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      Use of Ultrapure Dialysate in Reduction of Chronic Inflammation during Hemodialysis

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          Abstract

          Chronic inflammation contributes to the pathogenesis of several complications of hemodialysis therapy. It is thought that backfiltration of bacteria-derived contaminations during dialysis may induce a chronic inflammatory state. High-sensitivity C-reactive protein (hs-CRP) is one of the tools which can take a hold on such a chronic inflammatory condition. We examined the effect of ultrapure dialysate which contributes to chronic inflammation with hs-CRP and tried to reduce endotoxin (ET) levels at the end of the dialysate from 70 EU/l to <1.0 EU/l (ultrapure dialysate). Other dialysis conditions, except ET level, were fixed. We investigated the hs-CRP of 23 patients receiving regular dialysis before the use of ultrapure dialysate and 1 year after use of it prospectively. The data showed a significant decrease in the median value of the hs-CRP from 0.16 to 0.07 mg/dl (p < 0.05). The value of serum β<sub>2</sub>-microglobulin decreased from 33.2 to 28.4 mg/dl (p < 0.01) and the hemoglobin level increased from 10.0 to 11.0 g/dl (p < 0.05). These results indicate that even a dialysate containing 70 EU/l of ET level may induce a chronic inflammatory state. hs-CRP is a very useful marker of chronic inflammation and the use of ultrapure dialysate is necessary to improve a chronic inflammatory state. The targeted ET level at the end of the dialysate should be set at ≤1.0 EU/l.

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          Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure.

          Atherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. C-reactive protein (CRP), an acute-phase protein, is a predictor of cardiovascular mortality in nonrenal patient populations. In chronic renal failure (CRF), the prevalence of an acute-phase response has been associated with an increased mortality. One hundred and nine predialysis patients (age 52 +/- 1 years) with terminal CRF (glomerular filtration rate 7 +/- 1 ml/min) were studied. By using noninvasive B-mode ultrasonography, the cross-sectional carotid intima-media area was calculated, and the presence or absence of carotid plaques was determined. Nutritional status was assessed by subjective global assessment (SGA), dual-energy x-ray absorptiometry (DXA), serum albumin, serum creatinine, serum urea, and 24-hour urine urea excretion. The presence of an inflammatory reaction was assessed by CRP, fibrinogen (N = 46), and tumor necrosis factor-alpha (TNF-alpha; N = 87). Lipid parameters, including Lp(a) and apo(a)-isoforms, as well as markers of oxidative stress (autoantibodies against oxidized low-density lipoprotein and vitamin E), were also determined. Compared with healthy controls, CRF patients had an increased mean carotid intima-media area (18.3 +/- 0.6 vs. 13.2 +/- 0.7 mm2, P or = 10 mg/liter). Malnourished patients had higher CRP levels (23 +/- 3 vs. 13 +/- 2 mg/liter, P < 0.01), elevated calculated intima-media area (20.2 +/- 0.8 vs. 16.9 +/- 0.7 mm2, P < 0.01) and a higher prevalence of carotid plaques (90 vs. 60%, P < 0.0001) compared with well-nourished patients. During stepwise multivariate analysis adjusting for age and gender, vitamin E (P < 0.05) and CRP (P < 0.05) remained associated with an increased intima-media area. The presence of carotid plaques was significantly associated with age (P < 0.001), log oxidized low-density lipoprotein (oxLDL; P < 0.01), and small apo(a) isoform size (P < 0.05) in a multivariate logistic regression model. These results indicate that the rapidly developing atherosclerosis in advanced CRF appears to be caused by a synergism of different mechanisms, such as malnutrition, inflammation, oxidative stress, and genetic components. Apart from classic risk factors, low vitamin E levels and elevated CRP levels are associated with an increased intima-media area, whereas small molecular weight apo(a) isoforms and increased levels of oxLDL are associated with the presence of carotid plaques.
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            Serum C-reactive protein (CRP) and risk of death in chronic dialysis patients.

            The prognosis of chronic dialysis patients is poor, in part due to the high incidence of cardiovascular disease. Malnutrition, such as hypoalbuminaemia, has been shown to be a predictor of death in this group of patients, while serum C-reactive protein (CRP) is a predictor of myocardial infarction and sudden death. Thus, the aim of the present study was to determine of the relationship between CRP and serum albumin concentration, and the value of baseline CRP data in the prediction of death. In one of the dialysis units in Okinawa, Japan, baseline CRP data was available (n=163, 95 men and 68 women) in January 1991. These patients were divided into two groups according to their baseline CRP levels, with group 1 consisting of CRP or =10 mg/l (n=35), and then followed up until the end of 1997. Survival curves were calculated using the Kaplan-Meier method. The statistical significance of the relationship between CRP levels and the risk of death was evaluated by multiple logistic analysis with covariables such as age, sex, diabetes mellitus, serum albumin, and blood pressure. The mean (SD) level of serum albumin was 38 (3) g/l in group 1 and 36 (3) g/l in group 2 (P<0.00001). The 5-year survival rate was significantly poorer in group 2 (44.4%) than in group 1 (82.5%) (P<0.0001). Furthermore, the risk of death was significantly higher in group 2 (relative risk 3.48 (95% confidence interval 1.76-6.89), P<0.0003) by multivariate Cox proportional hazard analysis. CRP is a significant predictor of death in chronic dialysis patients, independent of serum albumin and other possible confounders. Dialysis patients with high CRP levels should be carefully evaluated and monitored regardless of serum albumin concentrations in the normal range.
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              Ultrapure Dialysate Reduces Dose of Recombinant Human Erythropoietin

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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
                : 26-29
                Affiliations
                Department of Nephrology, Kumamoto Chuo Hospital, Kumamoto, Japan
                Article
                81870 Blood Purif 2004;22(suppl 2):26–29
                10.1159/000081870
                15655319
                775e2474-6205-49f0-a4d3-1c9233b2a41e
                © 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: 5, References: 8, Pages: 4
                Categories
                Symposium

                Cardiovascular Medicine,Nephrology
                High-sensitivity C-reactive protein,Chronic inflammation,Ultrapure dialysate,Endotoxin levels

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