Use Of Erythropoiesis-stimulating Agents Research Articles

Total iron binding capacity is a predictor for muscle loss in maintenance hemodialysis patients.

Protein-energy wasting in hemodialysis (HD) patients is characterized by decreased skeletal muscle mass and plasma protein. Some previous studies reported relationships between skeletal muscle dysfunction and iron deficiency. Dialysis patients with malnutrition may have a functional iron deficiency (FID) because of inflammation. Serum total iron binding capacity (TIBC), correlated with transferrin, is a nutritional status marker in HD patients and a biomarker of iron status. The relationship between muscle loss and iron status is unknown. The aim of the present study was to assess the relationship between iron status and change in skeletal muscle mass. A prospective cohort of 267 HD patients was examined for 12months. Blood samples were obtained at baseline to measure TIBC, ferritin, transferrin saturation (TSAT), and hepcidin-25. Nutritional status and changes in muscle mass were assessed by subjective global assessment, albumin, creatinine index, and percentage creatinine generation rate. At baseline, lower tertiles of TIBC were significantly related to lower muscle mass and albumin levels; they were also significantly correlated with high ferritin, hepcidin-25, and TSAT levels, as well as a higher proportion of use of erythropoiesis-stimulating agents. Multiple regression analysis adjusted with confounders showed TIBC was an independent biomarker for decreased muscle mass and albumin. Change in muscle mass remained significantly decreased in the lower tertile of TIBC and in malnourished patients. The present study demonstrated relationships between FID and muscle loss. TIBC was an independent biomarker of muscle loss in HD patients, considering iron status, inflammation, oxidative stress, and malnutrition.

Association of anemia and iron parameters with mortality among prevalent peritoneal dialysis patients in Taiwan: the AIM-PD study

In 1996, the National Health Insurance Administration of Taiwan applied a restrictive reimbursement criteria for erythropoiesis-stimulating agents (ESAs) use in patients with chronic kidney disease. The maximal ESAs dosage allowed by insurance is capped at 20,000 U of epoetin per month. Nephrologists avoided the use of high ESA dosages to achieve a hemoglobin level of 10–11 g/dL using iron supplementation. We assessed the association of anemia and iron parameters with mortality among peritoneal dialysis (AIM-PD) patients. A retrospective cohort study was conducted based on the Taiwan Renal Registry Data System. From January 1, 2000 to December 31, 2008, we enrolled 4356 well-nourished PD patients who were older than 20 years and had been receiving PD for more than 12 months. All patients were divided into subgroups according to different hemoglobin, ferritin and transferrin saturation (TSAT) values. Patients were followed until death or December 31, 2008. In a median 2.9-year study period, 694 (15.9%) patients died. By multivariate adjustment, a hemoglobin level lower than 10 g/dL was significantly associated with a higher risk for all-cause and cardiovascular deaths. Moreover, a serum ferritin level higher than 800 ng/mL was associated with a higher risk for all-cause deaths, and a TSAT value between 20 and 50% was associated with the lowest all-cause mortality. In conclusions, we recommend avoiding a low hemoglobin level and a serum ferritin level of more than 800 ng/mL and maintaining a TSAT value between 20 and 50%, as these conditions were associated with lower risks of all-cause mortality in the AIM-PD study.

New-onset anemia and associated risk of ESKD and death in non-dialysis CKD patients: a multicohort observational study.

