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      Elimination of Middle-Sized Uremic Solutes with High-Flux and High-Cut-Off Membranes: A Randomized in vivo Study

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          Abstract

          The elimination of substances between 10 and 50 kDa by conventional high-flux membranes is not satisfactory. We investigated in vivo the elimination of middle-sized uremic solutes by conventional polyflux (PF) and modified high-cut-off (HCO) membranes. All 12 patients underwent four treatments, two with the HCO dialyzer and two with the PF dialyzer, each in either a haemodialysis (HD) or haemodiafiltration (HDF) mode. The reduction ratio of urea, creatinine, β<sub>2</sub>-microglobulin (β<sub>2</sub>M), leptin, soluble TNF-RI, complement factor D, IL-6, sIL-6 receptor, advanced glycation end-products (AGEs) and albumin was determined. In addition, the amount removed was determined in the dialysate for β<sub>2</sub>M, complement factor D, AGEs and albumin. Treatment with HCO removed β<sub>2</sub>M, sTNF-RI, factor D, and high molecular AGE significantly better than conventional high-flux membranes. The albumin loss was higher when using HCO membranes. HCO membranes are a promising approach to improve removal of uremic toxins not affected by conventional high-flux membranes.

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          Inflammation in atherosclerosis: from pathophysiology to practice.

          Until recently, most envisaged atherosclerosis as a bland arterial collection of cholesterol, complicated by smooth muscle cell accumulation. According to that concept, endothelial denuding injury led to platelet aggregation and release of platelet factors which would trigger the proliferation of smooth muscle cells in the arterial intima. These cells would then elaborate an extracellular matrix that would entrap lipoproteins, forming the nidus of the atherosclerotic plaque. Beyond the vascular smooth muscle cells long recognized in atherosclerotic lesions, subsequent investigations identified immune cells and mediators at work in atheromata, implicating inflammation in this disease. Multiple independent pathways of evidence now pinpoint inflammation as a key regulatory process that links multiple risk factors for atherosclerosis and its complications with altered arterial biology. Knowledge has burgeoned regarding the operation of both innate and adaptive arms of immunity in atherogenesis, their interplay, and the balance of stimulatory and inhibitory pathways that regulate their participation in atheroma formation and complication. This revolution in our thinking about the pathophysiology of atherosclerosis has now begun to provide clinical insight and practical tools that may aid patient management. This review provides an update of the role of inflammation in atherogenesis and highlights how translation of these advances in basic science promises to change clinical practice.
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            Renal replacement therapy with high-cutoff hemofilters: Impact of convection and diffusion on cytokine clearances and protein status.

            High-cutoff hemofilters are characterized by an increased effective pore size designed to facilitate the elimination of inflammatory mediators in sepsis. This study compares diffusive versus convective high-cutoff renal replacement therapy (RRT) in terms of cytokine clearance rates and effects on plasma protein levels. Twenty-four patients with sepsis-induced acute renal failure were studied. A polyflux hemofilter with a cutoff point of approximately 60 kd was used for RRT. Patients were randomly allocated to either continuous venovenous hemofiltration (CVVH) with an ultrafiltration rate of 1 L/h (group 1) or 2.5 L/h (group 2) or continuous venovenous hemodialysis (CVVHD) with a dialysate flow rate of 1 L/h (group 3) or 2.5 L/h (group 4). Interleukin-1 (IL-1) receptor antagonist (IL-1ra), IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), and plasma proteins were measured daily. CVVH achieved significantly greater IL-1ra clearance compared with CVVHD (P = 0.0003). No difference was found for IL-6 (P = 0.935). Increasing ultrafiltration volume or dialysate flow led to a highly significant increase in IL-1ra and IL-6 clearance rates (P < 0.00001). Peak clearances were 46 mL/min for IL-1ra and 51 mL/min for IL-6. TNF-alpha clearance was poor for both RRT modalities. A significant decline in plasma IL-1ra and IL-6 clearance was observed in patients with high baseline levels. Protein and albumin losses were greatest during the 2.5-L/h hemofiltration mode. High-cutoff RRT is a novel strategy to clear cytokines more effectively. Convection has an advantage over diffusion in the clearance capacity of IL-1ra, but is associated with greater plasma protein losses.
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              Cytokine removal and cardiovascular hemodynamics in septic patients with continuous venovenous hemofiltration.

