Roxadustat

Roxadustat is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase, which increases endogenous erythropoiesis. WADA has included roxadustat and other HIF stabilizers on its list of prohibited substances. We describe here the case of an elite athlete (female, 31 years old, 168 cm and 53 kg) with an adverse analytical finding (AAF) with concentration of roxadustat in her urine at 0.289 ng/mL in the A sample and 0.529 ng/mL in the B sample (83% higher than A). A stability study was carried out, showing total stability of roxadustat at this concentration in urine exposed to light for 50 h, so photoisomerization degradation cannot explain the difference in concentration...

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) have played an important role in the treatment of renal anemia in children, but cannot improve hemoglobin to target level in some cases. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, can stimulate endogenous erythropoietin production and regulate iron metabolism even in patients with kidney failure. However, roxadustat has not yet been approved for use in children. CASE-DIAGNOSIS/TREATMENT: We report a case of refractory renal anemia in an 80-day-old boy, who was hyporesponsive to ESAs even in combination with iron supplementation and transfusion...

Patients undergoing hemodialysis often require zinc supplementation owing to hypozincemia, which may reduce serum copper concentrations. However, hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs), which are used to treat renal anemia, have been reported to increase serum copper. Therefore, this study investigates the effectiveness of a combination of HIF-PHIs and zinc for the stabilization of serum copper and zinc concentrations during zinc supplementation for patients undergoing hemodialysis with renal anemia and hypozincemia...

Hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs) are a novel group of drugs used to treat renal anemia, but their benefits vary among different trials. Our meta-analysis aims to assess the safety and efficacy of HIF-PHI versus erythropoiesis-stimulating agents (ESA) in managing anemia among patients with chronic kidney disease (CKD), regardless of their dialysis status. PubMed, Embase, and Google Scholar were queried to discover eligible randomized controlled trials (RCTs). To quantify the specific effects of HIF-PHI, we estimated pooled mean differences (MDs) and relative risks (RR) with 95% CIs...

OBJECTIVE: Although hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors have been developed for the treatment of renal anemia, their effects on cardiac and renal dysfunction remain unknown. We previously reported on Dahl salt-sensitive rats, in a rat model of salt-sensitive hypertension, that exhibited anemia and impaired expression of duodenal iron transporters after the development of hypertensive cardiac and renal dysfunction. Therefore, we investigated the effects of Roxadustat (FG-4592), an HIF-PH inhibitor, on anemia, iron regulation, and cardiac and renal dysfunction in Dahl salt-sensitive rats...

The link between chronic renal failure and anemia has been known for more than 180 years, negatively impacting the quality of life, cardiovascular risk, mortality, and morbidity of patients with chronic kidney disease (CKD). Traditionally, the management of anemia in CKD has been based on the use of replacement martial therapy, vitamin therapy, and the use of erythropoiesis-stimulating agents (ESAs). In recent years, alongside these consolidated therapies, new molecules known as hypoxia-induced factor prolyl-hydroxylase inhibitors (HIF-PHIs) have appeared...

Ocular hypertension during glaucoma can lead to hypoxia, activation of the HIF transcription factors, and a metabolic shift toward glycolysis. This study aims to test whether chronic HIF activation and the attendant metabolic reprogramming can initiate glaucoma-associated pathology independently of ocular hypertension. HIF-1α stabilization was induced in mice for 2 and 4 weeks by inhibiting prolyl hydroxylases using the small molecule Roxadustat. HIF-1α stabilization and the expression of its downstream bioenergetic targets were investigated in the retina by immunofluorescence, capillary electrophoresis, and biochemical enzyme activity assays...

The contributions of hypoxia and oxidative stress to the pathophysiology of acute ischemic stroke are well established and can lead to disruptions in synaptic signaling. Hypoxia and oxidative stress lead to the neurotoxic overproduction of reactive oxygen species (ROS) and the stabilization of hypoxia inducible factors (HIF). Compounds such as prolyl-4-hydroxylase domain enzyme inhibitors (PHDIs) have been shown to have a preconditioning and neuroprotective effect against ischemic insults such as hypoxia, anoxia, oxygen glucose deprivation (OGD) or H2 O2 ...

OBJECTIVE: To investigate the efficacy of roxadustat in hemodialysis patients with erythropoietin (EPO) hypo-responsive anemia. MATERIALS AND METHODS: This retrospective study included 55 hemodialysis patients with erythropoietin hypo-responsive anemia at the First Affiliated Hospital of Chongqing Medical University from January to December 2020. We observed their hemoglobin (Hb) changes, inflammatory factors, and adverse reactions before and after 12 weeks of roxadustat treatment...

