Intravenous Iron Dose Research Articles

Impact of a Patient Blood Management Program and an Outpatient Anemia Management Protocol on Red Cell Transfusions in Oncology Inpatients and Outpatients.

Patient blood management (PBM) programs are associated with reduced transfusion usage, reduced hospital costs, and improved patient outcomes. The application of PBM principles in patients with malignant disease might achieve similar results. However, this population presents unique challenges. The aim of the present study was to investigate the impact of a PBM program on blood usage and patient outcomes in cancer patients, particularly in the setting of restricted use of erythropoiesis-stimulating agents (ESAs). A retrospective observational study was performed of patients admitted with a primary diagnosis of malignancy treated at Eastern Maine Medical Center as inpatients or outpatients, or both, from January 2008 through July 2013. The proportion of inpatients and outpatients receiving ESAs decreased from 2.9% in 2008 to 1.1% in 2013 (p < .001). During the same period, an increase occurred in the mean dose of intravenous (IV) iron from 447 mg (95% confidence interval [CI], 337-556) to 588 mg (95% CI, 458-718). The mean red blood cell (RBC) units transfused per inpatient and outpatient episode decreased from 0.067 to 0.038 unit (p < .001). In inpatients, significant increases occurred in the proportion of single-unit RBC transfusions (p < .001) and patients infused with IV iron (p = .02), and significant decreases in the mean pretransfusion hemoglobin (p = .02) and RBC transfusion rate (p = .04). In-hospital mortality and length of stay did not change significantly during this period. Despite the decreased use of ESA therapy, the implementation of a PBM program and outpatient anemia management protocol in cancer patients at our medical center was associated with significant reductions in RBC usage.

Very low doses of direct intravenous iron in each session as maintenance therapy in haemodialysis patients

Background: Intravenous (IV) iron supplementation is widely used in haemodialysis (HD) patients to treat their periodic losses. However, the ideal doses and frequency is unknown. We analyse whether treatment with 20 mg of iron IV at the end of each session of HD affects erythropoiesis activity (EA) and functional iron (FI). Methods: In 36 patients, we measure the reticulocyte count and the content of haemoglobin reticulocyte (CHr) as EA and FI markers respectively, before and four weeks after the end of treatment. Before the study, 23 patients received another different therapy with IV iron as maintenance therapy. Results: Reticulocyte count was 49.7±23, 8 x103 before and 47.2±17, 2 x103 after the treatment (P=0.51). The CHr was 34.82±3,7 pg and 34.44±3.51 pg respectively (P=0.35), showing an excellent correlation with the others FI markers (serum iron r=0,6 p=0,001; saturation transferrin r=0,49 p=0,004); that is not seen with the serum ferritin (r=0.23 p=0.192) or the hepcidin (r=0.22 p=0.251). The thirteen patients who did not receive the iron prior the study, showed a high FI levels but not an increase of the serum ferritin or the serum hepcidin. Conclusions: The administration of a little quantity of iron at the end of every HD session keeps the EA and the FI and allows reducing the iron overload administrated and/or decreasing the iron stores markers in some patients.

HemobloginA2 Levels Associate with Lower ESA-Dose in African-Americans with Sickle Cell Trait and End-Stage Kidney Disease