ABSTRACTBackgroundAnemia is a common complication of chronic kidney disease (CKD), but its incidence in nephrology settings is poorly investigated. Similarly, the risks of adverse outcomes associated with new-onset anemia are not known.MethodsWe performed a pooled analysis of three observational cohort studies including 1031 non-anemic CKD patients with eGFR <60 mL/min/1.73 m2 regularly followed in renal clinics. We estimated the incidence of mild anemia (hemoglobin 11–12 g/dL in women and 11–13 g/dL in men) and severe anemia (hemoglobin <11 g/dL or use of erythropoiesis-stimulating agents) during a 3-year follow-up period. Thereafter we estimated the risk of end-stage kidney disease (ESKD) and all-cause death associated with new-onset mild and severe anemia.ResultsThe mean age was 63 ± 14 years, 60% were men and 20% had diabetes. The mean estimated glomerular filtration rate (eGFR) was 37 ± 13 mL/min/1.73 m2 and the median proteinuria was 0.4 g/day [interquartile range (IQR) 0.1–1.1]. The incidence of mild and severe anemia was 13.7/100 patients-year and 6.2/100 patients-year, respectively. Basal predictors of either mild or severe anemia were diabetes, lower hemoglobin, higher serum phosphate, eGFR <30 mL/min/1.73 m2 and proteinuria >0.50 g/day. Male sex, moderate CKD (eGFR 30–44 mL/min/1.73 m2) and moderate proteinuria (0.15–0.50 g/day) predicted only mild anemia. The incidence of anemia increased progressively with CKD stages (from 8.77 to 76.59/100 patients-year) and the proteinuria category (from 13.99 to 25.02/100 patients-year). During a median follow-up of 3.1 years, 232 patients reached ESKD and 135 died. Compared with non-anemic patients, mild anemia was associated with a higher adjusted risk of ESKD {hazard ratio [HR] 1.42 [95% confidence interval (CI) 1.02–1.98]} and all-cause death [HR 1.55 (95% CI 1.04–2.32)]. Severe anemia was associated with an even higher risk of ESKD [HR 1.73 (95% CI 1.20–2.51)] and death [HR 1.83 (95% CI 1.05–3.19)].ConclusionsNew-onset anemia is frequent, particularly in patients with more severe renal damage and in those with diabetes mellitus. The occurrence of anemia, even of a mild degree, is associated with mortality risk and faster progression towards ESKD.

Updated recommendations on the use of ruxolitinib for the treatment of myelofibrosis

ABSTRACT Objectives Myelofibrosis is a rare bone marrow disorder associated with a high symptom burden, poor prognosis, and shortened survival. While allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for myelofibrosis, the only approved and reimbursed pharmacotherapy for non-HSCT candidates in Belgium is ruxolitinib. Methods These updated recommendations are based on a consensus reached during two meetings and provide guidance for ruxolitinib administration in myelofibrosis patients considering the particularities of Belgian reimbursement criteria. Results and Discussion In Belgium, ruxolitinib is indicated and reimbursed for transplant-ineligible myelofibrosis patients from intermediate-2- and high-risk groups and from the intermediate-1-risk group with splenomegaly. Our recommendation is to also make ruxolitinib available in the pre-transplant setting for myelofibrosis patients with splenomegaly or heavy symptom burden. Before ruxolitinib initiation, complete blood cell counts are recommended, and the decision on the optimal dosage should be based on platelet count and clinical parameters. In anemic patients, we recommend starting doses of ruxolitinib of 10 mg twice daily for 12 weeks and we propose the use of erythropoiesis-stimulating agents in patients with endogenous erythropoietin levels ≤500 mU/mL. Increased vigilance for opportunistic infections and second primary malignancies is needed in ruxolitinib-treated myelofibrosis patients. Ruxolitinib treatment should be continued as long as there is clinical benefit (reduced splenomegaly or symptoms), and we recommend progressive dose tapering when stopping ruxolitinib. Conclusion Based on new data and clinical experience, the panel of experts discussed ruxolitinib treatment in Belgian myelofibrosis patients with a focus on dose optimization/monitoring, adverse events, and interruption/rechallenge management.

Preoperative Hemoglobin Optimization in Jehovah's Witness Cardiovascular Surgery Patients with Anemia and Barriers to Care

