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      Clinical Value of the Malnutrition-Inflammation-Atherosclerosis Syndrome for Long-Term Prediction of Cardiovascular Mortality in Patients with End-Stage Renal Disease: A 5-Year Prospective Study

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          Abstract

          Background/Aim: Mortality resulting from cardiovascular disease in patients with end-stage renal disease (ESRD) is high. In this study we sought to investigate the clinical value of the malnutrition-inflammation-atherosclerosis (MIA) syndrome for long-term prediction of cardiovascular mortality in patients treated with ESRD. Methods: A total of 42 ESRD patients on hemodialysis were enrolled. Inflammatory markers and nutritional parameters were determined. Carotid atherosclerosis was investigated by ultrasonographically evaluated carotid intima-media thickness (cIMT). Mortality was evaluated at a 5-year follow-up. Results: No correlation was evident between nutritional markers and inflammatory indexes. cIMT was inversely correlated with predialysis serum albumin. In the overall population of 42 patients, 11 (26.2%) died of cardiovascular causes during follow-up. Kaplan-Meier survival curves indicate that cIMT (≧0.9 mm), C-reactive protein (CRP) (>1 mg/dl), and serum albumin (<3.5 g/dl) predict cardiovascular death in patients with ESRD. Conclusions: We have demonstrated that cIMT, CRP and serum albumin predict long-term mortality in ERSD patients. Our study suggests that further investigation of the MIA syndrome will provide insights into the susceptibility to CVD in this patient group.

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          The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis.

          W Owen, N L Lew, Y. Liu … (1993)
          Among patients with end-stage renal disease who are treated with hemodialysis, solute clearance during dialysis and nutritional adequacy are determinants of mortality. We determined the effects of reductions in blood urea nitrogen concentrations during dialysis and changes in serum albumin concentrations, as an indicator of nutritional status, on mortality in a large group of patients treated with hemodialysis. We analyzed retrospectively the demographic characteristics, mortality rate, duration of hemodialysis, serum albumin concentration, and urea reduction ratio (defined as the percent reduction in blood urea nitrogen concentration during a single dialysis treatment) in 13,473 patients treated from October 1, 1990, through March 31, 1991. The risk of death was determined as a function of the urea reduction ratio and serum albumin concentration. As compared with patients with urea reduction ratios of 65 to 69 percent, patients with values below 60 percent had a higher risk of death during follow-up (odds ratio, 1.28 for urea reduction ratios of 55 to 59 percent and 1.39 for ratios below 55 percent). Fifty-five percent of the patients had urea reduction ratios below 60 percent. The duration of dialysis was not predictive of mortality. The serum albumin concentration was a more powerful (21 times greater) predictor of death than the urea reduction ratio, and 60 percent of the patients had serum albumin concentrations predictive of an increased risk of death (values below 4.0 g per deciliter). The odds ratio for death was 1.48 for serum albumin concentrations of 3.5 to 3.9 g per deciliter and 3.13 for concentrations of 3.0 to 3.4 g per deciliter. Diabetic patients had lower serum albumin concentrations and urea reduction ratios than nondiabetic patients. Low urea reduction ratios during dialysis are associated with increased odds ratios for death. These risks are worsened by inadequate nutrition.
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            Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome).

            P Stenvinkel, O Heimbürger, B. Lindholm … (2000)
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              Immunologic function and survival in hemodialysis patients.