Introduction: We have previously demonstrated that African-Americans with end-stage kidney disease on hemodialysis receive higher doses of erythropoietin-stimulating agents (ESA) if they also have sickle cell trait (SCT). In sickle cell disease, the severity of clinical manifestations is modified by the quantity of hemoglobin S (HbS) expressed and attenuated by hemoglobin F (HbF) expression. Measures of hemoglobin A2 (HbA2) are reported to be higher in SCT although this may be related to testing artifact. We evaluated if ESA dosing in SCT patients on hemodialysis is associated with differences in the amount of these hemoglobins.Methods: From a cohort of 155 African-Americans on hemodialysis, we collected data on the level of hemoglobin type (HbA, HbS, HbA2, HbF) determined by cation-exchange high-pressure liquid chromatography (HPLC) studies. Only SCT individuals were included. Demographics and medical history were reviewed for covariates including age, sex, BMI, diabetes mellitus, history of gastrointestinal bleeding, vascular access type, time on dialysis and missed treatments. All laboratory studies were reviewed and averaged from a 3-month period for ferritin, iron saturation, parathyroid hormone, serum albumin, serum phosphorus, and adequacy studies (Kt/V). We calculated delivered ESA doses and intravenous iron doses as per-treatment dosing. We compared continuous measures of the amount of each hemoglobin type with ESA dose using SpearmanÕs correlation. We also constructed multivariable linear regression models using backward elimination to identify relevant confounders from a full model. Iron dosing and iron percent saturation were retained a priori.Results: 24(15%) of the 155 patients had SCT. Of the individuals excluded, 9 had hemoglobin C trait and 1 had β-thalassemia trait and the rest had normal hemoglobin variants. Median age of the 24 subjects was 62.1 years (IQR 48.7, 69.2) and 13 were male (54.2%). None had measurable HbF. Other relevant clinical and demographic data are presented in Table 1. In unadjusted analyses, percent of HbS weakly correlated with average ESA dose but was not statistically significant (ρ= -0.27, 95% -0.61, 0.15; p=0.2). HbA2 however had a relatively strong negative correlation with ESA dose that was statistically significant (ρ= -0.44, 95% CI -0.72, -0.05; p=0.03). After adjusting for age, time on dialysis, iron dose, iron percent saturation, albumin and parathyroid hormone, HbA2 still demonstrated a statistically significant negative correlation with ESA dose (p=0.04). For each tenth of percent increase in HbA2, ESA dose was lower by approximately 440 U.Conclusions: African-American hemodialysis patients with SCT receive higher doses of ESA to achieve similar hemoglobin levels as other patients. Among these individuals, higher HbA2 levels are associated with lower ESA dose even after adjustment for confounders. Although measures of HbA2 may be less accurate in SCT, these results suggest that HbA2 content may attenuate ESA resistance in this population, and further studies are needed to understand this relationship.Table 1Demographic and clinical data in 24 African-American hemodialysis patients with sickle cell trait.Age (yrs)62.1 (48.7, 69.2)Male sex (N, %)13 (54.2)Body mass index (kg/m2)26.1 (23.1, 30.7)Dialysis vintage (yrs)6.2 (2.9, 9.3)Diabetes (N, %)16 (66.7)Arteriovenous fistula (N,%)14 (58.3)Hemoglobin (gm/dl)11.9 (11.4, 12.5)HbS (%)35.8 (31.4, 38.4)HbA2 (%)4.1 (3.9, 4.4)Ferritin (ng/ml)831.3 (610.7, 1121.0)Iron saturation %29 (24.7, 37.2)iPTH (pg/ml)451.6 (269.3, 715.2)Albumin (mg/dl)4.0 (3.9, 4.1)Phosphorus (mg/ml)5.7 (4.6, 6.3)Dialysis adequacy (Kt/V)1.47 (1.35, 1.54)Counts presented as N (%). Continuous variables presented as Median and Interquartile Range (IQR) DisclosuresNo relevant conflicts of interest to declare.

Intravenous Iron Therapy in Patients with Idiopathic Pulmonary Arterial Hypertension and Iron Deficiency

In patients with idiopathic pulmonary arterial hypertension (iPAH), iron deficiency is common and has been associated with reduced exercise capacity and worse survival. Previous studies have shown beneficial effects of intravenous iron administration. In this study, we investigated the use of intravenous iron therapy in iron-deficient iPAH patients in terms of safety and effects on exercise capacity, and we studied whether altered exercise capacity resulted from changes in right ventricular (RV) function and skeletal muscle oxygen handling. Fifteen patients with iPAH and iron deficiency were included. Patients underwent a 6-minute walk test, cardiopulmonary exercise tests, cardiac magnetic resonance imaging, and a quadriceps muscle biopsy and completed a quality-of-life questionnaire before and 12 weeks after receiving a high dose of intravenous iron. The primary end point, 6-minute walk distance, was not significantly changed after 12 weeks (409 ± 110 m before vs. 428 ± 94 m after; P = 0.07). Secondary end points showed that intravenous iron administration was well tolerated and increased body iron stores in all patients. In addition, exercise endurance time (P < 0.001) and aerobic capacity (P < 0.001) increased significantly after iron therapy. This coincided with improved oxygen handling in quadriceps muscle cells, although cardiac function at rest and maximal [Formula: see text] were unchanged. Furthermore, iron treatment was associated with improved quality of life (P < 0.05). In conclusion, intravenous iron therapy in iron-deficient iPAH patients improves exercise endurance capacity. This could not be explained by improved RV function; however, increased quadriceps muscle oxygen handling may play a role. ( ClinicalTrials.gov identifier NCT01288651).

Understanding the Recent Increase in Ferritin Levels in United States Dialysis Patients: Potential Impact of Changes in Intravenous Iron and Erythropoiesis-Stimulating Agent Dosing.