Cardiac surgery has a risk for extensive blood loss which poses a particular challenge in individuals refusing blood transfusions. Additionally, preoperative anemia with a hemoglobin (Hb) below 13 g/dL in men and 12 g/dL in women is associated with increased short and long-term complications and mortality and increases the need for blood transfusion support. The current guidelines for perioperative anemia management recommend optimizing hemoglobin levels prior to surgery and utilizing blood conservation techniques during the procedure. At present red blood cell (RBC) transfusions during cardiac surgery are usually recommended when Hb levels are below 7-8 g/dL a restrictive transfusion strategy to reduce complications. However, the use of any RBC transfusions is associated with worse outcomes in cardiac surgery compared with those who do not receive transfusions.We have found that JW seek out quality health care and accept the vast majority of medical treatments once they are educated. The Transfusion Free Medicine Coordinator's role in the Anemia Clinic is to endorse clinical strategies for managing hemorrhage and anemia without blood transfusion. They educate and counsel the patients so they can decide as to what blood fractions and cell salvage techniques they will accept. We have found that some Health Care Providers are unaware that ESAs also contain albumin so JW patients may be given this product without that knowledge. The vast majority of patients will accept the use of ESAs but find the cost prohibitive.Jehovah's Witness patients have provided a natural case study for examining how well adjuvant therapies can improve preoperative anemia without transfusions and continue with good outcomes. Hb optimization is achieved through the use of intravenous iron and, if needed, erythropoiesis stimulating agents (ESAs). In Table 1 we highlight our single center data in which all cardiovascular surgeries were performed by a surgeon experienced in blood-conservation strategies. Our thirty-day re-admission rates for all patients was zero percent, compared to state-specific data, which estimates about an 11.7% rate of re-admission. The data illustrate the need to have a target Hb 13 or above to allow for the decline that may occur during the hospital stay. Of note no thromboembolic events have occurred with the use of an ESA in this group.Although ESAs are approved to optimize Hb in orthopedic surgery, they are not covered for cardiac surgery which has presented a significant challenge to patients who can not safely proceed to surgery until a target Hb between 13 to 15 g/dL is achieved.These data highlight the utility and safety associated with the use of ESAs for patients who do not accept blood products at an experienced Center for Transfusion-Free Medicine, such as ours. At this time, since insurance companies do not cover the cost of ESAs for patients needing life-saving cardiovascular operations, cost is a prohibitive barrier for patients. Unfortunately, it is not uncommon for patients to have to borrow money from others or set up payment plans. We hope that analyses like ours will help drive changes in reimbursement policies, particularly for patients who based on religious convictions, cannot receive blood products, and thus for whom pre-operative hemoglobin optimization is of utmost importance. [Display omitted] DisclosuresNo relevant conflicts of interest to declare. OffLabel Disclosure:Erythropoiesis-stimulating agent (ESA) are indicated for the treatment of anemia due to Chronic Kidney Disease in patients on dialysis and not on dialysis, Zidovudine in patients with HIV-infection, anemia due to myelosuppressive chemotherapy and reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery

Lower-Risk Myelodysplastic Syndromes: Erythropoiesis-Stimulating Agent Treatment Approaches and Outcomes in the United States

Lower-Risk Myelodysplastic Syndromes: Erythropoiesis-Stimulating Agent Treatment Approaches and Outcomes in the United States

A Phase 2a Study Evaluating the Safety and Pharmacokinetics (PK) of Luspatercept in Pediatric Patients with Transfusion-Dependent β-Thalassemia (TDT)

A Phase 2a Study Evaluating the Safety and Pharmacokinetics (PK) of Luspatercept in Pediatric Patients with Transfusion-Dependent β-Thalassemia (TDT)

Biomarkers of Uremic Cardiotoxicity.

Cardiovascular (CV) morbidity and mortality increase along with the progression of chronic kidney disease (CKD). The potential novel biomarkers of cardiotoxicity have been tested with the aim of the early detection of patients at high CV risk, and among them are markers of inflammation, oxidative stress, acute renal injury, and microRNAs. The study analyzed biomarkers in non-dialysis-dependent (NDD; stage 3a–4 CKD) and dialysis-dependent (DD) CKD patients. The prospective cohort study included 87 patients who were followed for 18 months, during which period newly occurred CV events were recorded. Cox regression analysis confirmed serum albumin, urea, interventricular septum thickness diameter (IVST), the use of calcium antagonist, and erythropoiesis-stimulating agent to be significant predictors of CV outcome. No significant difference was observed in biomarkers of inflammation, oxidative stress, acute kidney injury (IL-18, CRP, ferritin, IMA, SOD, NGAL, and KIM-1), and miR-133a, in regards to the presence/absence of CV event, CV death, and left ventricular hypertrophy. Serum albumin, urea, IVST, and the use of calcium antagonist and erythropoiesis-stimulating agents were confirmed to be factors associated with CV events in CKD patients. Apart from traditional risk factors, new research is needed to define novel and reliable biomarkers of cardiotoxicity in CKD patients.

