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      Proteomic Investigations into Hemodialysis Therapy

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          Abstract

          The retention of a number of solutes that may cause adverse biochemical/biological effects, called uremic toxins, characterizes uremic syndrome. Uremia therapy is based on renal replacement therapy, hemodialysis being the most commonly used modality. The membrane contained in the hemodialyzer represents the ultimate determinant of the success and quality of hemodialysis therapy. Membrane’s performance can be evaluated in terms of removal efficiency for unwanted solutes and excess fluid, and minimization of negative interactions between the membrane material and blood components that define the membrane’s bio(in)compatibility. Given the high concentration of plasma proteins and the complexity of structural functional relationships of this class of molecules, the performance of a membrane is highly influenced by its interaction with the plasma protein repertoire. Proteomic investigations have been increasingly applied to describe the protein uremic milieu, to compare the blood purification efficiency of different dialyzer membranes or different extracorporeal techniques, and to evaluate the adsorption of plasma proteins onto hemodialysis membranes. In this article, we aim to highlight investigations in the hemodialysis setting making use of recent developments in proteomic technologies. Examples are presented of why proteomics may be helpful to nephrology and may possibly affect future directions in renal research.

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          Most cited references78

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          Surface exposure of phosphatidylserine in pathological cells.

          The asymmetric phospholipid distribution in plasma membranes is normally maintained by energy-dependent lipid transporters that translocate different phospholipids from one monolayer to the other against their respective concentration gradients. When cells are activated, or enter apoptosis, lipid asymmetry can be perturbed by other lipid transporters (scramblases) that shuttle phospholipids non-specifically between the two monolayers. This exposes phosphatidylserine (PS) at the cells' outer surface. Since PS promotes blood coagulation, defective scramblase activity upon platelet stimulation causes a bleeding disorder (Scott syndrome). PS exposure also plays a pivotal role in the recognition and removal of apoptotic cells via a PS-recognizing receptor on phagocytic cells. Furthermore, expression of PS at the cell surface can occur in a wide variety of disorders. This review aims at highlighting how PS expression in different cells may complicate a variety of pathological conditions, including those that promote thromboembolic complications or produce aberrations in apoptotic cell removal.
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            Uremic toxins originating from colonic microbial metabolism.

            Numerous molecules, which are either excreted or metabolized by the kidney, accumulate in patients with chronic kidney disease (CKD). These uremic retention molecules (URMs), contributing to the syndrome of uremia, may be classified according to their site of origin, that is, endogenous metabolism, microbial metabolism, or exogenous intake. It is increasingly recognized that bacterial metabolites, such as phenols, indoles, and amines, may contribute to uremic toxicity. In vitro studies have implicated bacterial URMs in CKD progression, cardiovascular disease, and bone and mineral disorders. Furthermore, several observational studies have demonstrated a link between serum levels of bacterial URMs and clinical outcomes. Bacterial metabolism may therefore be an important therapeutic target in CKD. There is evidence that besides reduced renal clearance, increased colonic generation and absorption explain the high levels of bacterial URMs in CKD. Factors promoting URM generation and absorption include an increased ratio of dietary protein to carbohydrate due to insufficient intake of fiber and/or reduced intestinal protein assimilation, as well as prolonged colonic transit time. Two main strategies exist to reduce bacterial URM levels: interventions that modulate intestinal bacterial growth (e.g., probiotics, prebiotics, dietary modification) and adsorbent therapies that bind bacterial URMs in the intestines to reduce their absorption (e.g., AST-120, sevelamer). The efficacy and clinical benefit of these strategies are currently an active area of interest.
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              How smart do biomaterials need to be? A translational science and clinical point of view.

              Over the last 4 decades innovations in biomaterials and medical technology have had a sustainable impact on the development of biopolymers, titanium/stainless steel and ceramics utilized in medical devices and implants. This progress was primarily driven by issues of biocompatibility and demands for enhanced mechanical performance of permanent and non-permanent implants as well as medical devices and artificial organs. In the 21st century, the biomaterials community aims to develop advanced medical devices and implants, to establish techniques to meet these requirements, and to facilitate the treatment of older as well as younger patient cohorts. The major advances in the last 10 years from a cellular and molecular knowledge point of view provided the scientific foundation for the development of third-generation biomaterials. With the introduction of new concepts in molecular biology in the 2000s and specifically advances in genomics and proteomics, a differentiated understanding of biocompatibility slowly evolved. These cell biological discoveries significantly affected the way of biomaterials design and use. At the same time both clinical demands and patient expectations continued to grow. Therefore, the development of cutting-edge treatment strategies that alleviate or at least delay the need of implants could open up new vistas. This represents the main challenge for the biomaterials community in the 21st century. As a result, the present decade has seen the emergence of the fourth generation of biomaterials, the so-called smart or biomimetic materials. A key challenge in designing smart biomaterials is to capture the degree of complexity needed to mimic the extracellular matrix (ECM) of natural tissue. We are still a long way from recreating the molecular architecture of the ECM one to one and the dynamic mechanisms by which information is revealed in the ECM proteins in response to challenges within the host environment. This special issue on smart biomaterials lists a large number of excellent review articles which core is to present and discuss the basic sciences on the topic of smart biomaterials. On the other hand, the purpose of our review is to assess state of the art and future perspectives of the so called "smart biomaterials" from a translational science and specifically clinical point of view. Our aim is to filter out and discuss which biomedical advances and innovations help us to achieve the objective to translate smart biomaterials from bench to bedside. The authors predict that analyzing the field of smart biomaterials from a clinical point of view, looking back 50 years from now, it will show that this is our heritage in the 21st century. Copyright © 2012 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                10 December 2015
                December 2015
                : 16
                : 12
                : 29508-29521
                Affiliations
                [1 ]Nephrology and Dialysis Institute, Department of Medicine, G. d’Annunzio University, Chieti-Pescara, SS. Annunziata Hospital, Via dei Vestini, 66013 Chieti, Italy; vsirolli@ 123456unich.it (V.S.); p.felaco@ 123456gmail.com (P.F.); lamoroso@ 123456unich.it (L.A.)
                [2 ]Proteomics and Metabonomics Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) S. Lucia Foundation, 00179 Rome, Italy; luisa.pieroni@ 123456uniroma2.it (L.P.); andrea.urbani@ 123456uniroma2.it (A.U.)
                [3 ]Department of Surgery and Experimental Medicine, Tor Vergata University, 00134 Rome, Italy
                Author notes
                [* ]Correspondence: m.bonomini@ 123456nephro.unich.it ; Tel.: +39-0871-540120; Fax: +39-0871-574736
                Article
                ijms-16-26189
                10.3390/ijms161226189
                4691132
                26690416
                0a6e24d3-7476-440d-8109-4fb6cb84bee3
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 October 2015
                : 02 December 2015
                Categories
                Review

                Molecular biology
                proteomic,hemodialysis,uremic toxins,biocompatibility,dialysis membrane
                Molecular biology
                proteomic, hemodialysis, uremic toxins, biocompatibility, dialysis membrane

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