Anemia management changed substantially among dialysis patients in the United States around the time of implementation of the new Centers for Medicare & Medicaid Services bundled payment system and erythropoiesis-stimulating agent (ESA) label change in 2011. Among these, average ferritin levels increased dramatically and have remained high since; this study sought to gain understanding of this sustained rise in ferritin levels. Trends in mean ferritin, hemoglobin, IV iron dose, and ESA dose from 2009 to 2013 were examined in 9735 patients from 91 United States Dialysis Outcomes and Practice Patterns Study facilities. Linear mixed models were used to assess the extent to which intravenous (IV) iron and ESA dose accounted for patients' changes in ferritin over time. Mean ESA dose and hemoglobin levels declined throughout the study. Mean IV iron dose increased from 210 mg/mo in 2009-2010 to a peak of 280 mg/mo in 2011, then declined back to 200 mg/mo and remained stable from 2012 to 2013. Mean ferritin increased from 601 ng/ml in the third quarter of 2009 to 887 ng/ml in the first quarter of 2012; models suggest that higher IV iron dosing was a primary determinant during 2011, but lower ESA doses contributed to the sustained high ferritin levels thereafter. In a subset of 17 facilities that decreased IV iron dose in 2011, mean ferritin rose by 120 ng/ml to 764 ng/ml, which appeared to be primarily due to ESA reduction. Together, changes in IV iron and ESA doses accounted for 46% of the increase in ferritin over the study period. In contrast to expectations, the rise in average IV iron dose did not persist beyond 2011. The sustained rise in ferritin levels in United States dialysis patients after policy changes in 2011, to average levels well in excess of 800 ng/ml, appeared to be partly due to reductions in ESA dosing and not solely IV iron dosing practices. The effect of these changes in ferritin on health outcomes requires further investigation.

Intravenous iron dose and mortality in hemodialysis patients

To the Editor: There is an important misunderstanding evident in the commentary by Weiss and Kronenberg1 addressing our article2 describing an association between high-dose intravenous iron and mortality in hemodialysis patients. The editorialists state that ‘patients receiving higher dosages of iron also received higher dosages of erythropoiesis-stimulating agent (ESA), pointing to bone marrow hyporesponsiveness. It is therefore also conceivable that higher ESA rather than increased iron dosages contribute to mortality in such subjects …’.1 As shown in Table 2 of the manuscript, however, even after adjustment for ESA dose and hemoglobin concentration, average monthly intravenous iron doses 400 mg/month were associated with significantly increased mortality compared with the most common doses of 100–199 mg/month (hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.0–1.28) and intravenous iron doses 300 mg/month were associated with significantly increased mortality compared with doses <300 mg/month (HR 1.10; 95% CI 1.03–1.17).2 It is therefore incorrect to ascribe to concomitant ESA administration the observed mortality risk associated with intravenous iron prescription. Also, the iron-associated mortality hazard ratios remained of similar magnitude and significance following further adjustment for transferrin saturation and serum ferritin concentration—it does not appear that iron dose was merely a reflection of inflammation as a proximate factor related to mortality. We reiterate our contention that well-powered clinical trials to evaluate the safety of different intravenous iron dosing strategies are urgently needed; we are pleased that the editorialists agreed on this point.