              To determine whether continuous venovenous hemofiltration leads to extraction of tumor necrosis factor alpha (TNF alpha) and cytokines from the circulation of critically ill patients with sepsis and acute renal failure and to quantitate the clearance and the removal rate of these cytokines and their effect on serum cytokine concentrations. Prospective, controlled study in patients with continuous venovenous hemofiltration (24 1/24 h) using a polysulphone membrane in patients with acute renal failure. 33 ventilated patients with acute renal failure of septic (n = 18) and cardiovascular origin (n = 15) were studied. Hemodynamic monitoring and collection of blood and ultrafiltrate samples before and during the first 72 h of continuous hemofiltration. Cardiovascular hemodynamics (Swan-Ganz catheter), Acute Physiology and Chronic Health Evaluation II score, creatinine, electrolytes, and blood urea nitrogen were recorded daily. Cytokines (TNF alpha, TNF alpha-RII, interleukin (IL) 1beta, IL1RA, IL2, IL2R, IL6, IL6R, IL8, IL10) were measured in prefilter blood and in ultrafiltrate immediately preceding and 12, 24, 48, and 72 h after initiating continuous venovenous hemofiltration (CVVH). Septic patients showed elevated cardiovascular values for cardiac output (7.2 +/- 2.1 l/min), cardiac index (4.2 +/- 1.3 l/min per m2), and stroke volume (67 +/- 23 ml) and reduced values for systemic vascular resistance (540 +/- 299 dyn x s x cm(-5)). All hemodynamic values normalized within the first 24 h after initiating CVVH treatment. TNF alpha was 1833 +/- 1217 pg/ml in septic patients and 42.9 +/- 6.3 pg/ml in nonseptic patients (p < 0.05) prior to CVVH. TNF alpha was detected in ultrafiltrate but did not decrease in blood during treatment with CVVH. There was no difference in IL 1beta between septic (3.8 +/- 1.9 pg/ml) and nonseptic patients (1.7 +/- 0.5 pg/ml). No significant elimination of cytokines was achieved in the present study by CVVH treatment. These findings demonstrate that CVVH can remove TNF alpha and special cytokines from the circulation of critically ill patients. Cardiovascular hemodynamics seemed to improve in septic patients after induction of hemofiltration treatment, although there was no evidence that extracorporeal removal of cytokines achieved a reduction in blood levels. The study indicates that low volume continuous hemofiltration with polysulphone membranes in patients with acute renal failure is not able to induce significant removal of cytokines.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2013
                January 2014
                20 December 2013
                : 36
                : 3-4
                : 287-294
                Affiliations
                aDepartment of Nephrology and Intensive Care Medicine, Universitätsmedizin Berlin, Charité Campus Virchow Clinic, Berlin, and bGambro Corporate Research, Hechingen, Germany
                Author notes
                *R. Schindler, MD, Department of Nephrology and Intensive Care Medicine, Charité Campus Virchow-Klinikum, Augustenburger Platz 1, DE-13353 Berlin (Germany), E-Mail ralf.schindler@charite.de
                Article
                356224 Blood Purif 2013;36:287-294
                10.1159/000356224
                24496201
                2be43373-1806-41af-82c4-f09c7666201c
                © 2013 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 05 March 2013
                : 04 October 2013
                Page count
                Figures: 4, Tables: 3, Pages: 8
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Modified high-cut-off membranes,Middle-sized uremic solutes,Uremic solutes, elimination ,Conventional polyflux membranes

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