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      Binding and detoxification efficiency of albumin decline after haemodialysis

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          ABSTRACT

          Background

          Albumin, as the most abundant plasma protein, represents a target structure for both drug and physicochemical therapeutic approaches to eliminate uraemic toxins more efficiently. Potentially, this approach could reduce mortality of haemodialysis patients. However, little is known about albumin functional properties in these patients and its alteration by haemodialysis treatment.

          Methods

          The binding and detoxification efficiency of albumin were assessed by electron paramagnetic resonance spectroscopy using a spin-labelled fatty acid. Binding efficiency (BE) reflects strength and amount of bound fatty acids under certain ethanol concentration. Detoxification efficiency (DTE) reflects the molecular flexibility of the patient's albumin molecule, thus the ability to change the conformation depending on ethanol concentration. Percentage of BE and DTE are depicted in relation to healthy individuals (100%).

          Results

          Fifty-eight patients (59% male, median age 68 years, median time on haemodialysis 32 months) were included in the study. Before haemodialysis treatment, albumin binding and detoxification efficiency were substantially below healthy individuals [median BE 52% (interquartile range, IQR, 45%–59%); median DTE 38% (IQR 32–49%)]. After haemodialysis treatment, median BE and DTE significantly decreased [BE 28% (IQR 20–41%); DTE 11% (IQR 7%–27%; P < .001)]. BE and DTE decline after haemodialysis was not dependent on age, sex or treatment modalities, but was to a certain extent on the level of non-esterified fatty acids.

          Conclusion

          Albumin binding and detoxification efficiency of fatty acids in maintenance haemodialysis patients were substantially below those in healthy individuals and even declined after dialysis treatment. These findings might be helpful when considering new therapeutic approaches in maintenance haemodialysis patients.

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          Most cited references27

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          Human serum albumin: from bench to bedside.

          Human serum albumin (HSA), the most abundant protein in plasma, is a monomeric multi-domain macromolecule, representing the main determinant of plasma oncotic pressure and the main modulator of fluid distribution between body compartments. HSA displays an extraordinary ligand binding capacity, providing a depot and carrier for many endogenous and exogenous compounds. Indeed, HSA represents the main carrier for fatty acids, affects pharmacokinetics of many drugs, provides the metabolic modification of some ligands, renders potential toxins harmless, accounts for most of the anti-oxidant capacity of human plasma, and displays (pseudo-)enzymatic properties. HSA is a valuable biomarker of many diseases, including cancer, rheumatoid arthritis, ischemia, post-menopausal obesity, severe acute graft-versus-host disease, and diseases that need monitoring of the glycemic control. Moreover, HSA is widely used clinically to treat several diseases, including hypovolemia, shock, burns, surgical blood loss, trauma, hemorrhage, cardiopulmonary bypass, acute respiratory distress syndrome, hemodialysis, acute liver failure, chronic liver disease, nutrition support, resuscitation, and hypoalbuminemia. Recently, biotechnological applications of HSA, including implantable biomaterials, surgical adhesives and sealants, biochromatography, ligand trapping, and fusion proteins, have been reported. Here, genetic, biochemical, biomedical, and biotechnological aspects of HSA are reviewed. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Albumin in decompensated cirrhosis: new concepts and perspectives

            The pathophysiological background of decompensated cirrhosis is characterised by a systemic proinflammatory and pro-oxidant milieu that plays a major role in the development of multiorgan dysfunction. Such abnormality is mainly due to the systemic spread of bacteria and/or bacterial products from the gut and danger-associated molecular patterns from the diseased liver triggering the release of proinflammatory mediators by activating immune cells. The exacerbation of these processes underlies the development of acute-on-chronic liver failure. A further mechanism promoting multiorgan dysfunction and failure likely consists with a mitochondrial oxidative phosphorylation dysfunction responsible for systemic cellular energy crisis. The systemic proinflammatory and pro-oxidant state of patients with decompensated cirrhosis is also responsible for structural and functional changes in the albumin molecule, which spoil its pleiotropic non-oncotic properties such as antioxidant, scavenging, immune-modulating and endothelium protective functions. The knowledge of these abnormalities provides novel targets for mechanistic treatments. In this respect, the oncotic and non-oncotic properties of albumin make it a potential multitarget agent. This would expand the well-established indications to the use of albumin in decompensated cirrhosis, which mainly aim at improving effective volaemia or preventing its deterioration. Evidence has been recently provided that long-term albumin administration to patients with cirrhosis and ascites improves survival, prevents complications, eases the management of ascites and reduces hospitalisations. However, variant results indicate that further investigations are needed, aiming at confirming the beneficial effects of albumin, clarifying its optimal dosage and administration schedule and identify patients who would benefit most from long-term albumin administration.
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              Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality.