In This Issue

HomeCirculation ResearchVol. 116, No. 10In This Issue Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published8 May 2015https://doi.org/10.1161/RES.0000000000000056Circulation Research. 2015;116:1629Nonvenous Origin of Lymphatic Vessels (p 1649)Download figureDownload PowerPointMartinez-Corral et al discover that the mammalian lymphatic system doesn’t solely develop from blood vessels as previously thought.It is currently believed that during embryogenesis, lymph vessels arise from veins by the transdifferentiation of venous endothelial cells into lymphatic endothelial cells (LECs). However, research in chickens and frogs suggests LECs could also be derived from a secondary source. Martinez-Corral and colleagues have now found evidence of a nonvenous source of LECs in mammals as well. They showed that in the lumbar region of embryonic mice, dermal lymph vessels arise independently from subcutaneous vessels, suggesting the two might have different origins. To confirm this suspicion, they performed lineage tracing experiments, in which they genetically labeled venous endothelial cells—identified by expression of the protein Tie2—such that the cells and all their progeny would fluoresce green. They found, however, that many LECs were not fluorescent, indicating that they had not arisen solely from these venous endothelial cells. The team also showed that deleting a critical LEC driver—Prox1—specifically from the Tie2 lineage, did not eliminate all LECs, providing further evidence of an alternative orgin. These findings increase our understanding of the origins of lymphatic vessels, which could potentially aid the development of new therapeutic lymphatic regeneration approaches in the future.CIRP Regulates Cardiac Repolarization (p 1655)Download figureDownload PowerPointLi et al find that cold-induced RNA binding protein regulates repolarization of the heart.The Cold-Induced RNA binding Protein (CIRP) is rapidly upregulated in response to stresses such as low temperature, hypoxia, and UV exposure, but the protein has also been implicated in a number of physiological processes such as circadian regulation of gene expression and proinflammatory responses. Li and colleagues have now investigated the function of CIRP in the heart. The team engineered rats in which the gene encoding CIRP was homozygously deleted and found that the animals’ hearts exhibited a distinctly reduced QT interval—the time it takes for electrical depolarization and repolarization during a single heartbeat. The team went on to show that this unusual electrical activity in the knockout mice was associated with an increase in the expression of the subunits of the potassium channel that contribute to the repolarization of the heart. They also showed that in normal cells CIRP bound to the mRNAs of these channel subunits—most likely suppressing their expression. The finding that CIRP regulates repolarization of the heart provides new understanding of the electrophysiological mechanisms at work both during normal functioning of the heart as well as under pathological conditions such as arrhythmia.Iron Deficiency and Pulmonary Hypertension (p 1680)Download figureDownload PowerPointIron deficiency promotes the development of pulmonary hypertension in rats, report Cotroneo et al.Patients with pulmonary hypertension commonly exhibit low iron levels in the blood, and such iron deficiency is associated with poorer disease prognoses. However, whether iron deficiency contributes to or is merely a consequence of pulmonary hypertension is a matter of debate. Controneo and colleagues now present evidence suggesting that iron deficiency alone can promote pulmonary hypertension, at least in rats. To examine the role of iron-deficiency, Controneo and colleagues restricted the dietary iron intake in otherwise healthy rats and found that over the course of four weeks the animals developed multiple symptoms of pulmonary hypertension including increased pulmonary blood pressure, right ventricular hypertrophy, enlargement of the heart, infiltration of inflammatory cells, and a profound remodeling of the pulmonary vasculature—with blood vessels displaying smaller lumens and hypertrophy of the walls. They also noted altered metabolic activity in pulmonary vessels—such as increased glucose uptake and reduced mitochondrial activity—suggesting a switch from aerobic to anaerobic respiration. When the rats were given a dose of intravenous iron, however, these symptoms were reversed. Based on these observations, the authors suggest that ongoing clinical evaluations of iron supplementation in pulmonary hypertension patients could yield promising results. Previous Back to top Next FiguresReferencesRelatedDetails May 8, 2015Vol 116, Issue 10 Advertisement Article InformationMetrics © 2015 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000056 Originally publishedMay 8, 2015 PDF download Advertisement

A 1-year trial of repeated high-dose intravenous iron isomaltoside 1000 to maintain stable hemoglobin levels in inflammatory bowel disease

Objective. Iron isomaltoside 1000 (Monofer®) is a high-dose intravenous (IV) iron, which in a recent 8 weeks trial in inflammatory bowel disease (IBD) subjects with iron deficiency anemia (IDA) demonstrated good tolerability and efficacy. The present trial is an extension to this trial, which evaluates the need for additional high IV iron doses to maintain a stable hemoglobin (Hb) ≥12.0 g/dl. Material and methods. This was a prospective, open-label, 12 months trial of European IBD subjects willing to participate after completing the lead-in trial. Subjects were allowed re-dosing with 500–2000 mg single doses of iron isomaltoside 1000 infused over ∼15 min at 3 months intervals depending on a predefined algorithm. Outcome measures included Hb, safety parameters and need for additional iron dosing. Results. A total of 39 subjects were enrolled of which 34 subjects required re-dosing with a median cumulative 1-year dose of 1.8 g (mean cumulative dose 2.2 g). The mean (SD) Hb was 12.3 (1.5) g/dl at baseline, 12.8 (1.6) g/dl at 3 months, 12.8 (1.6) g/dl at 6 months, 12.9 (1.4) g/dl at 9 months and 12.9 (1.6) g/dl at 12 months. Seventy-four percent of subjects who had an Hb ≥12.0 g/dl at baseline were able to maintain Hb ≥12.0 g/dl till the end of the trial at 12 months. Nonserious probably related hypersensitivity reactions without significant hypotension were reported at the beginning of the infusion in two subjects, who recovered without sequelae. Conclusion. Repeated treatment of iron deficiency with iron isomaltoside 1000 could avoid episodes of IDA without major safety issues.Trial registration: ClinicalTrial.gov identifier: NCT01410435.

