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      Interleukin-1 Gene Cluster Polymorphisms Are Associated with Nutritional Status and Inflammation in Patients with End-Stage Renal Disease

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          Abstract

          Background: Wasting and inflammation are two common risk factors for death in patients with end-stage renal disease (ESRD). Interleukin-1β (IL-1β) and its receptor antagonist (IL-1Ra) may play a pivotal role in the pathogenesis of wasting and inflammation. Methods: To investigate effects of the IL-1 gene cluster polymorphisms on wasting and inflammation, we studied 189 ESRD patients (52 ± 12 years, 62% males) close to the start of renal replacement therapy. 205 healthy volunteers served as controls. We analyzed the IL-1B –511C/T, –31C/T, and +3954C/T polymorphisms as well as a variable number of a tandem repeat (VNTR) in IL-1RN. Nutritional parameters included serum albumin level, subjective global nutritional assessment (SGA), and body composition evaluated by dual-energy X-ray absorptiometry (DXA). We used serum high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation. Results: Wasting (SGA >1) was present in 31%, whereas inflammation (CRP ≧10 mg/l) was present in 36% of the patients. The male carriers of the –511T/T and –31C/C genotypes had a lower prevalence of wasting (p < 0.05), higher body mass index (BMI) (p < 0.05), and higher lean body mass (LBM) (p < 0.01). In a stepwise multiple regression model, age (p < 0.05), BMI (p < 0.01) and the IL-1B –511 genotype (p < 0.01) were independently associated with LBM. The carriers of the +3954T allele had a lower prevalence of inflammation (p < 0.05) and lower serum hsCRP (p < 0.05). The VNTR in IL-1RN was not associated with any markers. Conclusion: The investigated IL-1 gene cluster polymorphisms were associated with nutritional status and inflammation in ESRD patients, but marked differences were found between the genders. These polymorphisms could have prognostic utility for predicting wasting and inflammation in ESRD patients.

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          Most cited references 32

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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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            The role of interleukin-1 in disease.

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              Nutritional assessment: a comparison of clinical judgement and objective measurements.

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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
                2005
                August 2005
                25 August 2005
                : 23
                : 5
                : 384-393
                Affiliations
                aDepartment of Clinical Science, Divisions of Renal Medicine and Baxter Novum and bDepartment of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; cRenal Division Scientific Affairs, Baxter Healthcare Corp., McGaw Park, Ill., USA
                Article
                87196 Blood Purif 2005;23:384–393
                10.1159/000087196
                16088107
                © 2005 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.

                Page count
                Figures: 3, Tables: 6, References: 51, Pages: 10
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/87196
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