Efficacy and Cardiovascular Adverse Effects of Erythropoiesis Stimulating Agents in the Treatment of Cancer-Related Anemia: A Systematic Review of Randomized Controlled Trials.

Anemia is a common complication of cancer. Treatment of anemia in cancer is crucial as anemia adversely affects the quality of life, therapeutic outcomes, and overall survival. Erythropoiesis stimulating agents (ESAs) are valuable drugs for treating cancer-related anemia. Cardiovascular adverse effects are a significant concern with ESA therapy, and there is wide variability in therapeutic goals and characteristics of patients who undergo treatment with ESAs. As a result, a careful analysis of the currently available data on the efficacy and safety of these drugs is necessary. This data analysis will aid in the rational use of ESAs for the treatment of anemia in cancer. The objective of this systematic review is to elucidate the pathogenesis of anemia in cancer, assess the effectiveness of ESAs in treating anemia in cancer, and the overall risk of cardiovascular adverse effects associated with the use of ESAs and their impact on prognosis.We searched literature from online databases - PubMed, PubMed Central, MEDLINE, Cochrane Library, and clinical trials register (clinicaltrials.gov) to identify prospective phase II and phase III randomized controlled trials (RCTs). We chose RCTs that directly compared patients with cancer who were treated with ESAs to those who were not treated with ESAs. January 2008 was taken as the lower date limit and May 2021 as the upper date limit. Only English language literature and human studies were included. The quality appraisal was completed using the Cochrane risk bias assessment tool, and data from a total of 10,738 patients with cancer in 17 RCTs were identified and included for systematic review.Our review concludes that ESAs effectively reduce the necessity for blood transfusions and increase mean hemoglobin levels in anemic cancer patients. ESA therapy is associated with cardiovascular adverse effects, including venous thromboembolism, thrombophlebitis, hypertension, ischemic heart disease, cardiac failure, arrhythmia, arterial thromboembolism, and cardiac arrest. Aggressive ESA dosing to achieve higher hemoglobin levels and preexisting uncontrolled hypertension increases these cardiovascular side effects. Venous thromboembolism is the most significant adverse effect attributed to ESA therapy. However, there is no major change in overall survival with ESA therapy, and administration of ESAs can be carried out in anemic cancer patients with careful assessment of thromboembolism risk factors, risk-benefit ratio, and monitoring of hemoglobin levels.

Factors Associated With Advanced Colorectal Neoplasia in Patients With CKD

The risk of developing colorectal cancer in patients with chronic kidney disease (CKD) is twice that of the general population, but the factors associated with colorectal cancer are poorly understood. The aim of this study was to identify factors associated with advanced colorectal neoplasia in patients with CKD. Prospective cohort study. Patients with CKD stages 3-5, including those treated with maintenance dialysis or transplantation across 11 sites in Australia, New Zealand, Canada, and Spain, were screened for colorectal neoplasia using a fecal immunochemical test (FIT) as part of the Detecting Bowel Cancer in CKD (DETECT) Study. Baseline characteristics for patients at the time of study enrollment were ascertained, including duration of CKD, comorbidities, and medications. Advanced colorectal neoplasia was identified through a 2-step verification process with colonoscopy following positive FIT and 2-year clinical follow-up for all patients. Potential factors associated with advanced colorectal neoplasia were explored using multivariable logistic regression. Sensitivity analyses were performed using grouped LASSO (least absolute shrinkage and selection operator) logistic regression. Among 1,706 patients who received FIT-based screening-791 with CKD stages 3-5 not receiving kidney replacement therapy (KRT), 418 receiving dialysis, and 497 patients with a functioning kidney transplant-117 patients (6.9%) were detected to have advanced colorectal neoplasia (54 with CKD stages 3-5 without KRT, 34 receiving dialysis, and 29 transplant recipients), including 9 colorectal cancers. The factors found to be associated with advanced colorectal neoplasia included older age (OR per year older, 1.05 [95% CI, 1.03-1.07], P<0.001), male sex (OR, 2.27 [95% CI, 1.45-3.54], P<0.001), azathioprine use (OR, 2.99 [95% CI, 1.40-6.37], P=0.005), and erythropoiesis-stimulating agent use (OR, 1.92 [95% CI, 1.22-3.03], P=0.005). Grouped LASSO logistic regression revealed similar associations between these factors and advanced colorectal neoplasia. Unmeasured confounding factors. Older age, male sex, erythropoiesis-stimulating agents, and azathioprine were found to be significantly associated with advanced colorectal neoplasia in patients with CKD.

