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      Branched-Chain Amino Acids Depletion during Hemodialysis Is Associated with Fatigue

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          Abstract

          Background: Fatigue is one of the most debilitating symptoms reported by maintenance hemodialysis (MHD) patients. Hemodialysis causes marked depletion in plasma essential amino acids. We studied the cross-sectional relationship of pre- and post-hemodialysis branched-chain amino acids (BCAAs) concentrations with fatigue in MHD patients. Methods: MHD patients self-reported fatigue during a dialysis session using the Brief Fatigue Inventory. Pre- and post-dialysis plasma levels of BCAAs (valine, leucine, and isoleucine) were measured using HPLC-mass spectrometry. Results: The mean age of study participants ( n = 114) was 54.8 ± 12.8 years. Plasma levels of BCAAs decreased significantly post-dialysis compared to pre-dialysis (303.8 ± 9.4 vs. 392.1 ± 9.4 μM/L, p < 0.0001). Fatigue score increased as a function of age ( p = 0.015). There was no association between pre-dialysis plasma levels of BCAAs and fatigue. A significant negative correlation was found between post-dialysis plasma levels of BCAAs and fatigue ( p < 0.05). Conclusions: These preliminary findings suggest that disruption in BCAAs homeostasis may play a role in precipitating fatigue.

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          Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements

          Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) are essential amino acids with protein anabolic properties, which have been studied in a number of muscle wasting disorders for more than 50 years. However, until today, there is no consensus regarding their therapeutic effectiveness. In the article is demonstrated that the crucial roles in BCAA metabolism play: (i) skeletal muscle as the initial site of BCAA catabolism accompanied with the release of alanine and glutamine to the blood; (ii) activity of branched-chain keto acid dehydrogenase (BCKD); and (iii) amination of branched-chain keto acids (BCKAs) to BCAAs. Enhanced consumption of BCAA for ammonia detoxification to glutamine in muscles is the cause of decreased BCAA levels in liver cirrhosis and urea cycle disorders. Increased BCKD activity is responsible for enhanced oxidation of BCAA in chronic renal failure, trauma, burn, sepsis, cancer, phenylbutyrate-treated subjects, and during exercise. Decreased BCKD activity is the main cause of increased BCAA levels and BCKAs in maple syrup urine disease, and plays a role in increased BCAA levels in diabetes type 2 and obesity. Increased BCAA concentrations during brief starvation and type 1 diabetes are explained by amination of BCKAs in visceral tissues and decreased uptake of BCAA by muscles. The studies indicate beneficial effects of BCAAs and BCKAs in therapy of chronic renal failure. New therapeutic strategies should be developed to enhance effectiveness and avoid adverse effects of BCAA on ammonia production in subjects with liver cirrhosis and urea cycle disorders. Further studies are needed to elucidate the effects of BCAA supplementation in burn, trauma, sepsis, cancer and exercise. Whether increased BCAA levels only markers are or also contribute to insulin resistance should be known before the decision is taken regarding their suitability in obese subjects and patients with type 2 diabetes. It is concluded that alterations in BCAA metabolism have been found common in a number of disease states and careful studies are needed to elucidate their therapeutic effectiveness in most indications.
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            Branched-chain amino acid metabolism.

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              Fatigue in patients receiving maintenance dialysis: a review of definitions, measures, and contributing factors.

              Fatigue is a debilitating symptom or side effect experienced by many patients on long-term dialysis therapy. Fatigue has a considerable effect on patient health-related quality of life and is viewed as being more important than survival by some patients. Renal providers face many challenges when attempting to reduce fatigue in dialysis patients. The lack of a reliable, valid, and sensitive fatigue scale complicates the accurate identification of this symptom. Symptoms of daytime sleepiness and depression overlap with fatigue, making it difficult to target specific therapies. Moreover, many chronic health conditions common in the long-term dialysis population may lead to the development of fatigue and contribute to the day-to-day and diurnal variation in fatigue in patients. Key to improving the assessment and treatment of fatigue is improving our understanding of potential mediators, as well as potential therapies. Cytokines have emerged as an important mediator of fatigue and have been studied extensively in patients with cancer-related fatigue. In addition, although erythropoietin-stimulating agents have been shown to mitigate fatigue, the recent controversy regarding erythropoietin-stimulating agent dosing in patients with chronic kidney disease suggests that erythropoietin-stimulating agent therapy may not serve as the sole therapy to improve fatigue in this population. In conclusion, fatigue is an important and often underrecognized symptom in the dialysis population. Possible interventions for minimizing fatigue in patients on long-term dialysis therapy should aim at improving health care provider awareness, developing improved methods of measurement, understanding the pathogenesis better, and managing known contributing factors.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2020
                July 2020
                23 June 2020
                : 51
                : 7
                : 565-571
                Affiliations
                [_a] aDepartment of Medicine, Division of Nephrology, University of Texas Health San Antonio, San Antonio, Texas, USA
                [_b] bDivision of Clinical Immunology, University of Texas Health San Antonio, San Antonio, Texas, USA
                [_c] cDepartment of Pharmacology, University of Texas Health San Antonio, San Antonio, Texas, USA
                [_d] dUniversity Health System, San Antonio, Texas, USA
                [_e] eSouth Texas Veterans Health Care System, San Antonio, Texas, USA
                Author notes
                *Subrata Debnath, Department of Medicine, Division of Nephrology, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229 (USA), nath@uthscsa.edu
                Article
                507839 Am J Nephrol 2020;51:565–571
                10.1159/000507839
                32575099
                094dd651-f895-4732-9cdb-b81e6617f7e0
                © 2020 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 26 February 2020
                : 13 April 2020
                Page count
                Tables: 2, Pages: 7
                Categories
                Novel Research Findings

                Cardiovascular Medicine,Nephrology
                Tryptophan,Outcomes,Branched-chain amino acids,Hemodialysis,Fatigue
                Cardiovascular Medicine, Nephrology
                Tryptophan, Outcomes, Branched-chain amino acids, Hemodialysis, Fatigue

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