SP369THE TARGET HB CONTENT OF RETICULOCYTE (CHR) VALUE FOR EFFICIENT ANEMIA IMPROVEMENT ON HEMODIALYSIS PATIENTS TREATED WITH DARBEPOETIN ALFA IS ACHIEVED BY LOW FERRITIN LEVEL AND MODERATE TRANSFERRIN SATURATION

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Chie Ogawa ◽  
Ken Tsuchiya ◽  
Naohisa Tomosugi ◽  
Fumiyoshi Kanda ◽  
Kunimi Maeda
Keyword(s):  
Darbepoetin Alfa ◽  
Ferritin Level ◽  
Transferrin Saturation ◽  
Hemodialysis Patients

scholarly journals Safety and efficacy of low-dose subcutaneous erythropoietin in hemodialysis patients.

1997 ◽  
Vol 8 (2) ◽  
pp. 288-293
Author(s):  
K P Parker ◽  
W E Mitch ◽  
J C Stivelman ◽  
E J Macon ◽  
J L Bailey ◽  
...  
Keyword(s):  
Low Dose ◽  
Ferritin Level ◽  
Transferrin Saturation ◽  
Hemodialysis Patients ◽  
Control Group ◽  
Dialysis Session ◽  
Phase 2 ◽  
Safety And Efficacy ◽  
Control Subjects ◽  
And Control

Anemia in hemodialysis patients is effectively treated by intravenous (IV) injections of recombinant human erythropoietin (rHuEPO) at each dialysis session. Because the hormone is effective by subcutaneous (SC) administration, it was decided that this study would evaluate low-dose weekly SC rHuEPO therapy. To determine the safety and efficacy of weekly SC rHuEPO administration to hemodialysis patients, only one third the weekly IV dose was given and the effects were compared with those from an age-, gender-, and nephrologic disease-matched control group treated in the standard fashion. Forty-four patients entered the trial and 27 completed the protocol along with 27 control subjects. During Phase 1, experimental and control subjects received standard IV rHuEPO at dialysis for 6 months. During Phase 2, experimental patients received weekly SC rHuEPO at one third the weekly IV dose for 10 months; control subjects continued to receive IV therapy. In Phase 3, both groups were treated for 6 more months with IV rHuEPO. In Phase 2, there was no significant reduction in hematocrit value, reticulocyte count, transferrin saturation, or ferritin level in the experimental group, even with only one third the weekly rHuEPO IV dose over the 10-month period. There were no significant differences between IV and SC rHuEPO administration or between experimental and control subjects in blood pressure, serum chemistries, or parameters of "dialysis adequacy." It was concluded that low-dose weekly SC rHuEPO administration is a safe and effective method for maintaining the hematocrit level of stable hemodialysis patients. This therapy could enhance the efficacy of rHuEPO and substantially reduce costs while preserving patient care outcomes.

scholarly journals Skeletal muscle mass is associated with erythropoietin response in hemodialysis patients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tomoaki Takata ◽  
Yukari Mae ◽  
Kentaro Yamada ◽  
Sosuke Taniguchi ◽  
Shintaro Hamada ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Linear Regression Analysis ◽  
Transferrin Saturation ◽  
Resistance Index ◽  
Hemodialysis Patients ◽  
Maintenance Hemodialysis ◽  
Weekly Dose

Abstract Background Hyporesponsiveness to erythropoietin stimulating agent (ESA) is associated with poor outcomes in patients with chronic kidney disease. Although ESA hyporesponsiveness and sarcopenia have a common pathophysiological background, clinical evidence linking them is scarce. The purpose of the study was to investigate the relationship between ESA responsiveness and skeletal muscle mass in hemodialysis patients. Methods This cross-sectional study analyzed 70 patients on maintenance hemodialysis who were treated with ESA. ESA responsiveness was evaluated by erythropoietin resistance index (ERI), calculated as a weekly dose of ESA divided by body weight and hemoglobin (IU/kg/week/dL), and a weekly dose of ESA/hemoglobin (IU/week/dL). A dose of ESA is equivalated to epoetin β. Correlations between ESA responsiveness and clinical parameters including skeletal muscle mass were analyzed. Results Among the 70 patients, ERI was positively correlated to age (p < 0.002) and negatively correlated to height (p < 0.001), body weight (p < 0.001), BMI (p < 0.001), skeletal muscle mass (p < 0.001), transferrin saturation (TSAT) (p = 0.049), and zinc (p = 0.006). In the multiple linear regression analysis, TSAT, zinc, and skeletal muscle mass were associated with ERI and weekly ESA dose/hemoglobin. Conclusions Skeletal muscle mass was the independent predictor for ESA responsiveness as well as TSAT and zinc. Sarcopenia is another target for the management of anemia in patients with hemodialysis.