P339. High dose intravenous iron isomaltoside 1000 in subjects with inflammatory bowel disease - the PROMISE trial

P339. High dose intravenous iron isomaltoside 1000 in subjects with inflammatory bowel disease - the PROMISE trial

Data from the Dialysis Outcomes and Practice Patterns Study validate an association between high intravenous iron doses and mortality

Intravenous (IV) iron is required for optimal management of anemia in the majority of hemodialysis (HD) patients. While IV iron prescription has increased over time, the best dosing strategy is unknown and any effect of IV iron on survival is unclear. Here we used adjusted Cox regression to analyze associations between IV iron dose and clinical outcomes in 32,435 HD patients in 12 countries from 2002 to 2011 in the Dialysis Outcomes and Practice Patterns Study. The primary exposure was total prescribed IV iron dose over the first 4 months in the study, expressed as an average dose/month. Compared with 100-199 mg/month (the most common dose range), case-mix-adjusted mortality was similar for the 0, 1-99, and 200-299 mg/month categories but significantly higher for the 300-399 mg/month (HR of 1.13, 95% CI of 1.00-1.27) and 400 mg/month or more (HR of 1.18, 95% CI of 1.07-1.30) groups. Convergent validity was proved by an instrumental variable analysis, using HD facility as the instrument, and by an analysis expressing IV iron dose/kg body weight. Associations with cause-specific mortality (cardiovascular, infectious, and other) were generally similar to those for all-cause mortality. The hospitalization risk was elevated among patients receiving 300 mg/month or more compared with 100-199 mg/month (HR of 1.12, 95% CI of 1.07-1.18). In light of these associations, a well-powered clinical trial to evaluate the safety of different IV iron-dosing strategies in HD patients is urgently needed.

Intravenous Iron Therapy in Patients with Iron Deficiency Anemia: Dosing Considerations.

Objective. To provide clinicians with evidence-based guidance for iron therapy dosing in patients with iron deficiency anemia (IDA), we conducted a study examining the benefits of a higher cumulative dose of intravenous (IV) iron than what is typically administered. Methods. We first individually analyzed 5 clinical studies, averaging the total iron deficit across all patients utilizing a modified Ganzoni formula; we then similarly analyzed 2 larger clinical studies. For the second of the larger studies (Study 7), we also compared the efficacy and retreatment requirements of a cumulative dose of 1500 mg ferric carboxymaltose (FCM) to 1000 mg iron sucrose (IS). Results. The average iron deficit was calculated to be 1531 mg for patients in Studies 1–5 and 1392 mg for patients in Studies 6-7. The percentage of patients who were retreated with IV iron between Days 56 and 90 was significantly (p < 0.001) lower (5.6%) in the 1500 mg group, compared to the 1000 mg group (11.1%). Conclusions. Our data suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in a majority of patients with IDA and a dose of 1500 mg is closer to the actual iron deficit in these patients.

A Comparative Study to Evaluate the Efficacy and Safety of Single Dose Intravenous Iron Carboxymaltose vs Multidose Iron Sucrose in Postpartum Cases of Severe Iron Deficiency Anemia

ABSTRACT Objective To evaluate the efficacy and safety of single dose intravenous iron carboxymaltose vs multidose iron sucrose in postpartum cases of severe iron deficiency anemia. Materials and methods One hundred cases with iron deficiency anemia in postpartum patient were selected from postpartum wards and assigned in two groups of 50 each. In group A, iron carboxymaltose injection administered by intravenous infusion upto a maximum single dose of 20 ml of iron carboxymaltose injection (1000 mg of iron). In group B Iron sucrose was given as 200 mg elemental iron (2 ampules of 5 ml) in 100 ml of 0.9% normal saline infusion over 15 minute alternate days up to 5 days. All the patients were monitored for rise in hemoglobin level at 2, 4, 8 and 12 weeks of iron therapy, adverse effect and rise in hematological parameter at 4 weeks. Results In group A, mean Hb level rise is 3.95 g/dl and in group B, it is 3.32 g/dl at 4 weeks of initial therapy. In group A, 100% cases achieved target Hb at 12 weeks after therapy while in group B 98% cases achieved target Hb at 12 weeks after therapy. In group A, 12% cases have grade 1 adverse reaction while in group B, 20% cases have adverse reaction. Conclusion Administration of intravenous iron has a good clinical result, with minimum adverse reactions. Thus, we can conclude that intravenous iron carboxymaltose therapy is safe, convenient, more effective and faster acting than intravenous iron sucrose for treatment of severe iron deficiency anemia in postpartum patient. How to cite this article Garg R, Singh S, Singh S, Rajvanshi R. A Comparative Study to Evaluate the Efficacy and Safety of Single Dose Intravenous Iron Carboxymaltose vs Multidose Iron Sucrose in Postpartum Cases of Severe Iron Deficiency Anemia. J South Asian Feder Obst Gynae 2015;7(1):18-21.