Anemia in Cardiovascular Disease: Marker of Disease Severity or Disease-modifying Therapeutic Target?

In this review paper, we examine the latest evidence regarding the use of iron supplementation, erythropoiesis-stimulating agents (ESAs), and blood transfusions as therapeutic targets for anemia to mitigate morbidity and mortality in patients with cardiovascular disease. Intravenous ferric carboxymaltose (FC) injections in heart failure (HF) have resulted in improved self-reported patient symptoms; higher exercise capacity, as measured by 6-min walk test distance in anemic patients; and lower re-hospitalization rates in iron deficient patients. Darbepoetin alfa has shown evidence of improved Kansas City Cardiomyopathy Questionnaire scores. No mortality benefits have been noted thus far with FC injections or darbepoetin in HF, with an increase in adverse events with darbepoetin. Aggressive transfusions (Hg < 10g/dL) are not associated with improved outcomes in cardiovascular disease. Quality of life metrics, rather than mortality, appear to improve with IV FC and ESA use in HF. More studies are required to see if these treatments have a role in coronary artery disease. Current evidence suggests that anemia is a marker of underlying disease severity, with a limited role in disease modification. Further studies are required to solidify our understanding of this topic.

Prolonged Intradialytic Hypoxemia Is Associated With Functional Disturbances in Erythrocytes

Prolonged Intradialytic Hypoxemia Is Associated With Functional Disturbances in Erythrocytes

Phase 3 Randomized Study Comparing Vadadustat with Darbepoetin Alfa for Anemia in Japanese Patients with Nondialysis-Dependent CKD

Standard care for treating anemia in patients with CKD includes use of erythropoiesis-stimulating agents, which sometimes involves increased risks of cardiovascular morbidity and mortality. Previous studies in patients with anemia and nondialysis-dependent CKD (NDD-CKD) found significantly elevated hemoglobin levels with use of vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, compared with placebo. In this phase 3, open-label, active-controlled noninferiority trial, we randomized 304 Japanese adults with anemia in NDD-CKD (including erythropoiesis-stimulating agent users and nonusers) to oral vadadustat or subcutaneous darbepoetin alfa for 52 weeks. The primary efficacy end point was average hemoglobin at weeks 20 and 24. Safety data included adverse events (AEs) and serious AEs. A total of 151 participants received vadadustat and 153 received darbepoetin alfa. Least squares mean of the average hemoglobin at weeks 20 and 24 was 11.66 (95% confidence interval [95% CI], 11.49 to 11.84) g/dl for vadadustat and 11.93 (95% CI, 11.76 to 12.10) g/dl for darbepoetin alfa. The 95% CIs for both treatments were within the target hemoglobin range (11.0-13.0 g/dl), and the lower 95% confidence limit for the difference between groups (-0.50 g/dl) was above the predefined noninferiority margin (-0.75 g/dl), demonstrating noninferiority of vadadustat to darbepoetin alfa. Similar proportions of patients in each group reported AEs and serious AEs. The most frequent AEs with vadadustat were nasopharyngitis, diarrhea, and constipation. In Japanese patients with NDD-CKD, vadadustat was noninferior to darbepoetin alfa, was effective up to week 52 in terms of average hemoglobin, and was generally well tolerated. These results suggest that vadadustat may be a potential treatment for anemia in this patient population.

Expanded hemodialysis as effective alternative to on-line hemodiafiltration: A randomized mid-term clinical trial.