              Albumin concentration is diminished in patients with liver failure. Albumin infusion improves survival of cirrhotic patients with spontaneous bacterial peritonitis, and it is hypothesized that this may be due in part to its detoxifying capabilities. The aim of this study was to perform detailed quantitative and qualitative assessment of albumin function in patients with cirrhosis. Healthy controls and patients with acute deterioration of cirrhosis requiring hospital admission (n = 34) were included. Albumin function was assessed using affinity of the fatty acid binding sites using a spin label (16 doxyl-stearate) titration and electron paramagnetic resonance spectroscopy and ischemia-modified albumin (IMA) was measured. Twenty-two patients developed acute-on-chronic liver failure. Twelve were treated with the Molecular Adsorbents Recirculating System (MARS) and 10 with standard medical therapy. For each parameter measured, the patients' albumin had reduced functional ability, which worsened with disease severity. Fifteen patients died, and IMA, expressed as an albumin ratio (IMAR), was significantly higher in nonsurvivors compared with survivors (P < 0.001; area under the receiver operating curve = 0.8). No change in the patients' albumin function was observed following MARS therapy. A significant negative correlation between IMAR and the fatty acid binding coefficients for sites 1 and 2 (P < 0.001 for both) was observed, indicating possible sites of association on the protein. The results of this study suggests marked dysfunction of albumin function in advanced cirrhosis and provide further evidence for damage to the circulating albumin, which is not reversed by MARS therapy. IMAR correlates with disease severity and may have prognostic use in acute-on-chronic liver failure.
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                Author and article information

                Contributors
                Journal
                Nephrol Dial Transplant
                Nephrol Dial Transplant
                ndt
                Nephrology Dialysis Transplantation
                Oxford University Press
                0931-0509
                1460-2385
                February 2024
                09 August 2023
                09 August 2023
                : 39
                : 2
                : 215-221
                Affiliations
                Department of Nephrology, University Hospital Essen, University Duisburg-Essen , Essen, Germany
                MedInnovation GmbH , Berlin, Germany
                MedInnovation GmbH , Berlin, Germany
                Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz , Graz, Austria
                Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University Duisburg-Essen , Essen, Germany
                Gemeinschaftspraxis für Nieren- und Hochdruckkrankheiten Essen-Steele , Essen, Germany
                Dialyse- und Lipid-Zentrum Nordrhein , Essen, Germany
                Dialyse- und Lipid-Zentrum Nordrhein , Essen, Germany
                Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz , Graz, Austria
                Department of Nephrology, University Hospital Essen, University Duisburg-Essen , Essen, Germany
                Author notes
                Correspondence to: Kristina Boss; E-mail: kristina.boss@ 123456uk-essen.de

                These authors contributed equally to the manuscript.

                Article
                gfad133
                10.1093/ndt/gfad133
                10828194
                37558390
                926824f5-599e-41c9-9d85-31041619e73e
                © The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 19 March 2023
                : 18 August 2023
                Page count
                Pages: 7
                Funding
                Funded by: Stiftung Universitätsmedizin Essen, DOI 10.13039/501100010380;
                Award ID: 2022 4699 112
                Categories
                Original Article
                AcademicSubjects/MED00340

                Nephrology
                albumin,binding capacity,electron paramagnetic resonance,haemodialysis,spin-probe technique

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