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      Anemia and iron deficiency among chronic kidney disease Stages 3–5ND patients in the Chronic Kidney Disease Outcomes and Practice Patterns Study: often unmeasured, variably treated

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          Abstract

          Background

          International variation in anemia assessment and management practices in chronic kidney disease (CKD) is poorly understood.

          Methods

          We performed a cross-sectional analysis of anemia laboratory monitoring, prevalence and management in the prospective Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps). A total of 6766 participants with CKD Stages 3a–5ND from nephrology clinics in Brazil, France, Germany and the USA were included.

          Results

          Among patients with anemia (hemoglobin <12 g/dL), 36–58% in Brazil, the USA and Germany had repeat hemoglobin measured and 40–61% had iron indices measured within 3 months of the index hemoglobin measurement. Anemia was more common in the USA and Brazil than in France and Germany across CKD stages. Higher ferritin and lower iron saturation (TSAT) levels were observed with lower hemoglobin levels, and higher ferritin with more advanced CKD. The proportion of anemic patients with ferritin <100 ng/mL or TSAT <20% ranged from 42% in Brazil to 53% in France and Germany, and of these patients, over 40% in Brazil, Germany and the USA, compared with 27% in France, were treated with oral or intravenous iron within 3 months after hemoglobin measurement. The proportion of patients with hemoglobin <10 g/dL treated with erythropoiesis-stimulating agents ranged from 28% in the USA to 57% in Germany.

          Conclusions

          Hemoglobin and iron stores are measured less frequently than per guidelines. Among all regions, there was a substantial proportion of anemic patients with iron deficiency who were not treated with iron, highlighting an area for practice improvement in CKD care.

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          Most cited references46

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          Correction of anemia with epoetin alfa in chronic kidney disease.

          Anemia, a common complication of chronic kidney disease, usually develops as a consequence of erythropoietin deficiency. Recombinant human erythropoietin (epoetin alfa) is indicated for the correction of anemia associated with this condition. However, the optimal level of hemoglobin correction is not defined. In this open-label trial, we studied 1432 patients with chronic kidney disease, 715 of whom were randomly assigned to receive a dose of epoetin alfa targeted to achieve a hemoglobin level of 13.5 g per deciliter and 717 of whom were assigned to receive a dose targeted to achieve a level of 11.3 g per deciliter. The median study duration was 16 months. The primary end point was a composite of death, myocardial infarction, hospitalization for congestive heart failure (without renal replacement therapy), and stroke. A total of 222 composite events occurred: 125 events in the high-hemoglobin group, as compared with 97 events in the low-hemoglobin group (hazard ratio, 1.34; 95% confidence interval, 1.03 to 1.74; P=0.03). There were 65 deaths (29.3%), 101 hospitalizations for congestive heart failure (45.5%), 25 myocardial infarctions (11.3%), and 23 strokes (10.4%). Seven patients (3.2%) were hospitalized for congestive heart failure and myocardial infarction combined, and one patient (0.5%) died after having a stroke. Improvements in the quality of life were similar in the two groups. More patients in the high-hemoglobin group had at least one serious adverse event. The use of a target hemoglobin level of 13.5 g per deciliter (as compared with 11.3 g per deciliter) was associated with increased risk and no incremental improvement in the quality of life. (ClinicalTrials.gov number, NCT00211120 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.
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            A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease.

            Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately tested. In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter. The primary end points were the composite outcomes of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease. Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo (hazard ratio for darbepoetin alfa vs. placebo, 1.05; 95% confidence interval [CI], 0.94 to 1.17; P=0.41). Death or end-stage renal disease occurred in 652 patients assigned to darbepoetin alfa and 618 patients assigned to placebo (hazard ratio, 1.06; 95% CI, 0.95 to 1.19; P=0.29). Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo (hazard ratio, 1.92; 95% CI, 1.38 to 2.68; P<0.001). Red-cell transfusions were administered to 297 patients assigned to darbepoetin alfa and 496 patients assigned to placebo (P<0.001). There was only a modest improvement in patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group. The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event) and was associated with an increased risk of stroke. For many persons involved in clinical decision making, this risk will outweigh the potential benefits. (ClinicalTrials.gov number, NCT00093015.) 2009 Massachusetts Medical Society
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              Normalization of hemoglobin level in patients with chronic kidney disease and anemia.

              Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established. We randomly assigned 603 patients with an estimated glomerular filtration rate (GFR) of 15.0 to 35.0 ml per minute per 1.73 m2 of body-surface area and mild-to-moderate anemia (hemoglobin level, 11.0 to 12.5 g per deciliter) to a target hemoglobin value in the normal range (13.0 to 15.0 g per deciliter, group 1) or the subnormal range (10.5 to 11.5 g per deciliter, group 2). Subcutaneous erythropoietin (epoetin beta) was initiated at randomization (group 1) or only after the hemoglobin level fell below 10.5 g per deciliter (group 2). The primary end point was a composite of eight cardiovascular events; secondary end points included left ventricular mass index, quality-of-life scores, and the progression of chronic kidney disease. During the 3-year study, complete correction of anemia did not affect the likelihood of a first cardiovascular event (58 events in group 1 vs. 47 events in group 2; hazard ratio, 0.78; 95% confidence interval, 0.53 to 1.14; P=0.20). Left ventricular mass index remained stable in both groups. The mean estimated GFR was 24.9 ml per minute in group 1 and 24.2 ml per minute in group 2 at baseline and decreased by 3.6 and 3.1 ml per minute per year, respectively (P=0.40). Dialysis was required in more patients in group 1 than in group 2 (127 vs. 111, P=0.03). General health and physical function improved significantly (P=0.003 and P<0.001, respectively, in group 1, as compared with group 2). There was no significant difference in the combined incidence of adverse events between the two groups, but hypertensive episodes and headaches were more prevalent in group 1. In patients with chronic kidney disease, early complete correction of anemia does not reduce the risk of cardiovascular events. (ClinicalTrials.gov number, NCT00321919 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.
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                Author and article information

                Journal
                Clin Kidney J
                Clin Kidney J
                ckj
                Clinical Kidney Journal
                Oxford University Press
                2048-8505
                2048-8513
                August 2020
                03 August 2019
                03 August 2019
                : 13
                : 4
                : 613-624
                Affiliations
                [1 ] Department of Medicine, University of British Columbia , Vancouver, BC, Canada
                [2 ] Arbor Research Collaborative for Health , Ann Arbor, MI, USA
                [3 ] School of Public Health, University of Michigan , Ann Arbor, MI, USA
                [4 ] Department of Nephrology, University of Michigan , Ann Arbor, MI, USA
                [5 ] School of Medicine, Pontificia Universidade Catolica do Parana , Curitiba, PR, Brazil
                [6 ] Faculdade de Medicina da Bahia School of Medicine, Universidade Federal da Bahia , Salvador, Brazil
                [7 ] Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Science , Niigata, Japan
                [8 ] Nephrological Center, Villingen-Schwenningen , Germany
                [9 ] Department of Internal Medicine, Michigan Medicine, and Department of Epidemiology, School of Public Health, University of Michigan , Ann Arbor MI, USA
                [10 ] CESP, Center for Research in Epidemiology and Population Health, Univ Paris-Saclay, Univ Paris-Sud , UVSQ, Inserm UMRS 1018, Villejuif, France
                [11 ] Division of Nephrology, Ambroise Paré University Hospital , APHP, Boulogne-Billancourt/Paris, France
                Author notes
                Correspondence and offprint requests to: Michelle M. Y. Wong; E-mail: mimywong@ 123456mail.ubc.ca

                See Acknowledgements section for CKDopps Investigators.

                Article
                sfz091
                10.1093/ckj/sfz091
                7467578
                32905241
                eea16315-9d49-4dfc-b1a6-0492c7c8fe0a
                © The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 19 February 2019
                : 21 June 2019
                Page count
                Pages: 12
                Categories
                Original Articles
                AcademicSubjects/MED00340

                Nephrology
                anemia,chronic kidney disease,erythropoiesis-stimulating agents,iron deficiency,iron supplementation

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