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      About Blood Purification: 3.0 Impact Factor I 5.6 CiteScore I 0.83 Scimago Journal & Country Rank (SJR)

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      Effect of Hemodiafiltration against Radical Stress in the Course of Blood Purification

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          Abstract

          The involvement of radical stress has been suggested as a cause for complications in patients on dialysis, such as arteriosclerosis, dialysis-related amyloidosis, etc. It has been reported that the increase in radical stress is not only seen in renal failure, but that its amplified effect is also seen in the process of blood purification. Our group has reported on the radical stress-reducing effect of HDF. We performed four types of blood purification (HD; on-line HDF; pre, on-line HDF; post, P/P HDF) in patients on maintenance dialysis using the polysulfone (APS) dialyzer. The change in radical related markers such as pentosidine (total, free) and CML (total, free), and the CTL/Cr ratio, and the hydroperoxide radicals were studied. In HDF (post, pre), the amplification rate of hydroperoxide radicals was significantly low, whereas the reduction rate of CTL/Cr ratio as index for hydroxy radicals was significantly higher in on-line HDF than in HD. Both the total CML and T-pentosidine increased in HD but showed a decrease in HDF. As HDF uses large amounts of replacement solution, the following effects can be expected: (a) suppression of the amplification of hydroperoxide radicals and suppression of the amplification of hydroxy radicals, and (b) suppression of fat oxidation by AGEs themselves. These antiradical stress effects are presumed to be exerted by effective removal of radical carrier protein, denatured protein, and complement protein in HDF, by dilution of radicals by massive use of replacement solution, and by the sequential reduction of the excitation and amplification effects.

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          Most cited references8

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          Lipid advanced glycosylation: pathway for lipid oxidation in vivo.

          To address potential mechanisms for oxidative modification of lipids in vivo, we investigated the possibility that phospholipids react directly with glucose to form advanced glycosylation end products (AGEs) that then initiate lipid oxidation. Phospholipid-linked AGEs formed readily in vitro, mimicking the absorbance, fluorescence, and immunochemical properties of AGEs that result from advanced glycosylation of proteins. Oxidation of unsaturated fatty acid residues, as assessed by reactive aldehyde formation, occurred at a rate that paralleled the rate of lipid advanced glycosylation. Aminoguanidine, an agent that prevents protein advanced glycosylation, inhibited both lipid advanced glycosylation and oxidative modification. Incubation of low density lipoprotein (LDL) with glucose produced AGE moieties that were attached to both the lipid and the apoprotein components. Oxidized LDL formed concomitantly with AGE-modified LDL. Of significance, AGE ELISA analysis of LDL specimens isolated from diabetic individuals revealed increased levels of both apoprotein- and lipid-linked AGEs when compared to specimens obtained from normal, nondiabetic controls. Circulating levels of oxidized LDL were elevated in diabetic patients and correlated significantly with lipid AGE levels. These data support the concept that AGE oxidation plays an important and perhaps primary role in initiating lipid oxidation in vivo.
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            Renal filtration and catabolism of complement protein D.

            Complement protein D, a serine protease participating in the formation of the C3 convertase of the alternative complement pathway, has the lowest molecular weight (23,750) and serum concentration of all complement proteins. In normal serum, D is the rate-limiting protease of the alternative pathway of complement activation. We report that the serum concentrations of D in 20 patients with chronic renal failure (mean +/- S.D., 0.42 +/- 0.28 mg per deciliter) and in 16 patients on long-term dialysis (1.53 +/- 0.39 mg per deciliter) were significantly higher (P less than 0.001) than in 22 healthy adults (0.18 +/- 0.04 mg per deciliter). In chronic renal failure the serum concentration of D correlated with that of creatinine (r = 0.75, P less than 0.001). The serum concentrations of D found in patients with renal failure reached and in some cases exceeded those at which the protease is no longer rate-limiting. Thus, enhanced activity of the alternative pathway of complement should be expected in patients with advanced renal failure. Urinary D was undetectable (less than 0.2 micrograms per deciliter) in 17 normal adults and either undetectable or below the concentration expected from the degree of proteinuria in 10 patients with nephrotic syndrome. However, in a patient with Fanconi's syndrome the urinary concentration of D (1.3 mg per deciliter) was an order of magnitude higher than the serum concentration, representing 0.5 per cent of the total protein. The urinary D in this patient had normal hemolytic activity, antigenicity, and size. These results indicate that D is filtered through the glomerular membrane and is probably catabolized in the proximal renal tubules.
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              Role of iron in the tubulo-interstitial injury in nephrotoxic serum nephritis.

              We studied the possibility that tubule fluid iron could be involved in the pathogenesis of the tubulo-interstitial injury associated with primary glomerular disease. Tubule fluid iron is determined by the magnitude of the glomerular leak for transferrin and the iron saturation of transferrin. To minimize tubule fluid iron in an experimental model of glomerulonephritis, iron deficiency was induced in rats prior to the induction of nephrotoxic serum nephritis. Iron deficiency did not effect the development of glomerular disease as determined by proteinuria, but had a marked effect on preventing the development of tubulo-interstitial disease and renal functional deterioration. There was also a strong correlation between the amount of functional deterioration and extent of tubulo-interstitial disease and urinary iron excretion in both the control and iron deficient animals. It is proposed that injury results from iron being dissociated from transferrin at the more acid pH of the tubule fluid. Iron, a transition element, is able to catalyze the Haber-Weiss reaction with the formation of free hydroxyl radicals which causes renal tubule cell injury. This tubulo-interstitial injury is the major determinate of progressive renal functional deterioration in this experimental model of glomerulonephritis.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                978-3-8055-7886-8
                978-3-318-01189-0
                0253-5068
                1421-9735
                2004
                January 2005
                27 January 2005
                : 22
                : Suppl 2
                : 72-77
                Affiliations
                Second Department of Internal Medicine, Oita University, Faculty of Medicine, Hazama, Japan
                Article
                81879 Blood Purif 2004;22(suppl 2):72–77
                10.1159/000081879
                15655328
                0ed0b60f-5063-4799-95f0-f1a537efcd03
                © 2004 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
                Page count
                Figures: 8, References: 13, Pages: 6
                Categories
                Luncheon Seminar

                Cardiovascular Medicine,Nephrology
                Advanced glycation end products,Hydroperoxide radical,Hemodiafiltration,Hydroxy radical

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