Intravenous iron exposure and mortality in patients on hemodialysis.

Clinical trials assessing effects of larger cumulative iron exposure with outcomes are lacking, and observational studies have been limited by assessment of short-term exposure only and/or failure to assess cause-specific mortality. The associations between short- and long-term iron exposure on all-cause and cause-specific mortality were examined. The study included 14,078 United States patients on dialysis initiating dialysis between 2003 and 2008. Intravenous iron dose accumulations over 1-, 3-, and 6-month rolling windows were related to all-cause, cardiovascular, and infection-related mortality in Cox proportional hazards models that used marginal structural modeling to control for time-dependent confounding. Patients in the 1-month model cohort (n=14,078) were followed a median of 19 months, during which there were 27.6% all-cause deaths, 13.5% cardiovascular deaths, and 3% infection-related deaths. A reduced risk of all-cause mortality with receipt of >150-350 (hazard ratio, 0.78; 95% confidence interval, 0.64 to 0.95) or >350 mg (hazard ratio, 0.79; 95% confidence interval, 0.62 to 0.99) intravenous iron compared with >0-150 mg over 1 month was observed. There was no relation of 1-month intravenous iron dose with cardiovascular or infection-related mortality and no relation of 3- or 6-month cumulative intravenous iron dose with all-cause or cardiovascular mortality. There was a nonstatistically significant increase in infection-related mortality with receipt of >1050 mg intravenous iron in 3 months (hazard ratio, 1.69; 95% confidence interval, 0.87 to 3.28) and >2100 mg in 6 months (hazard ratio, 1.59; 95% confidence interval, 0.73 to 3.46). Among patients on incident dialysis, receipt of ≤ 1050 mg intravenous iron in 3 months or 2100 mg in 6 months was not associated with all-cause, cardiovascular, or infection-related mortality. However, nonstatistically significant findings suggested the possibility of infection-related mortality with receipt of >1050 mg in 3 months or >2100 mg in 6 months. Randomized clinical trials are needed to assess the safety of exposure to greater cumulative intravenous iron doses.

Has dialysis payment reform led to initial racial disparities in anemia and mineral metabolism management?

Implementation of the Medicare ESRD prospective payment system (PPS) and changes to dosing guidelines for erythropoiesis-stimulating agents (ESAs) in 2011 appear to have influenced use of injectable medications among dialysis patients. Given historically higher ESA and vitamin D use among black patients, we assessed the effect of these policy changes on racial disparities in the management of anemia and mineral metabolism. Analyses used cross-sectional monthly cohorts for a period-prevalent sample of 7384 maintenance hemodialysis patients at 132 facilities from the Dialysis Outcomes and Practice Patterns Study (DOPPS) Practice Monitor. Linear splines with knots at each policy change were used in survey-weighted regressions to estimate time trends in hemoglobin (Hgb), erythropoietin (EPO) dose, intravenous (IV) iron dose, ferritin, transferrin saturation (TSAT) concentration, parathyroid hormone (PTH), IV vitamin D dose, cinacalcet use, and phosphate binder use. From August 2010 to December 2011, mean Hgb declined from 11.5 to 11.0 g/dl (P<0.001), mean EPO dose declined from 20,506 to 14,777 U/wk (P<0.001), and mean serum PTH increased from 340 to 435 pg/ml (P<0.001). No meaningful differences by race were observed regarding the rates of change of management practices or laboratory measures (all P>0.21). Mean EPO and vitamin D dose and serum PTH levels remained higher in blacks. Despite evidence that anemia and mineral metabolism management practices have changed significantly over time, there was no immediate indication of racial disparities resulting from implementation of the PPS or ESA label change. Further studies are needed to examine effects among patient and facility subgroups.

Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients.

In recent times, therapy for renal anemia has changed dramatically in that iron administration has increased and doses of erythropoiesis-stimulating agents (ESAs) have decreased. Here we used a prospective, observational, multicenter design and measured the serum ferritin and hemoglobin levels every 3 months for 2 years in 1086 patients on maintenance hemodialysis therapy. The associations of adverse events with fluctuations in ferritin and hemoglobin levels and ESA and iron doses were measured using a Cox proportional hazards model for time-dependent variables. The risks of cerebrovascular and cardiovascular disease (CCVD), infection, and hospitalization were higher among patients who failed to maintain a target-range hemoglobin level and who exhibited high-amplitude fluctuations in hemoglobin compared with patients who maintained a target-range hemoglobin level. Patients with a higher compared with a lower ferritin level had an elevated risk of CCVD and infectious disease. Moreover, the risk of death was significantly higher among patients with high-amplitude ferritin fluctuations compared with those with a low ferritin level. The risks of CCVD, infection, and hospitalization were significantly higher among patients who were treated with high weekly doses of intravenous iron compared with no intravenous iron. Thus, there is a high risk of death and/or adverse events in patients with hemoglobin levels outside the target range, in those with high-amplitude hemoglobin fluctuations, in those with consistently high serum ferritin levels, and in those with high-amplitude ferritin fluctuations.