BACKGROUND: Roxadustat is an oral hypoxia inducing factor-prolyl hydroxylase inhibitor (HIF-PHI) that regulates iron metabolism in patients with chronic kidney disease (CKD) primarily by reducing hepcidin levels and mobilizing internal iron stores. More data are needed to demonstrate the efficacy of roxadustat in regulating iron metabolism in patients with peritoneal dialysis (PD) compared with erythropoiesis stimulating agents (ESAs). METHODS: This prospective cohort study enrolled PD patients with a mean hemoglobin level of 60-100 g/L...

Age-related macular degeneration (AMD) is the most common blinding disease in the elderly population. However, there are still many uncertainties regarding the pathophysiology at the molecular level. Currently, impaired energy metabolism in retinal pigment epithelium (RPE) cells is discussed as one major hallmark of early AMD pathophysiology. Hypoxia-inducible factors (HIFs) are important modulators of mitochondrial function. Moreover, smoking is the most important modifiable risk factor for AMD and is known to impair mitochondrial integrity...

BACKGROUND: This study evaluated the comparative efficacy of roxadustat for renal anemia between patients on maintenance hemodialysis (HD) and peritoneal dialysis (PD). MATERIALS AND METHODS: 93 maintenance dialysis patients who regularly followed up from August 2015 to June 2021 were enrolled. Despite receiving a therapeutic dose ≥ 12,000 U/week of erythropoiesis-stimulating agents (E+SA) in the past 12 weeks, this had not worked very well. Subjects were assigned to the HD group (n = 60) or the PD group (n = 33) based on their dialysis treatment modality...

INTRODUCTION: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved in several regions for the treatment of anemia of chronic kidney disease (CKD). DENALI, a phase 3b study, evaluated the efficacy, safety, and feasibility of roxadustat in patients with anemia of CKD receiving in-center or home dialysis. METHODS: Eligible patients received open-label roxadustat, dosed three times weekly for 24 weeks, with an optional extension of ≤1 year...

Roxadustat (RXD) is an approved drug substances for the treatment of renal anemia. It has poor aqueous solubility and photochemical stability. This study employs a comprehensive approach to enhance the stability and physicochemical properties RXD through coformer selection and characterization. The investigation integrates delta pKa analysis, molecular complementary assessment, molecular electrostatic potential surface analysis, and machine learning techniques to predict potential co-crystal formation and binding interactions between drug molecules and coformers...

OBJECTIVE: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is a prevalent problem affecting hemodialysis (HD) patients. Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. We explored the ability of roxadustat to increase the hemoglobin (Hb) concentration in ESA-hyporesponsive patients undergoing HD and assessed its effect on iron metabolism and inflammation. METHODS: This prospective study included 30 patients with ESA-hyporesponsive anemia who had been undergoing stable dialysis...

BACKGROUND: Roxadustat is a novel oral medication used to treat anemia in CKD patients. Several studies have shown that Roxadustat can alleviate anemia in CKD patients by increasing hemoglobin levels and regulating iron metabolism. We aimed to evaluate the effect of Roxadustat on ventricular repolarization in PD patients. This study may provide a new integrated approach to the assessment and treatment of CKD. METHODS: The present prospective cohort study enrolled 65 CKD patients who were treated with Roxadustat and 31 CKD patients who received conventional therapy between January 2021 and June 2022...

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Background: Treatment for anemia of chronic kidney disease (CKD) largely consists of erythropoiesis-stimulating agents (ESAs) with iron supplementation. Although ESAs are well-established and efficacious, their use has been associated with considerable economic and humanistic burden. Roxadustat, an oral medication, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that targets multiple causes of CKD and has a similar efficacy and safety profile to ESAs. The cost-effectiveness of this treatment, however, has yet to be investigated...

The majority of lower-risk myelodysplastic syndromes/neoplasms patients present with anemia. Historically, these patients were treated with erythropoiesis-stimulating agents (ESA), with modest responses. A subset of these patients with del(5q) may do better with lenalidomide. Recently, in randomized trials, luspatercept has shown better responses compared with ESAs in treatment-naive patients and imetelstat in patients refractory to ESAs. Other evaluated novel compounds (fostamatinib, H3B-880, roxadustat, pyruvate kinase receptor activator) have not yet shown meaningful efficacy...

This study aimed to compare the utility of four different dyes for intracellular lipid detection in immortalized human meibomian gland epithelial cells (IHMGECs). IHMGECs were cultured in a serum-containing medium for 10 days in the presence or absence of Roxadustat (Roxa), a known inducer of IHMGEC differentiation. Cells were then fixed and stained with Oil Red O (ORO), Sudan III (SIII), LipidTOX green (LT), or Nile Red (NR). IHMGECs were evaluated for the number, size, and area of stained intracellular lipid vesicles or the intensity of staining using bright field (ORO, SIII) or fluorescence (LT, NR) microscopy...