Expanded hemodialysis (HDx), using medium cut‐off membrane, is a novel therapy that effectively clears middle molecules (MMs). We aimed to compare HDx to hemodiafiltration (HDF) in an open randomized clinical study. Patients currently on HDF (age 18–80 years; on HDF >3 months) were randomized to switch to HDx (N = 21) or continue HDF (N = 22) with a 24‐week follow‐up. Pre‐ to post‐dialysis reduction ratios (RR) and changes in pre‐dialysis levels over time were evaluated for MMs and clinical biomarkers. Use of erythropoiesis‐stimulating agents (ESAs) was assessed. HDx showed greater RR for YKL‐40 while RR appeared similar between groups for beta2‐microglobulin, FGF‐23, and free light chains. Intradialytic changes in inflammatory biomarkers (IL‐6, CRP, PTX3) did not differ between therapies. Changes from baseline to 12 and 24 weeks did not differ between groups for MMs, inflammatory markers, albumin, fibrinogen, hemoglobin, PTH, and phosphorus. Use of ESAs tended to decrease in HDx arm while remaining stable in HDF arm. HDx appeared safe with similar clinical effectiveness as HDF. With fewer requirements and resource needs, HDx provides an attractive alternative to HDF.

The Effect of Erythropoiesis-Stimulating Agent on the Management of Chemotherapy-Induced Anemia and Tumor Growth in Diffuse Large B-Cell Lymphoma Patients

Bacground : Erythropoiesis stimulating agents (ESA) increase hemoglobin levels, reduce red blood cell (RBC) transfusion requirements and improve the quality of life (QoL) in patients with chemotherapy-associated anemia (CAA). The purpose of this study is to investigate the efficacy and safety of ESA for management of anemia caused by chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL). And this study estimated quality of life as measured by Functional Assessment of Cancer Therapy Scales for anemia (FACT-An) additionally. Until now, several studies suggested that ESA can affect the progression of tumors. This study conducted experiments to confirm whether the results of previous studies were also applied to lymphoma cells.Patients and Methods : This prospective, multicenter, phase II study enrolled 50 Histologically confirmed DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristin, and prednisolone (R-CHOP) chemotherapy. This study enrolled patients who were shown hemoglobin < 10.0 g/dL at least 3 cycles after starting R-CHOP, were planning to receive at least 4 times of darbepoetin, could read Quality of life as measured by FACT-An and agreed with informed consent. However, this study excluded patients who combined iron deficiency anemia, received erythropoietin at least one months before starting darbepoetin, serious pre-existing medical condition, and untreated primary or metastatic CNS(central nervous system) malignancy. This study was registered in clinicaltrial.gov, and more information can be found at NCT02890602. All patients received darbepoietin alfa at fixed dose of 360 mg once every 3 weeks and if the hemoglobin level exceeds 12 g/dL, administration of darbepoietin was stopped temporarily. In addition, DLBCL cell lines or primary DLBCL cells were tested in vitro to investigate if there were any adverse effects of ESAs on the cancer cell growth.Results : Fifty patients were enrolled between Sep 2012 and Oct 2016. The median age was 64.5 years (range: 34-79 years). The baseline clinical features were as follows: female sex, 68.0%; ECOG >1, 75.5%; stage III/IV, 80.0% and International Prognostic Index score (IPI) > 2, 53.3%, and mean serum ferritin level, 648.13±982.52. The baseline mean hemoglobin level was 9.24 g/dL and overall mean change in hemoglobin level was 1.54±1.3 g/dL at 16 weeks. 46% of total enrolled patients achieved an increase in Hb levels of at least 2 g/dL after 16 weeks of darbepoietin administration and median time to response was 8 weeks. The change of OoL was not significant from baseline to finish of ESA. Most adverse events were hematologic complications which were attributed to the primary disease or received chemotherapy. Only one patient had a thrombotic event which was Common Terminology Criteria for Adverse Events (CTCAE) grade I. Transfusion necessity was determined by clinical judgment and the transfusion rates were 18%. In in vitro study using DLBCL cells, erythropoietin or darbepoietin did not alter cancer cell viability nor rituximab-mediated cytotoxicity under the conditions we have tested.Conclusions : Our study has demonstrated that ESA is effective and safe for patients suffering from anemia after RCHOP chemotherapy. The use of ESA in patients with DLBCL did not deteriorate the quality of life of the patients during chemotherapy. Finally, our research have also shown that the use of ESA does not affect the growth of lymphoma cells. (EPOMA ClinicalTrials.gov number, NCT02890602) DisclosuresNo relevant conflicts of interest to declare.