Switch From Epoetin Beta to Darbepoetin Alfa Treatment of Anemia in Taiwanese Hemodialysis Patients: Dose Equivalence by Hemoglobin Stratification

2016 ◽  
Vol 20 (4) ◽  
pp. 400-407
Author(s):  
Shang-Chih Liao ◽  
Cheng-Chieh Hung ◽  
Chien-Te Lee ◽  
Chih-Hsiung Lee ◽  
Chin-Chan Lee ◽  
...  
Keyword(s):  
Darbepoetin Alfa ◽  
Hemodialysis Patients ◽  
Epoetin Beta

scholarly journals Role of Roxadustat in Improving Erythropoiesis-Stimulating Agent (ESA)-Resistant Anemia in Patients on Maintenance Hemodialysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-47
Author(s):  
Satoshi Funakoshi
Keyword(s):  
Iron Metabolism ◽  
Conflicts Of Interest ◽  
Hypoxia Inducible Factor ◽  
Transferrin Saturation ◽  
Hemodialysis Patients ◽  
Maintenance Hemodialysis ◽  
Reactive Protein ◽  
Study Results ◽  
Dialysis Vintage ◽  
Patients With Diabetes

Background: Roxadustat, an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, is shown to stimulate erythropoiesis thus improving iron metabolism. Again, while hyperglycemic states are known to be associated with a decreased tissue hypoxia response, to date, roxadustat has not been revaluated for its role in improving anemia in patients with or without diabetes in clinical settings. Methods: A total of 64 hemodialysis patients being treated with epoetin α (9000 units weekly) participated in the study after giving informed consent. They were switched from intravenous epoetin α to oral roxadustat (100 mg 3 times weekly) therapy and were assessed 8 weeks later for improvements in anemia, as well as for changes in parameters for iron metabolism and C-reactive protein (CRP). Results: The study included 39 patients without diabetes (mean age, 71.1 ± 12.1 years; mean dialysis vintage, 7.5 ± 7.4 years; mean GA, 16.2 ± 2.9%) and 27 patients with diabetes (mean age, 70.3 ± 10.3 years; mean dialysis vintage, 5.9 ± 5.5 years; mean GA, 24.9 ± 5.5%). As shown in Table, after 8 weeks the Hb concentration was significantly increased from 10.3 ± 0.8 g/dL at baseline to 10.7 ± 1.3 g/dL in patients without diabetes (P = 0.03) but was not increased in patients with diabetes (from 10.4 ± 0.6 at baseline to 10.5 ± 1.1 g/dL). Again, the serum iron, ferritin concentrations and the transferrin saturation ratio were decreased, irrespective of whether or not they had diabetes, with no change shown in serum CRP level. Conclusion: Switching hemodialysis patients with ESA-resistant anemia from ESA to roxadustat led to improvements in anemia only in those without diabetes, while study results suggested the involvement of mechanisms, other than impaired iron utilization or inflammation, in the impairment of hematopoiesis in those with diabetes. Table Disclosures No relevant conflicts of interest to declare.