              Paul L Kimmel, Terry Phillips, Samuel J Simmens … (1998)
              Although the medical determinants of mortality in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) are well appreciated, the contribution of immunologic parameters to survival in such patients is unclear, especially when variations in age, medical comorbidity and nutrition are controlled. In addition, although dysregulation of cytokine metabolism has been appreciated in patients with ESRD, the association of these parameters with outcomes has not been established. Recently, the type of dialyzer used in patients' treatment has been associated with survival, but the mechanisms underlying these findings, including their immune effects, have not been established. We conducted a prospective, cross-sectional, observational multicenter study of urban HD patients to determine the contribution of immunological factors to patient survival. We hypothesized increased proinflammatory cytokines would be associated with increased mortality, and that improved immune function would be associated with survival. Patients were assessed using demographic and anthropometric indices, Kt/V, protein catabolic rate (PCR) and immunologic variables including circulating cytokine [interleukin (IL)-1, IL-2, IL-4, IL-5, IL-6, IL-12, IL-13 and tumor necrosis factor (TNF)-alpha] levels, total hemolytic complement activity (CH50), and T cell number and function. A severity index, previously demonstrated to be a mortality marker, was used to grade medical comorbidity. A Cox proportional hazards model, controlling for patients' age, severity index, level of serum albumin concentration, dialyzer type and dialysis site was used to asses relative survival risk. Two hundred and thirty patients entered the study. The mean (+/- SD) age of the population was 54.4 +/- 14.2 years, mean serum albumin concentration was 3.86 +/- 0.47 g/dl, mean PCR was 1.1 +/- 0.28 g/kg/day, and mean Kt/V 1.2 +/- 0.3. Patients' serum albumin concentration was correlated with levels of Kt/V and PCR, and their circulating IL-13 and TNF-alpha levels, but negatively with their circulating IL-2 levels, T-cell number and T-cell antigen recall function. T-cell antigen recall function correlated negatively with PCR, but not Kt/V. There was no correlation of any other immune parameter and medical or demographic factor. Immune parameters, were all highly intercorrelated. Mean level of circulating cytokines in HD patients were in all cases greater than those of a normal control group. There were few differences in medical risk factors or immune parameters between patients treated with different types of dialyzers. After an almost three-year mean follow-up period, increased IL-1, TNF-alpha, IL-6, and IL-13 levels were significantly associated with increased relative mortality risk, while higher levels of IL-2, IL-4, IL-5, IL-12, T-cell number and function, and CH50 were associated with improved survival. The difference in survival between patients treated with unmodified cellulose dialyzers and modified or synthetic dialyzers approached the level of statistical significance, but there were no differences in levels of circulating cytokines between these two groups. Higher levels of circulating proinflammatory cytokines are associated with mortality, while immune parameters reflecting improved T-cell function are associated with survival in ESRD patients treated with HD, independent of other medical risk factors. These factors may serve as markers for outcome. The mechanism underlying the relationship of immune function and survival, and the effect of interventions to normalize immune function in HD patients should be studied.
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                Author and article information

                Journal
                Journal ID (publisher-id): NEC
                Journal ID (nlm-ta): Nephron Clin Pract
                Journal ID (doi): 10.1159/issn.1660-2110
                Title: Nephron Clinical Practice
                Publisher: S. Karger AG
                ISSN (Electronic): 1660-2110
                Publication date Subscription-year: 2008
                Publication date (Print): March 2008
                Publication date (Electronic): 22 January 2008
                Volume: 108
                Issue: 2
                Pages: c99-c105
                Affiliations
                Departments of aNephrology and Rheumatology, bInternal Medicine, cRadiology, and dBiostatistics, Uludag University Medical School, Bursa, Turkey
                Article
                Publisher ID: 113526 Other ID: Nephron Clin Pract 2008;108:c99
                DOI: 10.1159/000113526
                PubMed ID: 18212491
                SO-VID: aeaef01b-78ea-4127-928b-ed604677791c
                Copyright © © 2008 S. Karger AG, Basel
                License:

                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
                Date received : 18 June 2007
                Date accepted : 30 August 2007
                Page count
                Figures: 2, Tables: 3, References: 21, Pages: 1
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: End-stage renal disease,Hemodialysis,Cardiovascular disease,Inflammation,Malnutrition,Mortality
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: End-stage renal disease, Hemodialysis, Cardiovascular disease, Inflammation, Malnutrition, Mortality

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