An Integrated Analysis of Darbepoetin Alfa (DAR) in the Treatment of Anemia in Patients with Low- or Intermediate-1 (int-1) Risk Myelodysplastic Syndrome (MDS)

An Integrated Analysis of Darbepoetin Alfa (DAR) in the Treatment of Anemia in Patients with Low- or Intermediate-1 (int-1) Risk Myelodysplastic Syndrome (MDS)

Examining the Role of Novel CKD Therapies for the ADPKD Patient.

Two new classes of drugs, sodium-glucose cotransporter-2 inhibitors (SGLT2is) and hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (HIF-PHis), are likely to have a significant effect on the management of CKD. SGLT2is were approved by the Food and Drug Administration for the treatment of diabetes in 2013, and have now been shown to slow the progressive loss of kidney function in both diabetic and nondiabetic kidney disease (1⇓–3). SGLT2is demonstrate mortality benefit for patients with CKD, distinguishing them from renin-angiotensin-aldosterone system inhibitors (RAASis), which have otherwise been the mainstay of treatment for patients with diabetic or proteinuric CKD and which provide mortality benefit for a subset of patients with heart failure with reduced ejection fraction (4). Studies of SGLT2is in nondiabetic CKD have been extremely encouraging and we expect that these medications will soon become standard of care for diabetic or nondiabetic, and proteinuric or nonproteinuric, CKD. The potential benefits of SGLT2is have not been specifically explored in autosomal dominant polycystic kidney disease (ADPKD), because both major trials of SGLT2is in nondiabetic CKD (the ongoing EMPA-KIDNEY study [5] and the recently published DAPA-CKD study [1]) excluded patients with ADPKD. Separately, HIF-PHis are anticipated to have a major effect in the management of anemia of CKD. The current use of erythropoiesis-stimulating agents (ESAs) involves a complex balance between treating anemia and limiting potential adverse effects of cardiovascular events, hypertension, and loss of vascular access (6). HIF-PHis have beneficial effects on iron metabolism, hypertension, and inflammation (7). However, there are concerns that HIF activation could promote cyst growth (8) when used for treatment of patients with ADPKD. Here, we examine reasons why patients with ADPKD, who comprise approximately 5% of the ESKD population in the United States, warrant unique consideration regarding treatment with SGLT2is or HIF-PHis. We …

476-P: Multidisciplinary Predialysis Team Education for Patients with Diabetic Nephropathy, Postponed Hemodialysis Induction, and Prolonged Survival after Hemodialysis Induction

To determine whether a multidisciplinary team approach (MTA) improves the course of hemodialysis (HD), including clinical status, hospital admission costs, and prognosis after HD induction, in patients with diabetic nephropathy (DN), we compared the HD course of 36 patients who received MTA and 33 patients managed with a dietitian approach (DA) (n=69; 47 men: mean age, 59±12 years; 66 type 2 diabetic patients). HD started between January 2010 and June 2016. The observation period ended with death or in September 2018. MTA staff consisted of physicians, dietitians, nurses, laboratory technologists, and pharmacists. They provided broad education, including advice on nutrition, medication, medical examinations, and foot care. There were no significant differences in HbA1c, age, BMI, or eGFR between the groups when the baseline serum creatinine (S-Cr) was 2.0 mg/dL. There were no differences in the incidence of severe hypoglycemia or use of erythropoiesis-stimulating agents or RAS inhibitors. The MTA group was more likely to undergo 24-h urine collection than the DA group (likelihood ratio, 6.11; p=0.014). The MTA group had smaller CTR than the DA group (52.0% vs. 55.8%; p=0.024). Sodium intake based on 24-h urine collection was correlated with CTR (p=0.033). The MTA group had lower cost per admission for HD induction than the DA group ($20,580±14,170 vs. $14,804±8,397; p=0.023). Kaplan-Meier survival analysis showed that the MTA group had a longer duration from Cr 2.0 mg/dL to HD initiation (Wilcoxon 5.679; p=0.017) and from HD initiation to death than the DA group (Wilcoxon 3.860; p=0.050). MTA provided multiple broad effects with a longer duration before HD initiation, better clinical course, lower costs, and prolonged survival after HD induction compared with DA when observation started at the same S-Cr level. Future studies are needed to examine whether MTA has legacy effects after HD initiation. Disclosure M. Hitomi: None. T. Sato: None. T. Moriya: None.

