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

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          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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          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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            Amino acid and albumin losses during hemodialysis.

            Protein and calorie malnutrition are prevalent in chronic hemodialysis (HD) patients and has been linked to increased mortality and morbidity in this patient population. Concern has been raised that the open pore structure of high flux membranes may induce the loss of more amino acids (AA) compared to low flux membranes. To address this issue, we prospectively analyzed pre- and post-HD plasma AA profiles with three different membranes in nine patients. Simultaneously, we measured dialysate AA losses during HD. The membranes studied were: cellulosic (cuprophane-CU), low flux polymethylmethacrylate (LF-PMMA), and high flux polysulfone (HF-PS) during their first use. Our results show that pre-HD plasma AA profiles were abnormal compared to controls and decreased significantly during HD with all dialyzers. The use of HF-PS membranes resulted in significantly more AA losses into the dialysate when compared to LF-PMMA membranes (mean +/- SD; 8.0 +/- 2.8 g/dialysis for HF-PS, 6.1 +/- 1.5 g/dialysis for LF-PMMA, p < 0.05, and 7.2 +/- 2.6 g/dialysis for CU membranes, P = NS). When adjusted for surface area and blood flow, AA losses were not different between any of the dialyzers. We also measured dialysate AA losses during the sixth reuse of the HF-PS membrane. Losses of total AA increased by 50% during the sixth reuse of HF-PS membrane compared to its first use. In addition, albumin was detected in the dialysate during the sixth reuse of HF-PS membrane. We therefore measured albumin losses in all patients dialyzed with HF-PS membranes as a function of reuse.(ABSTRACT TRUNCATED AT 250 WORDS)
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              Is Open Access

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

               Milan Holecek (2018)
              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.

                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                July 2020
                23 June 2020
                : 51
                : 7
                : 565-571
                aDepartment of Medicine, Division of Nephrology, University of Texas Health San Antonio, San Antonio, Texas, USA
                bDivision of Clinical Immunology, University of Texas Health San Antonio, San Antonio, Texas, USA
                cDepartment of Pharmacology, University of Texas Health San Antonio, San Antonio, Texas, USA
                dUniversity Health System, San Antonio, Texas, USA
                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),
                507839 Am J Nephrol 2020;51:565–571
                © 2020 S. Karger AG, Basel

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                Page count
                Tables: 2, Pages: 7
                Novel Research Findings

                Cardiovascular Medicine, Nephrology

                Tryptophan, Outcomes, Branched-chain amino acids, Hemodialysis, Fatigue


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