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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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      Association between Erythropoietin Responsiveness and Body Composition in Dialysis Patients

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          Abstract

          Background: In contrast to the general population, in maintenance hemodialysis (MHD) patients, small body size is correlated with reduced survival. The reasons for this association are unclear but may be related to a lower uremic toxin load relative to body weight and a higher distribution volume for uremic toxins in large patients. Since anemia is a salient feature in dialysis patients, this study aimed to explore the relationship between body composition and anemia control. Methods: Total adipose tissue (TAT), subcutaneous adipose tissue (SAT) and muscle mass (MM) were estimated by regression models in African-American MHD patients. Patients were grouped for further analysis by gender in tertiles of TAT, SAT, and MM. Analysis of covariance with age and serum albumin as covariates was employed to test for differences in hemoglobin (Hgb, g/dl), erythropoietin use (EPO, U/kg b.w./week), and EPO resistance index (ERI, U/kg b.w./week/Hgb). Results: 479 patients were studied (50.5% females). In both genders, EPO dose and ERI were lower the higher the tertile of TAT and SAT (all p < 0.02). In females, EPO and ERI were inversely related to tertiles of MM (p ≤ 0.001). No difference in Hgb concentration was observed. Conclusion: Anemia control is related to body composition in Black dialysis patients. EPO requirements and EPO resistance are reduced in patients with high TAT, SAT and MM (the latter in females only). A lower uremic load in large dialysis patients may contribute to these findings.

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          Most cited references14

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          Secretory factors from human adipose tissue and their functional role.

          Obesity is characterized by an expanded adipose tissue mass. Recent data suggest that adipose tissue is a multi-functional organ rather than simply a passive storage site for excess energy. It has been clearly demonstrated that human adipose tissue produces a variety of secretory factors that exert multiple effects at both the local and the systemic level. To date, >100 products, covering a broad range of protein families as well as many fatty acids and prostaglandins, have been reported to be secreted by adipose tissue. The source of these secreted factors is not only mature fat cells but also poorly-identified cells present in the stromal-vascular fraction including macrophages. Secreted factors of particular interest include many cytokines or chemokines, such as TNF-alpha, IL-6, IL-8, as well as plasminogen activator inhibitor-1, angiotensin-II, leptin, and adiponectin. In the obese state the expression and secretion of these factors is disturbed. With the exception of adiponectin, most circulating factors are elevated. From this perspective, obesity can be described as a pro-inflammatory condition. In addition, regional differences in adipose expression of many of these factors have been found. There is now growing evidence that many secretory factors play an important role in the pathophysiology of the metabolic and cardiovascular complications of obesity. The question arising from these observations is how the secretory pattern of adipose tissue can be modified by dietary and pharmacological measures to reduce the health risks of obesity.
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            Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients.

            Elements of malnutrition-inflammation complex syndrome (MICS) may blunt the responsiveness of anemia of end-stage renal disease (ESRD) to recombinant human erythropoietin (EPO). The authors examined cross-sectional associations between the required dose of EPO within a 13-week interval as prescribed by practicing nephrologists who were blind to the study and several laboratory values known to be related to nutrition and/or inflammation, as well as the malnutrition-inflammation score (MIS), which is a fully quantitative assessment tool based on the subjective global assessment of nutrition. A total of 339 maintenance hemodialysis (MHD) outpatients, including 181 men, who were aged 54.7 +/- 14.5 years (mean +/- SD), who had undergone dialysis for 36.3 +/- 33.2 months, were selected randomly from 7 DaVita dialysis units in Los Angeles South/East Bay area. The average weekly dose of administered recombinant human EPO within a 13-week interval was 217 +/- 187 U/kg. Patients were receiving intravenous iron supplementation (iron gluconate or dextran) averaging 39.5 +/- 47.5 mg/wk. The MIS and serum concentrations of high-sensitivity C-reactive protein, interleukin 6 (IL-6), tumor necrosis factor-alpha, and lactate dehydrogenase had positive correlation with required EPO dose and EPO responsiveness index (EPO divided by hemoglobin), whereas serum total iron binding capacity (TIBC), prealbumin and total cholesterol, as well as blood lymphocyte count had statistically significant but negative correlations with indices of refractory anemia. Most correlations remained significant even after multivariate adjustment for case-mix and anemia factors and other relevant covariates. Similar associations were noticed across EPO per body weight tertiles via analysis of variance and after estimating odds ratio for higher versus lower tertile via logistic regression after same case-mix adjustment. The existence of elements of MICS as indicated by a high MIS and increased levels of proinflammatory cytokines such as IL-6 as well as decreased nutritional values such as low serum concentrations of total cholesterol, prealbumin, and TIBC correlates with EPO hyporesponsiveness in MHD patients.
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              Removal of P-cresol sulfate by hemodialysis.

              Protein-bound solutes are poorly cleared by dialysis. Among the most extensively studied of these solutes is p-cresol, which has been shown to be toxic in vitro. This study examined the form in which p-cresol circulates and quantified its removal by hemodialysis. HPLC analysis of plasma from hemodialysis patients contained a peak whose mobility corresponded to synthetic p-cresol sulfate (PCS) but no detectable unconjugated p-cresol. Treatment with sulfatase resulted in recovery of this peak as p-cresol, confirming its identity. Subsequent studies compared the removal of PCS and another protein-bound solute, indican, to the removal of urea during clinical hemodialysis treatments. PCS and indican were 94 +/- 1% and 93 +/- 2% bound to plasma protein, respectively. Protein-binding caused a predictable decrease in measured dialytic clearance, which averaged 20 +/- 4 ml/min for PCS and 25 +/- 5 ml/min for indican as compared with 260 +/- 20 ml/min for urea. Volumes of distribution for the protein-bound solutes were greater than the plasma volume, averaging 15 +/- 7 L for PCS and 14 +/- 3 L for indican as compared with 37 +/- 7 for urea. Solute reduction ratios were 20 +/- 9% for PCS, 30 +/- 7% for indican, and 69 +/- 5% for urea. We conclude that p-cresol circulates in the form of its sulfate conjugate, PCS. PCS is poorly removed by hemodialysis because its clearance is limited by protein binding and the ratio of its volume of distribution to its clearance is high.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                978-3-8055-8467-8
                978-3-8055-8468-5
                0253-5068
                1421-9735
                2008
                January 2008
                10 January 2008
                : 26
                : 1
                : 82-89
                Affiliations
                aRenal Research Institute, New York, N.Y., USA; bKrankenhaus der Barmherzigen Brueder, Department of Internal Medicine, Graz, Austria
                Article
                110571 Blood Purif 2008;26:82–89
                10.1159/000110571
                18182803
                8f4a10f6-ea26-4193-bdc7-13369a7748e6
                © 2008 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: 3, Tables: 3, References: 18, Pages: 8
                Categories
                Paper

                Cardiovascular Medicine,Nephrology
                Hemodialysis,Body composition,Anemia,Erythropoietin,Obesity,Reverse epidemiology

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