Ferric carboxymaltose vs. ferrous sulfate for the treatment of anemia in advanced chronic kidney disease: an observational retrospective study and cost analysis

In non-dialysis-dependent chronic kidney disease (NDD-CKD), erythropoiesis-stimulating agents (ESAs) and iron supplementation are essential for anemia management. Ferric carboxymaltose (FCM) is a relatively novel intravenous iron formulation used in different clinical settings, although scarce data exist in NDD-CKD patients. Primary objective of this study was to retrospectively evaluate the efficacy of FCM compared with oral ferrous sulfate for the treatment of iron-deficiency anemia in a cohort of NDD-CKD patients, considering also the treatment costs. This was a monocentric, retrospective observational study reviewing 349 NDD-CKD patients attending an outpatient clinic between June 2013 and December 2016. Patients were treated by either FCM intravenous infusion or oral ferrous sulfate. We collected serum values of hemoglobin, ferritin and transferrin saturation (TSAT) and ESAs doses at 12 and 18 months. The costs related to both treatments were also analysed. 239 patients were treated with FCM intravenous infusion and 110 patients with oral ferrous sulfate. The two groups were not statistically different for age, BMI and eGFR values. At 18 months, hemoglobin, serum ferritin and TSAT values increased significantly from baseline in the FCM group, compared with the ferrous sulfate group. ESAs dose and rate of infusion decreased only in the FCM group. At 18 months, the treatment costs, analysed per week, was higher in the ferrous sulfate group, compared with the FCM group, and this was mostly due to a reduction in ESAs prescription in the FCM group. Routine intravenous FCM treatment in an outpatient clinic of NDD-CKD patients results in better correction of iron-deficiency anemia when compared to ferrous sulfate. In addition to this, treating NDD-CKD patients with FCM leads to a significant reduction of the treatment costs by reducing ESAs use.

ERYTHROFERRONE AS A NEW BIOMARKER ASSOCIATED WITH ANEMIA IN IRAQI PATIENTS WITH CKD

Background: Erythroferrone (ERFE) is a glycoprotein hormone synthesis and release by erythroblasts. Recently identified as an erythropoietic regulator and activated in response to stimulating erythropoietin (Epo). In chronic kidney diseases (CKD), anemia is a hallmark disorder due to a decrease in hyposensitive erythropoietic to the Epo; these patients recommended to use of Erythropoiesis-stimulating agents (ESAs). The aim: This study aimed to assess serum ERFE level in patients with CKD and investigate the continuing effects of long-term anemic ESA use associated with markers of erythropoiesis and iron metabolism. Methods: Sixty-five CKD patients divided in two groups, included 30 hemodialyses (HD) and 35 without hemodialysis (non-HD) CKD patients, were compared to 25 healthy voluntaries matched by gender and age enrolled in the current study. Serum ERFE level was measured by an enzyme-linked immunosorbent assay (ELISA). Results: Serum ERFE level was significantly elevated in HD patients median (IQR) about 17.25 (13.4) ng/mL, odds ratio (OR = 10.161), (AUC 0.996) greater than CKD 4(6.1) ng/ml, (OR = 6.295), (AUC = 0.984) p 0.001; also, these are positively correlated with the use of ESA in HD, and CKD (r = 1.00 and r = 0.95) respectively as compared to healthy group 2(2.1) ng/ml. Serum ERFE levels were significantly negative (p 0.05) in both CKD and HD patients related to GFR (r = -0.396, and r = -0.68), transferrin saturation (TS%) (r = -0.842, and r = -0.877), serum levels of Ferritin (r = -0.865 and r = -0.866), and Iron (r = -0.860, and r = -0.851), RBC (r = -0.841, and r = -0.843), hemoglobin (Hb) (r = -0.758, and r = -0.796). Conclusion: The present study demonstrated that elevated serum ERFE levels associated with erythropoietic activity and anemia are higher in CKD with HD and non -HD patients treated with ESA than in non-ESA patients. This study suggested using ERFE as a successful tool for erythropoietic activity inspection in CKD, especially those taking ESAs to treat anemia.