Acceleration of iron utilization after intravenous iron administration during activated erythropoiesis in hemodialysis patients: a randomized study.

This study aimed to evaluate the effect of different timings of iron administration during erythropoiesis activated by continuous erythropoietin receptor activator (CERA) on reticulocyte iron uptake in hemodialysis patients. In total, 110 patients were randomized to receive 40 mg intravenous elemental iron doses at all three hemodialysis sessions in the first week (IW1 group: n = 57) or in the third week (IW3 group: n = 53) after CERA administration. Following CERA administration at day 0, reticulocyte count increased, peaking at day 7. At days 7 and 14, the observed changes in Ret-He were higher in the IW1 group than in the IW3 group. Increases in total reticulocyte hemoglobin at day 7 were higher in the IW1 group than in the IW3 group. In contrast, there was only tendency toward greater total reticulocyte hemoglobin after iron administration in the third week in the IW3 group. Intravenous iron supplementation in the first week of CERA administration increases reticulocyte iron uptake; however, iron supplementation in the third week does not. The findings indicate that iron should be intravenously administered to increase the efficacy of CERA within 1 week of CERA administration during highly active erythropoiesis.

Effects of Crit-Line® Monitor Use on Patient Outcomes and Epoetin Alfa Dosing following Onset of Hemodialysis: A Propensity Score-Matched Study

Background: The Crit-Line® monitor (CLM) is a device for monitoring hematocrit, oxygen saturation and change in intravascular blood volume during hemodialysis. Prior studies have evaluated CLM use in dialysis patients, but not specifically in those new to dialysis. Methods: In this retrospective analysis, 199 patients initiating dialysis at 8 facilities routinely using CLM were compared with 796 propensity score-matched non-CLM patients initiating dialysis at facilities not using CLM. Outcomes were considered over the first 180 days on dialysis. Results: Overall, the CLM group had higher StdKt/V (p = 0.06) and received lower doses of intravenous iron than the non-CLM group (p < 0.001). Erythropoiesis-stimulating agent doses were lower in the CLM group in months 1-5. Serum iron and transferrin saturation levels were higher overall for the CLM group than the non-CLM group (p = 0.004 and 0.01, respectively). Hemoglobin levels and time to first hospitalization were similar for both groups. Conclusion: Use of CLM is associated with lower erythropoiesis-stimulating agent and iron use in incident hemodialysis patients.

Long-Term Safety and Efficacy of a Novel Iron-Containing Phosphate Binder, JTT-751, in Patients Receiving Hemodialysis

ObjectiveJTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient. This study investigated long-term safety and efficacy of JTT-751 for hyperphosphatemia in patients receiving hemodialysis. Design and MethodsThis was 52-week, phase 3, multicenter, open-label, dose titration, long-term study. All patients were receiving thrice-weekly hemodialysis for ≥3 months before the initiation of the study. JTT-751 was given at titrated doses between 1.5 and 6.0 g/day. Main Outcome MeasuresSafety endpoints were adverse events and adverse drug reactions. Efficacy outcomes were the change in serum phosphate, corrected serum calcium, and intact parathyroid hormone. Changes in ferritin, transferrin saturation, and doses of erythropoiesis-stimulating agents (ESAs) and intravenous iron formulations were additional outcomes. ResultsOne hundred and eighty patients were included in the trial. Dose-titrated JTT-751 decreased mean serum phosphate after administration and satisfactorily maintained serum phosphate concentrations throughout the entire duration of the 52-week trial. Mean serum phosphate concentrations were kept lower than 5.5 mg/dL from weeks 5 to 52. The most common adverse events were gastrointestinal disorders, which were mild to moderate in intensity. Serum ferritin concentrations rose to a peak around week 28 and stabilized thereafter. The mean intravenous iron dose decreased from 57.3 mg/4 weeks (weeks 0-12) to 3.6 mg/4 weeks (weeks 28-52); weekly ESA dose declined by 25% over the same time frame, while mean hemoglobin concentrations remained stable. ConclusionJTT-751 1.5-6.0 g/day controls serum phosphorus concentrations and reduces the need for ESAs and intravenous iron in patients receiving hemodialysis.

