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      Slipping Through the Pores: Hypoalbuminemia and Albumin Loss During Hemodialysis

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          Abstract

          Hypoalbuminemia results when compensatory mechanisms are unable to keep pace with derangements in catabolism/loss and/or decreased synthesis of albumin. Across many disease states, including chronic kidney disease (CKD), hypoalbuminemia is a well-established, independent risk factor for adverse outcomes, including mortality. In the setting of CKD, reduced serum albumin concentrations are often a manifestation of protein-energy wasting, a state of metabolic and nutritional alterations resulting in reduced protein and energy stores. The progression of CKD to kidney failure and the initiation of maintenance hemodialysis (HD) further predisposes an already at-risk population toward hypoalbuminemia such that approximately 60% of HD patients have albumin concentrations <4.0 g/dl. Albumin loss into the dialysate through the dialyzer appears to be a potentially modifiable cause of hypoalbuminemia in some patients. A group of newer dialyzers for maintenance HD—sometimes termed protein-leaking or medium cut-off membranes—aim to improve clearance of middle molecules (vs high flux dialyzers) but are associated with increased albumin losses. In this article, we will examine the impact of dialyzer selection on albumin losses during conventional HD, including the clinical relevance of such losses on serum albumin levels. Data on the clinical relevance of albumin losses during dialysis and current gaps in the evidence base are also discussed.

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          Most cited references73

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          US Renal Data System 2018 Annual Data Report: Epidemiology of Kidney Disease in the United States

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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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              Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences.

              Protein-energy malnutrition (PEM) and inflammation are common and usually concurrent in maintenance dialysis patients. Many factors that appear to lead to these 2 conditions overlap, as do assessment tools and such criteria for detecting them as hypoalbuminemia. Both these conditions are related to poor dialysis outcome. Low appetite and a hypercatabolic state are among common features. PEM in dialysis patients has been suggested to be secondary to inflammation; however, the evidence is not conclusive, and an equicausal status or even opposite causal direction is possible. Hence, malnutrition-inflammation complex syndrome (MICS) is an appropriate term. Possible causes of MICS include comorbid illnesses, oxidative and carbonyl stress, nutrient loss through dialysis, anorexia and low nutrient intake, uremic toxins, decreased clearance of inflammatory cytokines, volume overload, and dialysis-related factors. MICS is believed to be the main cause of erythropoietin hyporesponsiveness, high rate of cardiovascular atherosclerotic disease, decreased quality of life, and increased mortality and hospitalization in dialysis patients. Because MICS leads to a low body mass index, hypocholesterolemia, hypocreatininemia, and hypohomocysteinemia, a "reverse epidemiology" of cardiovascular risks can occur in dialysis patients. Therefore, obesity, hypercholesterolemia, and increased blood levels of creatinine and homocysteine appear to be protective and paradoxically associated with a better outcome. There is no consensus about how to determine the degree of severity of MICS or how to manage it. Several diagnostic tools and treatment modalities are discussed. Successful management of MICS may ameliorate the cardiovascular epidemic and poor outcome in dialysis patients. Clinical trials focusing on MICS and its possible causes and consequences are urgently required to improve poor clinical outcome in dialysis patients.
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                Author and article information

                Journal
                Int J Nephrol Renovasc Dis
                Int J Nephrol Renovasc Dis
                ijnrd
                ijnrd
                International Journal of Nephrology and Renovascular Disease
                Dove
                1178-7058
                20 January 2021
                2021
                : 14
                : 11-21
                Affiliations
                [1 ]Division of Nephrology, Hypertension and Kidney Transplantation, University of California, Irvine, School of Medicine , Orange, CA, USA
                [2 ]Department of Epidemiology, University of California, Los Angeles (UCLA) , Los Angeles, CA, USA
                [3 ]Los Angeles Biomedical Research Institute at Harbor–UCLA , Torrance, CA, USA
                [4 ]Fresenius Medical Care Renal Therapies Group , Waltham, MA, USA
                [5 ]Fresenius Kidney Care , Madison, WI, USA
                Author notes
                Correspondence: Kamyar Kalantar-Zadeh Division of Nephrology, Hypertension and Kidney Transplantation, University of California, Irvine Medical Center , 101 the City Drive South, Orange, CA92868-3217, USATel +1-714-456-5142Fax +1-714-456-6034 Email kkz@uci.edu
                Author information
                http://orcid.org/0000-0002-8666-0725
                http://orcid.org/0000-0003-3523-0028
                http://orcid.org/0000-0003-1880-5504
                http://orcid.org/0000-0003-0984-4544
                Article
                291348
                10.2147/IJNRD.S291348
                7829597
                33505168
                dba79239-424a-415d-a61c-f9584ff89285
                © 2021 Kalantar-Zadeh et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 10 November 2020
                : 30 December 2020
                Page count
                Figures: 4, Tables: 2, References: 81, Pages: 11
                Funding
                Funded by: Fresenius Medical Care Renal Therapies;
                Writing and editorial support funded by Fresenius Medical Care Renal Therapies Group.
                Categories
                Review

                Nephrology
                dialysis membrane,dialyzer,nutrition,hemodialysis,protein-energy wasting
                Nephrology
                dialysis membrane, dialyzer, nutrition, hemodialysis, protein-energy wasting

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