MO559ASCEND-ND: STUDY DESIGN AND BASELINE CHARACTERISTICS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Vlado Perkovic ◽  
Allison Blackorby ◽  
Borut Cizman ◽  
Kevin Carroll ◽  
Alexander Cobitz ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Darbepoetin Alfa ◽  
Trial Design ◽  
Rescue Therapy ◽  
Transferrin Saturation ◽  
Statistical Testing ◽  
Efficacy And Safety ◽  
Primary Endpoints ◽  
History Of ◽  
Baseline Characteristics

Abstract Background and Aims The Anemia Study in Chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor (PHI) Daprodustat-Non-Dialysis (ASCEND-ND; NCT02876835) trial is evaluating the efficacy and safety of daprodustat when compared with darbepoetin alfa in CKD patients with anaemia not requiring dialysis. We report the trial design as well as key baseline characteristics of participants. Method Eligible patients from 39 countries were adults with CKD stages 3–5 who were able to provide informed consent and demonstrated adherence to daprodustat placebo tablets and study procedures during the run-in period. Patients were eligible if (1) they were not using erythropoiesis stimulating agents (ESAs) and had a screening haemoglobin (Hb) 8 to 10 g/dL or if (2) they were receiving ESAs with screening Hb of 8 to 12 g/dL. Patients were required to be iron replete [transferrin saturation (TSAT) &gt;20% and serum ferritin &gt;100 ng/mL] at screening. Participants were randomised to daprodustat or darbepoetin alfa (1:1) in an open-label (sponsor-blind) trial design with blinded endpoint assessment. An IDMC conducts regular reviews of unblinded safety and efficacy data and makes recommendations for additions or adjustments. An external, independent and blinded Clinical Events Classification (CEC) group, led by the Duke Clinical Research Institute, in collaboration with George Clinical, adjudicate predefined events. During the study, both groups had randomised treatment adjusted using a protocol-defined algorithm targeting a Hb range of 10 to 11 g/dL. Participants also followed protocol-defined iron management criteria to ensure they remained iron replete. Additionally, an anaemia rescue algorithm was in place to minimise the risk of extended periods of inadequate Hb response and to ensure consistent application of rescue therapy across the study. The co-primary endpoints are mean change in Hb between baseline and Evaluation Period (EP; Weeks 28 to 52, inclusive) and time to first adjudicated major adverse cardiovascular event (MACE; composite of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke). The study has more than 99% power for the Hb non-inferiority (NI) test with an NI margin of -0.75 g/dL for the treatment difference of mean change in Hb between baseline and EP, and approximately 90% power to exclude the NI margin of 1.25 for time to first adjudicated MACE, for daprodustat compared with darbepoetin alfa. Conditional on both co-primary endpoints achieving NI at the one-sided 2.5% level, statistical testing will progress to evaluate MACE and the principal secondary endpoint of CKD progression for superiority. These tests will be multiplicity adjusted. Results A total of 3872 patients were randomised (median age 67 years, 56% female; 55% white, 28% Asian, and 10% black). The median baseline Hb was 9.8 g/dL, serum ferritin was 274 ng/mL, TSAT 30%, and eGFR 18 mL/min/1.73 m2. Among randomised patients, 54% were ESA non-users, 57% reported a history of diabetes mellitus and 36% a history of cardiovascular disease. Median blood pressure was 135/74 mmHg. Sixty percent of participants were taking angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, while 57% were taking lipid modifying agents at baseline. The trial is expected to complete during 2021. Conclusion ASCEND-ND will define the efficacy and safety of daprodustat compared with darbepoetin alfa in the treatment of patients with anaemia associated with CKD not requiring dialysis.

P1407LIVER, HEART AND BONE: THE PATH OF IRON OVERLOAD IN HEMODIALYSIS PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Lucas Acatauassu Nunes ◽  
Luciene Reis ◽  
Hanna Machado ◽  
Rosse Osório ◽  
Rosa Moyses ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Remodeling ◽  
Serum Ferritin ◽  
Bone Biopsy ◽  
Saturation Index ◽  
Transferrin Saturation ◽  
Hemodialysis Patients ◽  
High Serum ◽  
Cross Sectional ◽  
Osteoblast Activity

