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      Intravenous Iron Sucrose in Chinese Hemodialysis Patients with Renal Anemia

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      ,
      Blood Purification
      S. Karger AG
      Erythropoietin, Hemodialysis, Renal anemia, Iron sucrose

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          Abstract

          Background/Aims: Renal anemia is one of the commonest complications of chronic renal failure. Iron deficiency is the most common factor which affects the efficacy of recombinant human erythropoietin (EPO) therapy. Intravenous (i.v.) iron preparations are commonly used in Western countries, but iron sucrose is seldom used in Chinese patients on maintenance hemodialysis. The aim of the present study was to explore the safety and efficacy of i.v. iron sucrose in Chinese patients on maintenance hemodialysis and to explore the optimal administration frequency. Methods: One hundred and thirty-six patients on maintenance hemodialysis were involved in this randomized, controlled, parallel-group, single-center trial. Seventy patients received i.v. iron sucrose (Venofer®, delivering 100 mg iron) twice a week for 8 weeks, then once a week for another 4 weeks. The other 66 patients received oral (p.o.) ferrous succinate 200 mg t.i.d. for 12 weeks. Levels of serum ferritin (SF), transferrin saturation (TSAT), hemoglobin (Hb) and hematocrit (Hct) were assessed at baseline and then again after 4, 8 and 12 weeks of treatment. Results: There were no differences between i.v. and p.o. groups in terms of sex, age, duration of hemodialysis, dialysis frequency per week, EPO dosage per week, the level of intact parathyroid hormone, serum creatinine, blood urea nitrogen, or hematological parameters at baseline. After 8 and 12 weeks of treatment, mean Hb concentration and Hct were significantly increased in the i.v. group, and were also significantly higher than those in the p.o. group. Levels of SF and TSAT were also significantly increased in the i.v. group, and significantly higher than in the p.o. group. After 8 weeks, the response rate in the i.v. group was 88.6%, which was significantly higher than that in the p.o. group. The mean EPO dose was significantly lower in the i.v. group than the p.o. group. Hb, Hct, SF and TSAT levels were maintained between 8 and 12 weeks in the i.v. group despite the decrease in dose frequency. There were no adverse events related to i.v. iron administration. Twenty-two patients in the p.o. group had adverse gastrointestinal effects. After 12 weeks, the cost of EPO + i.v. iron was significantly higher than the cost of EPO + p.o. iron. Conclusion: Intravenous iron sucrose can effectively increase serum iron parameters and Hb levels in Chinese patients on maintenance hemodialysis and is well tolerated. Infusion of i.v. iron sucrose 100 mg per week can maintain serum iron parameters and Hb levels in Chinese patients on maintenance hemodialysis and can permit reductions in the required dose of EPO. However, the total cost of i.v. iron is relatively high.

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          Most cited references10

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          Anemia, chronic renal disease and congestive heart failure--the cardio renal anemia syndrome: the need for cooperation between cardiologists and nephrologists.

          Many patients with congestive heart failure (CHF) fail to respond to maximal CHF therapy and progress to end stage CHF with many hospitalizations, poor quality of life (QoL), progressive chronic kidney disease (CKD) which can lead to end stage kidney disease (ESKD), or die of cardiovascular complications within a short time. One factor that has generally been ignored in many of these people is the fact that they are often anemic. The anemia in CHF is due mainly to the frequently-associated CKD but also to the inhibitory effects of cytokines on erythropoietin production and on bone marrow activity, as well as to their interference with iron absorption from the gut and their inhibiting effect on the release of iron from iron stores. Anemia itself may further worsen cardiac and renal function and make the patients resistant to standard CHF therapy. Indeed anemia in CHF has been associated with increased severity of CHF, increased hospitalization, worse cardiac function and functional class, the need for higher doses of diuretics, progressive worsening of renal function and reduced QoL. In both controlled and uncontrolled studies of CHF, the correction of the anemia with erythropoietin (EPO) and oral or intravenous (IV) iron has been associated with improvement in many cardiac and renal parameters and an increased QoL. EPO itself may also play a direct role in improving the heart unrelated to the improvement of the anemia--by reducing apoptosis of cardiac and endothelial cells, increasing the number of endothelial progenitor cells, and improving endothelial cell function and neovascularization of the heart. Anemia may also play a role in the worsening of acute myocardial infarction and chronic coronary heart disease (CHD) and in the cardiovascular complications of renal transplantation. Anemia, CHF and CKD interact as a vicious circle so as to cause or worsen each other- the so-called cardio renal anemia syndrome. Only adequate treatment of all three conditions can prevent the CHF and CKD from progressing.
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            Sodium ferric gluconate complex in hemodialysis patients: adverse reactions compared to placebo and iron dextran.

