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      Performance of hemodialysis with novel medium cut-off dialyzers

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          Abstract

          Background. Compared to high-flux dialysis membranes, novel medium cut-off (MCO) membranes show greater permeability for larger middle molecules.

          Methods. In two prospective, open-label, controlled, randomized, crossover pilot studies, 39 prevalent hemodialysis (HD) patients were studied in four dialysis treatments as follows: study 1, three MCO prototype dialyzers (AA, BB and CC with increasing permeability) and one high-flux dialyzer in HD; and study 2, two MCO prototype dialyzers (AA and BB) in HD and high-flux dialyzers in HD and hemodiafiltration (HDF). Primary outcome was lambda free light chain (λFLC) overall clearance. Secondary outcomes included overall clearances and pre-to-post-reduction ratios of middle and small molecules, and safety of MCO HD treatments.

          Results. MCO HD provided greater λFLC overall clearance [least square mean (standard error)] as follows: study 1: MCO AA 8.5 (0.54), MCO BB 11.3 (0.51), MCO CC 15.0 (0.53) versus high-flux HD 3.6 (0.51) mL/min; study 2: MCO AA 10.0 (0.58), MCO BB 12.5 (0.57) versus high-flux HD 4.4 (0.57) and HDF 6.2 (0.58) mL/min. Differences between MCO and high-flux dialyzers were consistently significant in mixed model analysis (each P < 0.001). Reduction ratios of λFLC were greater for MCO. Clearances of α1-microglobulin, complement factor D, kappa FLC (κFLC) and myoglobin were generally greater with MCO than with high-flux HD and similar to or greater than clearances with HDF. Albumin loss was moderate with MCO, but greater than with high-flux HD and HDF.

          Conclusions. MCO HD removes a wide range of middle molecules more effectively than high-flux HD and even exceeds the performance of high-volume HDF for large solutes, particularly λFLC.

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          Most cited references37

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          MCO Membranes: Enhanced Selectivity in High-Flux Class

          Novel MCO high-flux membranes for hemodialysis have been developed with optimized permeability, allowing for filtration close to that of the natural kidney. A comprehensive in vitro characterization of the membrane properties by dextran filtration is presented. The sieving profile of pristine membranes, as well as that of membranes exposed to blood for 40 minutes, are described. The effective pore size (Stokes-Einstein radius) was estimated from filtration experiments before and after blood exposure, and results were compared to hydrodynamic radii of middle and large uremic toxins and essential proteins. The results indicate that the tailored pore sizes of the MCO membranes promote removal of large toxins while ensuring the retention of albumin.
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            Uremic Toxins and Their Effects on Multiple Organ Systems

            Nearly all body organs and systems are affected by the toxicity of uremic compounds retained in the course of renal dysfunction. Knowledge about the origin, chemical structure and composition of the retained endogenous substances responsible for these symptoms is far from complete. Organic retention solutes present a great variety of properties which makes their accurate classification extremely difficult. Their potential toxicity remains to be elucidated with meticulous observation of clearly formulated rules guiding the process. Toxicity assessment is a complex process because not just one but several retained compounds may be simultaneously involved in the same biological and metabolic processes. The search for new uremic compounds and combining them into panels of substances involved in the same pathophysiological processes seems to offer a novel approach to identifying and explaining any so far unexplored specific effects of endogenous compounds on the body organs and systems.
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              A comparison of on-line hemodiafiltration and high-flux hemodialysis: a prospective clinical study.

              Some of the morbidity associated with chronic hemodialysis is thought to result from retention of large molecular weight solutes that are poorly removed by diffusion in conventional hemodialysis. Hemodiafiltration combines convective and diffusive solute removal in a single therapy. The hypothesis that hemodiafiltration provides better solute removal than high-flux hemodialysis was tested in a prospective, randomized clinical trial. Patients were randomized to either on-line postdilution hemodiafiltration or high-flux hemodialysis. The groups did not differ in body size, treatment time, blood flow rate, or net fluid removal. The filtration volume in hemodiafiltration was 21 +/-1 L. Therapy prescriptions were unchanged for a 12-mo study period. Removal of both small (urea and creatinine) and large (ss(2)-microglobulin and complement factor D) solutes was significantly greater for hemodiafiltration than for high-flux hemodialysis. The increased urea and creatinine removal did not result in lower pretreatment serum concentrations in the hemodiafiltration group. Pretreatment plasma beta(2)-microglobulin concentrations decreased with time (P< 0.001); however, the decrease was similar for both therapies (P = 0.317). Pretreatment plasma complement factor D concentrations also decreased with time (P<0.001), and the decrease was significantly greater with hemodiafiltration than with high-flux hemodialysis (P = 0.010). The conclusion is that on-line hemodiafiltration provides superior solute removal to high-flux hemodialysis over a wide molecular weight range. The improved removal may not result in lower pretreatment plasma concentrations, however, possibly because of limitations in mass transfer rates within the body.
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                Author and article information

                Journal
                Nephrol Dial Transplant
                Nephrol. Dial. Transplant
                ndt
                Nephrology Dialysis Transplantation
                Oxford University Press
                0931-0509
                1460-2385
                January 2017
                01 September 2016
                01 September 2016
                : 32
                : 1
                : 165-172
                Affiliations
                [1 ]Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
                [2 ]Division of Nephrology, Department of Medicine, University Hospital, Würzburg, Germany
                [3 ]Gambro Lundia AB, Baxter Renal Therapeutic Area, Lund, Sweden
                [4 ]Gambro Dialysatoren GmbH, Baxter Renal Therapeutic Area, Hechingen, Germany
                [5 ]Baxter Healthcare Corporation, Life Science & Operations, Round Lake, IL, USA
                [6 ]Department of Internal Medicine, LKH Hochsteiermark, Bruck, Austria
                Author notes
                Correspondence and offprint requests to: Alexander H. Kirsch; E-mail: alexander.kirsch@ 123456medunigraz.at
                Article
                gfw310
                10.1093/ndt/gfw310
                5837492
                27587605
                4cd654c6-62c0-4b11-8428-95559d96a31f
                © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://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@oup.com

                History
                : 29 May 2016
                : 15 July 2016
                Page count
                Pages: 8
                Categories
                Original Articles
                CLINICAL SCIENCE
                Intra- and Extracorporeal Treatments of Kidney Failure

                Nephrology
                beta2-microglobulin,dialysis,hemodiafiltration,hemodialysis,uremic toxins
                Nephrology
                beta2-microglobulin, dialysis, hemodiafiltration, hemodialysis, uremic toxins

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