ESA guideline

BACKGROUND: Despite the widespread use of erythropoietin-stimulating agents (ESAs) to treat anemia in patients undergoing hemodialysis, the relative mortality risks associated with use of different types of ESAs are unknown. METHODS: To compare the mortality risk associated with use of short-acting ESAs versus long-acting ESAs, we conducted a nationwide cohort study of 194,698 hemodialysis patients in Japan who received either a short-acting (epoetin α / β or epoetin κ ) or a long-acting (darbepoetin or epoetin β pegol) ESA...

BACKGROUND: Anemia is a major comorbidity of patients with end-stage renal disease and poses an enormous economic burden to health-care systems. High dose erythropoiesis-stimulating agents (ESAs) have been associated with unfavorable clinical outcomes. We explored whether mixed-dilution hemodiafiltration (Mixed-HDF), based on its innovative substitution modality, may improve anemia outcomes compared to the traditional post-dilution hemodiafiltration (Post-HDF). METHODS: We included 174 adult prevalent dialysis patients (87 on Mixed-HDF, 87 on Post-HDF) treated in 24 NephroCare dialysis centers between January 2010 and August 2016 into this retrospective cohort study...

BACKGROUND: Anemia is extremely common among dialysis patients and underlies some of the symptoms associated with reduced kidney function, including fatigue, depression, reduced exercise tolerance, and dyspnea. OBJECTIVES: A clearer cognition of the prognosistic impact of hemoglobin (Hb) or hematocrit (Hct) target for the outcomes of dialysis patients is urgent. This article aims to establish the suitable hemoglobin in order to provide clinical guidance. METHODS: MEDLINE, EmBase, the Cochrane Library and other databases were searched with both MeSH terms and keywords to gather randomized controlled trials that assessed all-cause mortality, cardiovascular events, fistula thrombosis, infectious diseases and transfusion among dialysis-dependent patients using erythropoiesis-stimulating agents...

BACKGROUND: The optimal treatment algorithm for iron therapy and the use of erythropoiesis-stimulating agents (ESA) in anemic hemodialysis (HD) patients has not been established. Hemoglobin (Hb) target levels can be achieved through more frequent intravenous (IV) iron use with lower ESA dose, or with less iron dosing but higher ESA. ESA therapy to correct anemia may result in severe arterial and venous thrombotic complications and the evidence base evaluating hard clinical outcomes related to the use of IV iron is sparse...

Background: Vadadustat, an inhibitor of hypoxia-inducible factor prolyl-4-hydroxylase domain dioxygenases, is an oral investigational agent in development for the treatment of anemia secondary to chronic kidney disease. Methods: In this open-label Phase 2 trial, vadadustat was evaluated in 94 subjects receiving hemodialysis, previously maintained on epoetin alfa. Subjects were sequentially assigned to one of three vadadustat dose cohorts by starting dose: 300 mg once daily (QD), 450 mg QD or 450 mg thrice weekly (TIW)...

BACKGROUND: Regulation of body iron occurs at cellular, tissue, and systemic levels. In healthy individuals, iron absorption and losses are minimal, creating a virtually closed system. In the setting of chronic kidney disease and hemodialysis (HD), increased iron losses, reduced iron absorption, and limited iron availability lead to iron deficiency. Intravenous (IV) iron therapy is frequently prescribed to replace lost iron, but determining an individual's iron balance and stores can be challenging and imprecise, contributing to uncertainty about the long-term safety of IV iron therapy...

Background: Erythropoiesis-stimulating agents (ESAs) are widely used to treat anaemia in patients with chronic kidney disease. The issue of ESA safety has been raised in multiple studies, with correlates derived for elevated cancer incidence and mortality. Whether these associations are related to ESA dose or the typology of the patient remains obscure. Methods: A multicentre, observational retrospective propensity score-matched study was designed to analyse the effects of weekly ESA dose in 1679 incident haemodialysis (HD) patients...

Hyporesponsiveness to erythropoiesis-stimulating agent therapy in dialysis patients is poorly understood. Some studies report an improvement in the erythropoiesis-stimulating agent resistance index (ERI) with hemodiafiltration (HDF) versus high-flux hemodialysis (HD). We explored ERI dynamics in 38,340 incident HDF and HD patients treated in 22 countries over a 7-year period. Groups were matched by propensity score at baseline (6 months after dialysis initiation). The follow-up period (mean of 1.31 years) was stratified into 1 month intervals with delta analyses performed for key ERI-related parameters...

BACKGROUND: Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. STUDY DESIGN: Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. SETTING & PARTICIPANTS: Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa...

Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years...

Safety concerns with erythropoietin analogues and intravenous (IV) iron for treatment of anemia in CKD necessitate development of safer therapies. Roxadustat (FG-4592) is an orally bioavailable hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated erythropoiesis through HIF-mediated transcription. We performed an open-label, randomized hemoglobin (Hb) correction study in anemic (Hb≤10.0 g/dl) patients incident to hemodialysis (HD) or peritoneal dialysis (PD). Sixty patients received no iron, oral iron, or IV iron while treated with roxadustat for 12 weeks...

BACKGROUND: Iron deficiency anaemia is common in patients with chronic kidney disease, and intravenous iron is the preferred treatment for those on haemodialysis. The aim of this trial was to compare the efficacy and safety of iron isomaltoside 1000 (Monofer®) with iron sucrose (Venofer®) in haemodialysis patients. METHODS: This was an open-label, randomized, multicentre, non-inferiority trial conducted in 351 haemodialysis subjects randomized 2:1 to either iron isomaltoside 1000 (Group A) or iron sucrose (Group B)...

Optimal treatment algorithms for erythropoiesis-stimulating agent (ESA) and iron therapy in anemic CKD patients are lacking. Kuragano et al. evaluated hemodialysis patients over two years and report increased mortality risk and/or adverse events in those with high serum ferritin levels and high ferritin fluctuations, and an increase in adverse events in iron users. Clinical practice should avoid disproportionately high ESA or iron doses to achieve hemoglobin targets, particularly in those with significant comorbidity or ESA resistance...

This review aims to summarize the available evidence of the effectiveness of oral iron in patients receiving dialysis. Four small randomized controlled trials (105 evaluated patients) compared oral iron supplements with placebo or no treatment; hemoglobin and ferritin levels did not differ significantly between groups at the end of the studies, while transferrin saturation levels fell in the placebo group in two studies. One trial (46 evaluated patients), comparing different ferrous iron preparations, found that hemoglobin levels and iron indices were maintained, but not increased...

Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group has produced comprehensive clinical practice guidelines for the management of anaemia in CKD patients. These guidelines addressed all of the important points related to anaemia management in CKD patients, including therapy with erythropoieis stimulating agents (ESA), iron therapy, ESA resistance and blood transfusion use. Because most guidelines were 'soft' rather than 'strong', and because global guidelines need to be adapted and implemented into the regional context where they are used, on behalf of the European Renal Best Practice Advisory Board some of its members, and other external experts in this field, who were not participants in the KDIGO guidelines group, were invited to participate in this anaemia working group to examine and comment on the KDIGO documents in this position paper...