Anemia Management Trends in Hospital-Based Dialysis Centers (HBDCs), 2010 to 2013

BackgroundFew data have been reported on anemia management practices in hospital-based dialysis centers (HBDCs), which are uniquely different from other freestanding dialysis centers. Examining data from HBDCs would help determine if HBDCs and the general US dialysis population have similar trends related to how anemia is managed in dialysis patients. ObjectiveGiven recent changes in the prescribing information of erythropoiesis-stimulating agents (ESAs) and in end-stage renal disease–related health policy and reimbursement, this study describes trends in anemia management practices in HBDCs from January 2010 through March 2013. MethodsElectronic medical records of 5404 adult hemodialysis patients in 50 US-based HBDCs were analyzed retrospectively. Patients included in the study cohort were aged ≥18 years and had at least 1 hemoglobin (Hb) measurement and 1 dose of an ESA between January 2010 and March 2013. End points included Hb concentration, darbepoetin alfa dosing, epoetin alfa dosing, and iron biomarkers (transferrin saturation and ferritin) and dosing. ResultsFrom 2010 to 2013, mean monthly Hb levels declined from 11.4 to 10.7 g/dL; the percentage of patients with mean monthly Hb levels <10 g/dL increased from 11.3% to 24.4%; and the percentage of patients with mean monthly Hb levels >12 g/dL declined from 30.1% to 11.2%. The median darbepoetin alfa cumulative 4-week dose also declined 38.8%, and the weekly epoetin alfa dose declined 24%. From January 2010 to March 2013, the percentage of patients with transferrin saturation >30% increased from 35.8% to 43.6%, the percentage of patients with ferritin levels >500 ng/mL increased from 62.0% to 77.9%, the percentage of patients with ferritin levels ≥800 ng/mL increased from 28.9% to 47.3%, and the median cumulative 4-week intravenous iron dose increased 50%. ConclusionsThese study results support growing evidence that meaningful changes have occurred over the last 3 years in how anemia is clinically managed in US hemodialysis patients. Study limitations include that changes in patient clinical/demographic characteristics over time were not controlled for and that study findings may not be applicable to HBDCs that have different patient populations and/or do not use an electronic medical record system. Continuing to evaluate anemia management practices in HBDCs would provide additional information on the risks and benefits of anemia care. Consistent with national data, the findings from this study indicate that from 2010 to 2013, HBDCs modified anemia management practices for dialysis patients, as evidenced by reductions in mean monthly Hb levels and ESA dosing and by increases in iron biomarkers and dosing.

Potential effects of omega-3 fatty acids on anemia and inflammatory markers in maintenance hemodialysis patients

BackgroundAnemia is a common complication among hemodialysis (HD) patients. Although intravenous iron and erythropoiesis-stimulating agents revolutionized anemia treatment, about 10% of HD patients show suboptimal response to these agents. Systemic inflammation and increased serum hepcidin level may contribute to this hyporesponsiveness. Considering the anti-inflammatory properties of omega-3 fatty acids, this study aimed to evaluate potential role of these fatty acids in improving anemia and inflammation of chronic HD patients.MethodsIn this randomized, placebo-controlled trial, 54 adult patients with HD duration of at least 3 months were randomized to ingest 1800 mg of either omega-3 fatty acids or matching placebo per day for 4 months. Anemia parameters including blood hemoglobin, serum iron, transferrin saturation (TSAT), erythropoietin resistance index, and required dose of intravenous iron and erythropoietin, and serum concentrations of inflammatory/anti-inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, C-reactive protein (CRP), hepcidin, ferritin, intact parathyroid hormone (iPTH), and ratios of IL-10 to IL-6 and IL-10 to TNF-α were measured at baseline and after 4 months of the intervention.Results45 subjects (25 in the omega-3 and 20 in the placebo group) completed the study. No significant changes were observed in blood hemoglobin, serum iron, TSAT, and required dose of intravenous iron in either within or between group comparisons. Additionally, erythropoietin resistance index as well as required dose of intravenous erythropoietin showed no significant change in the omega-3 group compared to the placebo group. Although a relative alleviation in inflammatory state appeared in the omega-3 group, the mean differences of inflammatory and anti-inflammatory markers between the two groups did not reach statistically significant level except for IL-10-to-IL-6 ratio and serum ferritin level which showed significant changes in favor of omega-3 treatment (P <0.001 and P = 0.003, respectively).ConclusionOmega-3 fatty acids relatively improved systemic inflammation of chronic HD patients without any prominent benefits on anemia. However, future well-designed studies on larger number of patients may determine utility of omega-3 fatty acids in HD patients with respect to inflammation and anemia.