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      Assessment of Inflow of Endotoxin and Its Fragments in Patients on Maintenance Hemodialysis

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          Abstract

          Background: We estimated the flow of endotoxins (ET) from dialysates into the blood of patients on hemodialysis (HD) using limulus amebocyte lysate (LAL) assays and endotoxin activity (EA) determined by neutrophil respiratory burst activity. Methods: A cross-sectional study compared groups given ultrapure bicarbonate (n = 15; group A), acetate-free bicarbonate dialysates (n = 20; group B) and conventional bicarbonate dialysate (n = 23; group C). A prospective study of group C examined the effect of changing the purity of the dialysate. Biomarkers of inflammation and oxidative stress were measured and ET in blood was assessed by LAL assays and EA. Results: Serum ET levels did not differ among the groups, whereas EA and the biomarkers were significantly increased in group C compared with those in groups A and B. HD using conventional dialysate was independently associated with an increase in EA. Purifying the dialysate significantly decreased EA in group C. Conclusion: Measuring EA is useful to assess the influence of dialysate contamination in HD patients.

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          Aspects of immune dysfunction in end-stage renal disease.

          End-stage renal disease (ESRD) is associated with significantly increased morbidity and mortality resulting from cardiovascular disease (CVD) and infections, accounting for 50% and 20%, respectively, of the total mortality in ESRD patients. It is possible that these two complications are linked to alterations in the immune system in ESRD, as uremia is associated with a state of immune dysfunction characterized by immunodepression that contributes to the high prevalence of infections among these patients, as well as by immunoactivation resulting in inflammation that may contribute to CVD. This review describes disorders of the innate and adaptive immune systems in ESRD, underlining the specific role of ESRD-associated disturbances of Toll-like receptors. Finally, based on the emerging links between the alterations of immune system, CVD, and infections in ESRD patients, it emphasizes the potential role of the immune dysfunction in ESRD as an underlying cause for the high mortality in this patient population and the need for more studies in this area.
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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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              Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study.

              A novel assay for endotoxin, based on the ability of antigen-antibody complexes to prime neutrophils for an augmented respiratory burst response, was studied in a cohort study of 857 patients admitted to an intensive-care unit (ICU). On the day of ICU admission, 57.2% of patients had either intermediate (>or=0.40 endotoxin activity [EA] units) or high (>or=0.60 units) EA levels. Gram-negative infection was present in 1.4% of patients with low EA levels, 4.9% with intermediate levels, and 6.9% with high levels; EA had a sensitivity of 85.3% and a specificity of 44.0% for the diagnosis of gram-negative infection. Rates of severe sepsis were 4.9%, 9.2%, and 13.2%, and ICU mortality was 10.9%, 13.2%, and 16.8% for patients with low, intermediate, and high EA levels, respectively. Stepwise logistic regression analysis showed that elevated Acute Physiology and Chronic Health Evaluation II score, gram-negative infection, and emergency admission status were independent predictors of EA.
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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
                2011
                June 2011
                13 January 2011
                : 31
                : 4
                : 268-275
                Affiliations
                aDivision of Nephrology, Department of Medicine, Showa University School of Medicine, and bEbara Clinic, Tokyo, and cKawasaki Clinic, Kawasaki, Japan
                Author notes
                *Hirokazu Honda, MD, PhD, Division of Nephrology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666 (Japan), Tel. +81 3 3784 8533, Fax +81 3 3784 5934, E-Mail hondah@med.showa-u.ac.jp
                Article
                322622 Blood Purif 2011;31:268–275
                10.1159/000322622
                21242680
                00a65d46-680a-418e-8d10-d6bcae9efbdf
                © 2011 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
                : 21 May 2010
                : 03 November 2010
                Page count
                Figures: 3, Tables: 3, Pages: 8
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Endotoxin,Maintenance hemodialysis,End-stage renal disease
                Cardiovascular Medicine, Nephrology
                Endotoxin, Maintenance hemodialysis, End-stage renal disease

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