            Parenteral iron is often required by hemodialysis patients to maintain adequate iron stores. Until recently, the only available form of intravenous iron was iron dextran, which is associated with significant adverse reactions, including anaphylaxis and death. Sodium ferric gluconate complex (SFGC) was recently approved for use in the U.S. under FDA's priority drug review. This Phase IV study was designed to evaluate the safety of a single dose of intravenous SFGC as compared to placebo and a historical iron dextran control. This multicenter, crossover, randomized, double blind, placebo-controlled prospective comparative study was performed in hemodialysis patients requiring at least 125 mg of elemental iron. The historical control was obtained from a meta-analysis of four publications examining outcomes in patients exposed to iron dextran. SFGC naïve patients were administered SFGC without a test dose, undiluted, at a rate of 125 mg over 10 minutes, and compared to placebo comprising bacteriostatic saline. A total of 2534 patients were enrolled. The incidence of drug intolerance (an adverse event precluding re-exposure) was significantly less [0.44%, confidence interval (CI) 0.21 to 0.71%] after SFGC as compared to the iron dextran control (2.47%, CI 1.87 to 3.07%, P < 0.0001), but higher than after placebo (0.1%, P = 0.02). There was no difference found between SFGC and placebo in serious adverse events. A single life-threatening event occurred after SFGC (0.04%, CI 0.00 to 0.22%), which was significantly less than following iron dextran (0.61%, CI 0.36 to 0.86%), P = 0.0001. SFGC is well tolerated when given by intravenous push without a test dose. SFGC has a significantly lower incidence of drug intolerance and life-threatening events as compared to previous studies using iron dextran. The routine use of iron dextran in hemodialysis patients should be discontinued.
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              Efficacy and safety of iron sucrose for iron deficiency in patients with dialysis-associated anemia: North American clinical trial.

              Iron sucrose has been used to provide intravenous (IV) iron therapy to patients outside the United States for more than 50 years. In a multicenter North American clinical trial, we determined the efficacy and safety of iron sucrose therapy in patients with dialysis-associated anemia, evidence of iron deficiency, and below-target hemoglobin (Hgb) levels despite epoetin therapy. Evidence of iron deficiency included a transferrin saturation (Tsat) less than 20% and ferritin level less than 300 ng/mL, and below-target Hgb levels included values less than 11.0 g/dL. We administered iron sucrose in 10 doses, each administered undiluted as 100 mg IV push over 5 minutes, without a prior test dose. We assessed efficacy by determining the subsequent change in Hgb, Tsat, and ferritin values. We assessed safety by recording blood pressure and adverse events after iron sucrose injection and comparing results with those for the same patients during an observation control period. Results showed a significant increase in Hgb level that was first evident after three doses of iron sucrose and persisted at least 5 weeks after the 10th dose. Tsat and ferritin levels also increased significantly and remained elevated. In 77 enrolled patients, including those with previous iron dextran sensitivity, other drug allergies, or concurrent angiotensin-converting enzyme inhibitor use, we saw no serious adverse drug reactions and no change in intradialytic blood pressure associated with iron sucrose administration. We conclude that iron sucrose injection administered as 1,000 mg in 10 divided doses by IV push without a prior test dose is safe and effective for the treatment of iron deficiency in patients with dialysis-associated anemia.
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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
                2008
                March 2008
                22 January 2008
                : 26
                : 2
                : 151-156
                Affiliations
                Blood Purification Center, Beijing Chaoyang Hospital, Capital University of Medical Sciences, Beijing, China
                Article
                113529 Blood Purif 2008;26:151–156
                10.1159/000113529
                18212498
                7070c977-0fd4-4f7a-a485-1e1b72ebcd13
                © 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
                : 06 June 2007
                : 09 November 2007
                Page count
                Tables: 5, References: 21, Pages: 6
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Renal anemia,Erythropoietin,Hemodialysis,Iron sucrose
                Cardiovascular Medicine, Nephrology
                Renal anemia, Erythropoietin, Hemodialysis, Iron sucrose

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