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      Erythropoietin Resistance Index and the All-Cause Mortality of Chronic Hemodialysis Patients

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          Abstract

          Background: Evidence suggests hemodialysis (HD) patients with resistance to erythropoiesis-stimulating agents (ESA) have a higher mortality rate. We investigated the association between ESA responsiveness and mortality in our HD population. Methods: A prospective cohort study of chronic HD patients was conducted at Jyoban Hospital in Fukushima, Japan. We collected data on patient demographic factors, comorbidities, dialysis vintage, body weight, ESA dose and hemoglobin concentration, as well as data on known risk factors for ESA hyporesponsiveness. The erythropoietin resistance index (ERI) was calculated by dividing the weekly body-weight-adjusted epoetin dose by the hemoglobin concentration. The association between ESA hyporesponsiveness estimated by the highest tertile of ERI and mortality was investigated by using the Cox proportional hazards model with adjustments for demographic factors, comorbidities, dialysis adequacy and serum biochemical data. Results: A total of 248 patients were included as subjects in the cohort, and their overall 2-year mortality rate was 13.3%. According to the results of the Kaplan-Meier analysis, patients with an ERI in the highest tertile had significantly higher mortality than patients with an ERI in the lower two tertiles (p = 0.0121). The highest ERI tertile was associated with higher all-cause mortality in both the unadjusted hazards model (hazard ratio, HR: 4.429; 95% CI: 1.249-15.704) and the adjusted hazards model (HR: 4.204; 95% CI: 1.173-15.065). Conclusions: A higher degree of resistance to ESA in chronic HD patients is associated with increased mortality.

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          Most cited references23

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          Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences.

          Protein-energy malnutrition (PEM) and inflammation are common and usually concurrent in maintenance dialysis patients. Many factors that appear to lead to these 2 conditions overlap, as do assessment tools and such criteria for detecting them as hypoalbuminemia. Both these conditions are related to poor dialysis outcome. Low appetite and a hypercatabolic state are among common features. PEM in dialysis patients has been suggested to be secondary to inflammation; however, the evidence is not conclusive, and an equicausal status or even opposite causal direction is possible. Hence, malnutrition-inflammation complex syndrome (MICS) is an appropriate term. Possible causes of MICS include comorbid illnesses, oxidative and carbonyl stress, nutrient loss through dialysis, anorexia and low nutrient intake, uremic toxins, decreased clearance of inflammatory cytokines, volume overload, and dialysis-related factors. MICS is believed to be the main cause of erythropoietin hyporesponsiveness, high rate of cardiovascular atherosclerotic disease, decreased quality of life, and increased mortality and hospitalization in dialysis patients. Because MICS leads to a low body mass index, hypocholesterolemia, hypocreatininemia, and hypohomocysteinemia, a "reverse epidemiology" of cardiovascular risks can occur in dialysis patients. Therefore, obesity, hypercholesterolemia, and increased blood levels of creatinine and homocysteine appear to be protective and paradoxically associated with a better outcome. There is no consensus about how to determine the degree of severity of MICS or how to manage it. Several diagnostic tools and treatment modalities are discussed. Successful management of MICS may ameliorate the cardiovascular epidemic and poor outcome in dialysis patients. Clinical trials focusing on MICS and its possible causes and consequences are urgently required to improve poor clinical outcome in dialysis patients.
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            KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease.

            , (2006)
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              Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial.

              We administered recombinant human erythropoietin to 25 anemic patients with end-stage renal disease who were undergoing hemodialysis. The recombinant human erythropoietin was given intravenously three times weekly after dialysis, and transfusion requirements, hematocrit, ferrokinetics, and reticulocyte responses were monitored. Over a range of doses between 15 and 500 units per kilogram of body weight, dose-dependent increases in effective erythropoiesis were noted. At 500 units per kilogram, changes in the hematocrit of as much as 10 percentage points were seen within three weeks, and increases in ferrokinetics of three to four times basal values, as measured by erythron transferrin uptake, were observed. Of 18 patients receiving effective doses of recombinant human erythropoietin, 12 who had required transfusions no longer needed them, and in 11 the hematocrit increased to 35 percent or more. Along with the rise in hematocrit, four patients had an increase in blood pressure, and a majority had increases in serum creatinine and potassium levels. No organ dysfunction or other toxic effects were observed, and no antibodies to the recombinant hormone were formed. These results demonstrate that recombinant human erythropoietin is effective, can eliminate the need for transfusions with their risks of immunologic sensitization, infection, and iron overload, and can restore the hematocrit to normal in many patients with the anemia of end-stage renal disease.
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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
                2014
                May 2014
                05 March 2014
                : 37
                : 2
                : 106-112
                Affiliations
                aDepartment of Medicine, Jyoban Hospital, Fukushima, and bDepartment of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan
                Author notes
                *Kosaku Nitta, Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan), E-Mail knitta@kc.twmu.ac.jp
                Article
                358215 Blood Purif 2014;37:106-112
                10.1159/000358215
                24603656
                b0bfece7-c1fe-4976-b5b1-d0c9fc441fe2
                © 2014 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
                : 02 October 2013
                : 22 December 2013
                Page count
                Figures: 4, Tables: 3, Pages: 7
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Erythropoietin,Anemia,End-stage renal disease,Mortality ,Hyporesponsiveness,Epoetin

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