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      Variability in hemoglobin levels in hemodialysis patients in the current era: a retrospective cohort study


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          Abstract

          Background: Given regulatory and reimbursement changes in anemia management, we examined hemoglobin variability in a contemporary cohort of maintenance hemodialysis patients. Materials and methods: The study population included > 200,000 hemodialysis patients with Medicare parts A and B as primary payer on October 1, 2012. Based on 25 th and 75 th percentiles, monthly hemoglobin values were categorized as low, intermediate, or high. Six variability categories were created by patterns during the 6-month observation period. Stable categories were: always-low, always-intermediate, always-high; variable patterns were: varying between low and intermediate, intermediate and high, low and high (most-variable). Cox proportional hazard models were used to assess the association between hemoglobin variability and all-cause mortality or major adverse cardiac events (MACE). Results: The 25 th and 75 th hemoglobin percentiles were 10.2 and 11.5 g/dL, respectively, in 2012, vs. 11 and 12.5 g/dL in 2004. ESA doses were lower in all categories in 2012 and transfusion rates higher, particularly for always-low patients. Hemoglobin variability decreased modestly: in 2004, 6.0% were always-intermediate, vs. 9.5% in 2012. In 2012, more patients were always-high and fewer were most-variable. Mortality hazard ratios (HRs) were higher for patients with any low hemoglobin: always-low (HR, 95% CI: 2.07, 1.84 – 2.31), varying between low and intermediate (1.37, 1.29 – 1.45), and most-variable (1.23, 1.16 – 1.31); the pattern was similar for MACE. Conclusions: In 2012 vs. 2004, hemoglobin levels decreased, the range of levels narrowed, and variability decreased modestly; transfusions increased. The highest risk of mortality and MACE appeared to occur in patients with persistently low, rather than highly variable, hemoglobin levels.


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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 Nephrol
                Clin. Nephrol
                Dustri
                Clinical Nephrology
                Dustri-Verlag Dr. Karl Feistle
                0301-0430
                November 2017
                7 September 2017
                : 88
                : 5
                : 254-263
                Affiliations
                [1 ]Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, MN, and
                [2 ]Akebia Therapeutics, Inc., Cambridge, MA, USA
                Author notes
                David T. Gilbertson, PhD, Chronic Disease Research Group, Minneapolis Medical Research Foundation, 701 Park Avenue, Suite S4.100, Minneapolis, MN 55415, USA, dgilbertson@ 123456cdrg.org
                Article
                10.5414/CN109031

                5653974
                28899480
                31ba7011-eea1-4ef4-aa5d-5dba0b7fb3c5
                © Dustri-Verlag Dr. K. Feistle

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 September 2016
                : 11 July 2017
                Categories
                Research Article
                Nephrology

                anemia,hemodialysis,hemoglobin variability,mortality,major adverse cardiac events

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