months, adjusting for country, demographics, comorbidities, and labs. Accelerated failure time models were used to assess 12 month weight loss as a mediator between baseline high PTH and mortality after 12 months.

          Results

          Baseline PTH was inversely associated with 12 month weight change: 12 month weight loss >5% was observed in 21%, 18%, 18%, 17%, 15%, and 14% of patients for PTH ≥600 pg/mL, 450–600, 300–450, 150–300, 50–150, and <50 pg/mL, respectively. In adjusted analyses, 12 month weight change compared with PTH 150–299 pg/mL was −0.60%, −0.12%, −0.10%, +0.15%, and +0.35% for PTH ≥600, 450–600, 300–450, 50–150, and <50 pg/mL, respectively. This relationship was robust regardless of recent hospitalization and was more pronounced in persons with preserved appetite. During follow‐up after the 12 month weight measure [median, 1.0 (interquartile range, 0.6–1.7) years; 6125 deaths], patients with baseline PTH ≥600 pg/mL had 11% [95% confidence interval (CI), 9–13%] shorter lifespan, and 18% (95% CI, 14–23%) of this effect was mediated through weight loss ≥2.5%.

          Conclusions

          Secondary hyperparathyroidism may be a novel mechanism of wasting, corroborating experimental data, and, among chronic dialysis patients, this pathway may be a mediator between elevated PTH levels and mortality. Future research should determine whether PTH‐lowering therapy can limit weight loss and improve longer term dialysis outcomes.

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          Most cited references50

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          Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models.

          Hypotheses involving mediation are common in the behavioral sciences. Mediation exists when a predictor affects a dependent variable indirectly through at least one intervening variable, or mediator. Methods to assess mediation involving multiple simultaneous mediators have received little attention in the methodological literature despite a clear need. We provide an overview of simple and multiple mediation and explore three approaches that can be used to investigate indirect processes, as well as methods for contrasting two or more mediators within a single model. We present an illustrative example, assessing and contrasting potential mediators of the relationship between the helpfulness of socialization agents and job satisfaction. We also provide SAS and SPSS macros, as well as Mplus and LISREL syntax, to facilitate the use of these methods in applications.
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            Ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle : update 2019

            Abstract This article details an updated version of the principles of ethical authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle (JCSM) and its two daughter journals JCSM Rapid Communication and JCSM Clinical Reports. We request of all author sending to the journal a paper for consideration that at the time of submission to JCSM, the corresponding author, on behalf of all co‐authors, needs to certify adherence to these principles. The principles are as follows: all authors listed on a manuscript considered for publication have approved its submission and (if accepted) approve publication in JCSM as provided; each named author has made a material and independent contribution to the work submitted for publication; no person who has a right to be recognized as author has been omitted from the list of authors on the submitted manuscript; the submitted work is original and is neither under consideration elsewhere nor that it has been published previously in whole or in part other than in abstract form; all authors certify that the submitted work is original and does not contain excessive overlap with prior or contemporaneous publication elsewhere, and where the publication reports on cohorts, trials, or data that have been reported on before the facts need to be acknowledged and these other publications must be referenced; all original research work has been approved by the relevant bodies such as institutional review boards or ethics committees; all relevant conflicts of interest, financial or otherwise, that may affect the authors' ability to present data objectively, and relevant sources of funding of the research in question have been duly declared in the manuscript; the manuscript in its published form will be maintained on the servers of JCSM as a valid publication only as long as all statements in the guidelines on ethical publishing remain true. If any of the aforementioned statements ceases to be true, the authors have a duty to notify as soon as possible the Editors of JCSM, JCSM Rapid Communication, and JCSM Clinical Reports, respectively, so that the available information regarding the published article can be updated and/or the manuscript can be withdrawn.
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              A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease.

