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      Dosing of Erythropoiesis-Stimulating Agents Can Be Reduced by a New Administration Regimen

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          Abstract

          Background/Aims:At our hemodialysis (HD) unit, we noted a drop in the treatment dose of erythropoietin-stimulating agents (ESAs) when the frequency of dose adjustment was reduced from weekly, where doses were withheld if hemoglobin was >130 g/l, to monthly, where doses were not withheld. The aim of this study was to find an explanation for this reduction in ESA requirement. Methods: This is a retrospective study on 18 stable HD patients. Comparable follow-up periods of 6 months with the two different ESA adjustment regimens were established and data on ESA dose, hemoglobin and known predictors of ESA response were collected. Results: With the new ESA administration regimen, a 22.5% drop in the total ESA dose was noted. The corresponding fall in the erythropoietin resistance index was 20.0%. Simultaneously, the dialysis dose and transferrin saturation increased significantly. However, in a multivariate linear regression model, changes in these factors did not significantly predict changes in ESA requirement. No relevant changes were noted in other erythropoiesis-modulating factors. Conclusion: Frequent dose adjustments and the current ESA administration practice of withholding ESA doses does not seem to reduce ESA demand. On the contrary, such practice is likely to increase ESA requirement over time.

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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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            KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target.

            (2007)
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              Factors predicting malnutrition in hemodialysis patients: a cross-sectional study.

              Signs of protein-energy malnutrition are common in maintenance hemodialysis (HD) patients and are associated with increased morbidity and mortality. To evaluate the nutritional status and relationship between various parameters used for assessing malnutrition, we performed a cross-sectional study in 128 unselected patients treated with hemodialysis (HD) thrice weekly for at least two weeks. Global nutritional status was evaluated by the subjective global nutritional assessment (SGNA). Body weight, skinfold thicknesses converted into % body fat mass (BFM), mid-arm muscle circumference, hand-grip strength and several laboratory values, including serum albumin (SA1b), plasma insulin-like growth factor I (p-IGF-I), serum C-reactive protein (SCRP) and plasma free amino acids, were recorded. Dose of dialysis and protein equivalence of nitrogen appearance (nPNA) were evaluated by urea kinetic modeling. The patients were subdivided into three groups based on SGNA: group I, normal nutritional status (36%); group II, mild malnutrition (51%); and group III, moderate or (in 2 cases) severe malnutrition (13%). Clinical factors associated with malnutrition were: high age, presence of cardiovascular disease and diabetes mellitus. nPNA and Kt/V(urea) were similar in the three groups. However, when normalized to desirable body wt, both were lower in groups II and III than in group I. Anthropometric factors associated with malnutrition were low body wt, skinfold thickness, mid-arm muscle circumference (MAMC), and handgrip strength. Biochemical factors associated with malnutrition were low serum levels of albumin and creatinine and low plasma levels of insulin-like growth factor 1 (IGF-1) and branched-chain amino acids (isoleucine, leucine and valine). The serum albumin (SAlb) level was not only a predictor of nutritional status, but was independently influenced by age, sex and SCRP. Plasma IGF-1 levels also reflected the presence and severity of malnutrition and appeared to be more closely associated than SAlb with anthropometric and biochemical indices of somatic protein mass. Elevated SCRP (> 20 mg/liter), which mainly reflected the presence of infection/inflammation and was associated with hypoalbuminemia, was more common in malnourished patients than in patients with normal nutritional status, and also more common in elderly than in younger patients. Plasma amino acid levels, with the possible exception of the branched-chain amino acids (isoleucine, leucine, valine), seem to be poor predictors of nutritional status in hemodialysis patients.
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                Author and article information

                Journal
                NNE
                NNE
                10.1159/issn.1664-5529
                Nephron Extra
                S. Karger AG
                1664-5529
                2011
                July – December 2011
                19 August 2011
                : 1
                : 1
                : 45-54
                Affiliations
                Department of Molecular and Clinical Medicine-Nephrology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
                Author notes
                *Bergur V. Stefánsson, MD, Department of Nephrology, Sahlgrenska University Hospital, SE–413 45 Gothenburg (Sweden), Tel. +46 31 342 10 00, E-Mail bergur.stefansson@wlab.gu.se
                Article
                329889 PMC3290861 Nephron Extra 2011;1:45–54
                10.1159/000329889
                PMC3290861
                22470378
                3c12aa0e-5077-4a0c-8614-6ec767d55599
                © 2011 S. Karger AG, Basel

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. 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
                : 01 June 2011
                Page count
                Figures: 2, Tables: 5, Pages: 10
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Anemia,Chronic renal failure,Renal anemia,Erythropoietin-stimulating agents,Hemodialysis,Erythropoietin responsiveness

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