Abstract Background Chronic kidney disease (CKD) is associated with several comorbidities, including anemia, since with decreased renal function there is a decrease in erythropoietin (EPO) production and changes in iron (Fe) metabolism. In hemodialysis patients, prescription of Fe is indicated to supplement the needs of this element by maintaining ferritin levels above 100 mg/dl and transferrin saturation greater than 20%. However, the excess of Fe can generate free Fe not bound to transferrin, and deposit in organs such as liver, heart, and bone marrow, with consequent impairment of their function. In hemodialysis patients, the diagnosis of Fe overload, its clinical significance and therapeutic decision have been poorly studied, unlike thalassemia patients. Aims To assess whether hemodialysis patients with ferritin levels equal to or greater than 1000 mg/l also have Fe overload in liver, heart, and bone marrow, as well as compromise bone density and remodeling. Method This is a cross-sectional analysis that included 28 adult patients on regular conventional hemodialysis. Inclusion criteria were serum levels of ferritin ≥ 1000 mg/l, and ESRD treated by regular hemodialysis for at least 6 months. We excluded patients with HIV, cancer, hepatic disease, patients who received desferroxamine in the latest year, and those previously submitted to a kidney transplant. All patients underwent dual-energy X-ray absorptiometry (DXA), serum ferritin, transferrin saturation index (STI), Fe, C reactive protein (CRP), Calcium(Ca), phosphorus (P), parathyroid hormone (PTH) and alkaline phosphatase (AP) levels were recorded. T2* image acquisition of Magnetic Resonance Imaging (MRI) 1,5 Tesla, were used for the assessment of Fe of liver, and heart. R2* and R2* Water were used of liver and bone (iliac crest). Bone biopsy was also performed. Results We evaluated 28 hemodialysis patients with a mean age of 55.8±13.1, hemodialysis time of 42.5±26.5 and iron use in the year prior to study enrollment of 311.5±179.8 mg/month. Biochemical analysis showed 3 patients with Hb below 9.0 mg/dl and 14 with values above 11.5 mg/dl; 6 patients with SatFe &lt;30% and 12 patients with ferritin &gt;1500mg/dl; 16 patients with PTH &lt;300pg/ml and eight with &gt;600pg/dl. MRI revealed Fe overload in the liver and bone tissue (figure 1) of all patients but not in the heart. Serum ferritin levels correlated with liver and bone overload (figure 2). Densitometry and bone biopsy results were not affected by Fe overload, however, serum Fe levels were associated with lower bone remodeling and mineralization suggesting an effect of this element on osteoblast activity. Conclusion High serum ferritin is associated with liver and bone marrow Fe overload, but not heart, as well as with low bone remodeling and mineralization. We must be aware of these side effects of high doses of Fe that are commonly used in these patients.

scholarly journals Monitoring of iron status in patients with heart failure

2019 ◽  
Vol 21 (Supplement_M) ◽  
pp. M32-M35 ◽  
Author(s):  
Ewa A Jankowska ◽  
Michał Tkaczyszyn ◽  
Marcin Drozd ◽  
Piotr Ponikowski
Keyword(s):  
Heart Failure ◽  
Iron Deficiency ◽  
Serum Ferritin Level ◽  
Iron Status ◽  
Ferritin Level ◽  
Transferrin Saturation ◽  
Intravenous Iron ◽  
Accurate Method ◽  
Separate Entity ◽  
Patients With Heart Failure

Abstract The 2016 ESC/HFA heart failure (HF) guidelines emphasize the importance of identifying and treating iron deficiency (ID) in patients with HF. Iron deficiency can occur in half or more of HF sufferers, depending on age and the phase of the disease. Iron deficiency can be a cause of anaemia, but it is also common even without anaemia, meaning that ID is a separate entity, which should be screened for within the HF population. Although assessment of iron stores in bone marrow samples is the most accurate method to investigate iron status, it is not practical in most HF patients. Levels of circulating iron biomarkers are an easily available alternative; especially, ferritin and transferrin saturation (Tsat). In patients with HF serum ferritin level &lt;100 µg/L (regardless of Tsat value) or between 100 and 299 µg/L with Tsat &lt;20% are considered as recommended criteria for the diagnosis of ID, criteria which have been used in the clinical trials in HF that have led to a recommendation to treat ID with intravenous iron. We discuss the optimal measures of iron biomarkers in patients with HF in order to screen and monitor iron status and introduce some novel ways to assess iron status.

Sign in / Sign up

Export Citation Format

Share Document