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      Reduction of Free Immunoglobulin Light Chains Using Adsorption Properties of Hemodiafiltration with Endogenous Reinfusion

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          Abstract

          In this work we investigated the acute effects of hemodiafiltration with endogenous reinfusion (HFR therapy) on the removal of free immunoglobulin light chains (FIgLCs), which may be considered members of the family of uremic toxins. In two groups of patients – group 1 (polyclonal FIgLCs production) and group 2 (monoclonal plasma cell proliferative disorders), we analyzed the pre- and postdialysis levels of ĸ- and λ-chains. In group 1 we observed a significant reduction of FIgLCs (p < 0.01). A similar trend was found in patients of group 2 only for ĸ-chains. The FIgLCs removal ratio was significantly higher for ĸ- than λ-chains in the two patient groups. In vitro data showed affinity of macroporous resin to binding FIgLCs. Our results show that the HFR therapy could be effective in removing FIgLCs, particularly ĸ-chains in dialysis patients with polyclonal and monoclonal FIgLCs production.

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          Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies.

          Of patients with newly diagnosed multiple myeloma, approximately 10% have dialysis-dependent acute renal failure, with cast nephropathy, caused by monoclonal free light chains (FLC). Of these, 80 to 90% require long-term renal replacement therapy. Early treatment by plasma exchange reduces serum FLC concentrations, but randomized, controlled trials have shown no evidence of renal recovery. This outcome can be explained by the low efficiency of the procedure. A model of FLC production, distribution, and metabolism in patients with myeloma indicated that plasma exchange might remove only 25% of the total amount during a 3-wk period. For increasing FLC removal, extended hemodialysis with a protein-leaking dialyzer was used. In vitro studies indicated that the Gambro HCO 1100 dialyzer was the most efficient of seven tested. Model calculations suggested that it might remove 90% of FLC during 3 wk. This dialyzer then was evaluated in eight patients with myeloma and renal failure. Serum FLC reduced by 35 to 70% within 2 hr, but reduction rates slowed as extravascular re-equilibration occurred. FLC concentrations rebounded on successive days unless chemotherapy was effective. Five additional patients with acute renal failure that was caused by cast nephropathy then were treated aggressively, and three became dialysis independent. A total of 1.7 kg of FLC was removed from one patient during 6 wk. Extended hemodialysis with the Gambro HCO 1100 dialyzer allowed continuous, safe removal of FLC in large amounts. Proof of clinical value now will require larger studies.
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            Effect of haemodiafiltration with online regeneration of ultrafiltrate on oxidative stress in dialysis patients.

            Increased oxidative stress (OxSt) as well as inflammation are risk factors for cardiovascular events and determinant of cardiovascular disease which remains the most common cause of excess morbidity and mortality for end-stage renal disease ESRD patients. Haemodiafiltration with on-line regeneration of ultrafiltrate (HFR) has been shown to have a positive impact on markers of inflammation while its effect on OxSt is not known. This study evaluates in haemodialysis patients the effect of HFR on the plasma level of oxidized LDL (OxLDL), a marker of OxSt, and mononuclear cell gene and protein expression of OxSt-related proteins such as p22phox (subunit of NAD(P)H oxidase), PAI-1 (induced by OxSt and atherothrombogenetic) and haeme-oxygenase-1 (HO-1) (induced by OxSt). Fourteen patients were randomized into two groups in a crossover design, treated for 6 month periods with HFR (SG8 Plus-Bellco, Mirandola, Italy) or low-flux bicarbonate dialysis (HD) using a polysulphone dialyser 1.8 m2. Blood samples were collected at the beginning of the study, after 6 months (crossover) and after 12 months. ANOVA analysis of the data performed to rule out any crossover effect in either sequence was not significant and thus data from both sequences were combined and then analysed further statistically. HFR reduced mRNA production and protein expression of p22phox and PAI-1 compared with HD (-9+/-5 vs 2+/-6 Delta%, P<0.0001 and -15+/-20 vs 3+/-17 Delta%, P<0.05 for p22phox; -19+/-6 vs -5+/-5 Delta%, P<0.0001 and -24+/-12 vs 9+/-15 Delta%, P<0.0001 for PAI-1). HO-1 was unchanged (-12+/-8 vs -10+/-8 Delta% and -21+/-12 vs -14+/-8 Delta%) while plasma OxLDL was reduced (-14+/-19 vs 1+/-14 Delta%, P<0.01). The results of our study indicate that HFR treatment, compared with standard dialysis, has a lower impact on OxSt. Given, the strong relationship between OxSt and inflammation and their impact on the long-term cardiovascular complications in end-stage renal disease patients, HFR might have a more beneficial impact in reducing the risk of atherosclerotic cardiovascular disease in dialysis patients.
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              Effect of dialysis on serum/plasma levels of free immunoglobulin light chains in end-stage renal disease patients.

              Free immunoglobulin light chains (FLCs) have previously been shown to be uraemic toxins. In this work we investigated the effect of haemodialysis and haemodiafiltration on the level of FLCs in serum/plasma of uraemic patients. Serum/plasma proteins were separated by non-reducing SDS-PAGE and transferred to a nitro-cellulose membrane. FLCs were detected by specific antibodies and an enhanced chemiluminescence detection system. The FLC concentrations were calculated. We studied 15 healthy subjects, 10 patients with chronic renal failure, 71 patients undergoing haemodialysis treatment and 33 patients treated with haemodiafiltration. Different membranes were compared: low- and high-flux polysulfone membranes, low- and high-flux cellulose triacetate membranes, high-flux polymethylmethacrylate and polyacrylonitrile membranes. Chronic renal failure patients showed elevated FLC concentrations as compared with controls. In haemodialysis or haemodiafiltration patients these values were even higher. This was mainly due to an increased concentration of FLC of the lambda-type. The treatment modality per se did not influence the FLC concentrations. Only haemodialysis or haemodiafiltration with the polymethylmethacrylate membrane lead to a significant reduction in FLC concentrations; however, these did not reach control levels. We did not observe differences in FLC levels between patients with different underlying diseases, nor did we find a correlation between age or the duration of the dialysis treatment and FLC concentrations. We found a positive correlation between FLC concentrations at the beginning of dialysis treatment and the amount of IgLCs removed during treatment. However, the average FLC level after treatment did not reach control values. Currently available haemodialysis or haemodiafiltration treatments are unable to normalize the elevated serum/plasma levels of FLCs in end-stage renal disease patients.
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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
                2010
                July 2010
                24 June 2010
                : 30
                : 1
                : 34-36
                Affiliations
                aExpansion Centres d’Hémodialyse de l’Ouest et bLaboratoire de Biochimie Spécialisée, CHU, Nantes, France; cScientific Affairs Department, Sorin Group, Mirandola, Italy
                Article
                316684 Blood Purif 2010;30:34–36
                10.1159/000316684
                20588010
                7aff63b0-67f2-44fb-9965-4e4df77dad19
                © 2010 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
                : 18 May 2009
                : 11 April 2010
                Page count
                Figures: 2, References: 8, Pages: 3
                Categories
                Technical Note

                Cardiovascular Medicine,Nephrology
                Macroporous resin,Adsorption,Hemodiafiltration,Uremic toxins,Free immunoglobulin light chains,Hemodiafiltration with endogenous reinfusion

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