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      Evaluating the effectiveness of IV iron dosing for anemia management in common clinical practice: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS)

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          Abstract

          Background

          Anemia management protocols in hemodialysis (HD) units differ conspicuously regarding optimal intravenous (IV) iron dosing; consequently, patients receive markedly different cumulative exposures to IV iron and erythropoiesis-stimulating agents (ESAs). Complementary to IV iron safety studies, our goal was to gain insight into optimal IV iron dosing by estimating the effects of IV iron doses on Hgb, TSAT, ferritin, and ESA dose in common clinical practice.

          Methods

          9,471 HD patients (11 countries, 2009-2011) in the DOPPS, a prospective cohort study, were analyzed. Associations of IV iron dose (3-month average, categorized as 0, <300, ≥300 mg/month) with 3-month change in Hgb, TSAT, ferritin, and ESA dose were evaluated using adjusted GEE models.

          Results

          Relative change : Monotonically positive associations between IV iron dose and Hgb, TSAT, and ferritin change, and inverse associations with ESA dose change, were observed across multiple strata of prior Hgb, TSAT, and ferritin levels. Absolute change : TSAT, ferritin, and ESA dose changes were nearest zero with IV iron <300 mg/month, rather than 0 mg/month or ≥300 mg/month by maintenance or replacement dosing. Findings were robust to numerous sensitivity analyses.

          Conclusions

          Though residual confounding cannot be ruled out in this observational study, findings suggest that IV iron dosing <300 mg/month, as commonly seen with maintenance dosing of 100-200 mg/month, may be a more effective approach to support Hgb than the higher IV iron doses (300-400 mg/month) often given in many European and North American hemodialysis clinics. Alongside studies supporting the safety of IV iron in 100-200 mg/month dose range, these findings help guide the rational dosing of IV iron in anemia management protocols for everyday hemodialysis practice.

          Electronic supplementary material

          The online version of this article (10.1186/s12882-017-0745-9) contains supplementary material, which is available to authorized users.

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          Most cited references41

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          Kidney Disease: Improving Global Outcomes guidelines on anaemia management in chronic kidney disease: a European Renal Best Practice position statement.

          Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group has produced comprehensive clinical practice guidelines for the management of anaemia in CKD patients. These guidelines addressed all of the important points related to anaemia management in CKD patients, including therapy with erythropoieis stimulating agents (ESA), iron therapy, ESA resistance and blood transfusion use. Because most guidelines were 'soft' rather than 'strong', and because global guidelines need to be adapted and implemented into the regional context where they are used, on behalf of the European Renal Best Practice Advisory Board some of its members, and other external experts in this field, who were not participants in the KDIGO guidelines group, were invited to participate in this anaemia working group to examine and comment on the KDIGO documents in this position paper. In this article, the group concentrated only on those guidelines which we considered worth amending or adapting. All guidelines not specifically mentioned are fully endorsed.
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            The Dialysis Outcomes and Practice Patterns Study (DOPPS): design, data elements, and methodology.

            The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective, observational study designed to elucidate aspects of hemodialysis practice that are associated with the best outcomes for hemodialysis patients. In DOPPS I, 308 hemodialysis units from 7 countries participated, including 145 facilities from the United States (1996-2001), 62 facilities from Japan (1999-2001), and 101 facilities from France, Germany, Italy, Spain, and the United Kingdom (all 1998-2000). DOPPS II (2002-2004) has included 320 hemodialysis units and more than 12,400 hemodialysis patients from the 7 DOPPS I countries as well as Australia, Belgium, Canada, New Zealand, and Sweden. Dialysis units are chosen via a stratified random selection procedure to provide proportional sampling by region and type of facility within each country. In DOPPS I and II, longitudinal data have been collected from both a prevalent (cross-sectional) patient sample and an incident patient sample. Data have also been collected on numerous facility practice patterns. Most DOPPS analyses incorporate both facility- and patient-level data in regression-based analyses to investigate predictors of survival, hospitalization, quality of life, vascular access type, and other outcomes. DOPPS longitudinal data also help identify trends in subject characteristics, practice indicators, medication use, and outcomes. The DOPPS remains a unique source of data on hemodialysis patients and facilities. It continues to refine its methods of data collection and analysis with the goal of improving hemodialysis practice and end-stage renal disease patient lives worldwide.
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              Iron management in chronic kidney disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference.

              Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.
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                Author and article information

                Contributors
                (734)665-4108 , bruce.robinson@arborresearch.org
                maria.larkina@arborresearch.org
                brian.bieber@arborresearch.org
                Werner.Kleophas@davita-dialyse.de
                yunlisph@umich.edu
                f.locatelli@ospedale.lecco.it
                keith.mccullough@arborresearch.org
                jackiegnolen@gmail.com
                friedrich.port@arborresearch.org
                ronald.pisoni@arborresearch.org
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                9 November 2017
                9 November 2017
                2017
                : 18
                : 330
                Affiliations
                [1 ]ISNI 0000 0004 0628 9837, GRID grid.413857.c, Arbor Research Collaborative for Health, ; 340 E. Huron, Suite 300, Ann Arbor, MI 48104 USA
                [2 ]ISNI 0000000086837370, GRID grid.214458.e, University of Michigan, ; 1415 Washington Heights, Ann Arbor, MI 48109 USA
                [3 ]Dialysezentrum Karlstrasse, Karlstraße 17-19, 40210 Düsseldorf, Germany
                [4 ]ISNI 0000 0004 0493 6789, GRID grid.413175.5, Department of Nephrology, , Alessandro Manzoni Hospital, ; Via dell’Eremo, 9/11, 23900 Lecco, LC Italy
                [5 ]ISNI 0000 0004 0422 3332, GRID grid.467607.4, Vifor Pharma, ; Flughofstrasse 61, 8152 Glattbrugg, Switzerland
                Article
                745
                10.1186/s12882-017-0745-9
                5679150
                29121874
                eef7e3cb-fc3c-45ef-90fa-6458ed8d300f
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 24 February 2017
                : 20 October 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100002429, Amgen;
                Funded by: FundRef http://dx.doi.org/10.13039/501100004095, Kyowa Hakko Kirin;
                Funded by: FundRef http://dx.doi.org/10.13039/100004339, Sanofi;
                Funded by: FundRef http://dx.doi.org/10.13039/100007658, Baxter Healthcare Corporation;
                Funded by: FundRef http://dx.doi.org/10.13039/501100006484, Vifor Pharma;
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Nephrology
                anemia,ferritin,hemodialysis,hemoglobin,iv iron,tsat
                Nephrology
                anemia, ferritin, hemodialysis, hemoglobin, iv iron, tsat

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