              The recent research findings concerning syndromes of muscle wasting, malnutrition, and inflammation in individuals with chronic kidney disease (CKD) or acute kidney injury (AKI) have led to a need for new terminology. To address this need, the International Society of Renal Nutrition and Metabolism (ISRNM) convened an expert panel to review and develop standard terminologies and definitions related to wasting, cachexia, malnutrition, and inflammation in CKD and AKI. The ISRNM expert panel recommends the term 'protein-energy wasting' for loss of body protein mass and fuel reserves. 'Kidney disease wasting' refers to the occurrence of protein-energy wasting in CKD or AKI regardless of the cause. Cachexia is a severe form of protein-energy wasting that occurs infrequently in kidney disease. Protein-energy wasting is diagnosed if three characteristics are present (low serum levels of albumin, transthyretin, or cholesterol), reduced body mass (low or reduced body or fat mass or weight loss with reduced intake of protein and energy), and reduced muscle mass (muscle wasting or sarcopenia, reduced mid-arm muscle circumference). The kidney disease wasting is divided into two main categories of CKD- and AKI-associated protein-energy wasting. Measures of chronic inflammation or other developing tests can be useful clues for the existence of protein-energy wasting but do not define protein-energy wasting. Clinical staging and potential treatment strategies for protein-energy wasting are to be developed in the future.
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                Author and article information

                Contributors
                hkomaba@tokai-u.jp
                Journal
                J Cachexia Sarcopenia Muscle
                J Cachexia Sarcopenia Muscle
                10.1007/13539.2190-6009
                JCSM
                Journal of Cachexia, Sarcopenia and Muscle
                John Wiley and Sons Inc. (Hoboken )
                2190-5991
                2190-6009
                01 June 2021
                August 2021
                : 12
                : 4 ( doiID: 10.1002/jcsm.v12.4 )
                : 855-865
                Affiliations
                [ 1 ] Division of Nephrology, Endocrinology and Metabolism Tokai University School of Medicine Isehara Japan
                [ 2 ] The Institute of Medical Sciences Tokai University Isehara Japan
                [ 3 ] Arbor Research Collaborative for Health Ann Arbor MI USA
                [ 4 ] Division of Clinical Nephrology and Rheumatology Niigata University Graduate School of Medical and Dental Sciences Niigata Japan
                [ 5 ] Medical Affairs Department Kyowa Kirin Co., Ltd. Tokyo Japan
                [ 6 ] Department of Nephrology and Renal Transplantation University Hospitals Leuven Leuven Belgium
                [ 7 ] Laboratory of Nephrology, Department of Microbiology and Immunology KU Leuven Leuven Belgium
                [ 8 ] Department of Nephrology, Skåne University Hospital Lund University Malmö Sweden
                [ 9 ] Department of Nephrology Peking University People's Hospital Beijing China
                [ 10 ] Department of Medicine Dubai Medical College Dubai United Arab Emirates
                [ 11 ] Fahad Bin Jassim Kidney Center, Department of Nephrology Hamad General Hospital, Hamad Medical Corporation Doha Qatar
                Author notes
                [*] [* ] Correspondence to: Hirotaka Komaba, Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, 143 Shimo‐Kasuya, Isehara 259‐1193, Japan. Phone: +81‐463‐93‐1121 ext 2351, Email: hkomaba@ 123456tokai-u.jp
                Author information
                https://orcid.org/0000-0002-1704-4507
                Article
                JCSM12722 JCSM-D-20-00636
                10.1002/jcsm.12722
                8350219
                34060245
                a08c50a9-a867-4019-ba63-17e9ea02a247
                © 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 April 2021
                : 27 October 2020
                : 03 May 2021
                Page count
                Figures: 7, Tables: 1, Pages: 11, Words: 4694
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                August 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.4 mode:remove_FC converted:09.08.2021

                Orthopedics
                haemodialysis,mortality,secondary hyperparathyroidism,weight loss
                Orthopedics
                haemodialysis, mortality, secondary hyperparathyroidism, weight loss

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