Auryxia (ferric citrate) / Japan Tobacco, Akebia Therap, Averoa - LARVOL DELTA

Cleavage cascade of the sigma regulator FecR orchestrates TonB-dependent signal transduction. (PubMed, Proc Natl Acad Sci U S A) - "Consequently, the successive cleavage of FecR's NTD is initiated, culminating in the ferric citrate signal-induced activation of fec gene expression. Our findings reveal that the regulation of FecR cleavage, controlled by the TonB-FecA axis, plays a central role in the bacterial response to ferric citrate signals."

Journal • Infectious Disease • Targeted Protein Degradation

Study to Evaluate the Safety and Tolerability of Ferric Citrate in Children With Hyperphosphatemia Related to Chronic Kidney Disease (clinicaltrials.gov) - P3 | N=45 | Recruiting | Sponsor: Keryx Biopharmaceuticals | Trial completion date: Jun 2025 ➔ Oct 2026 | Trial primary completion date: Jan 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

Iron overload mediates cytarabine resistance in AML by inhibiting the TP53 signaling pathway. (PubMed, Acta Biochim Biophys Sin (Shanghai)) - "In this study, an iron overload model in AML cells via the use of ferric citrate is constructed. In TP53 wild-type AML cells, TFR1 participates in iron-mediated resistance to cytarabine by regulating the entry of iron into the cells. These findings provide a foundation for further exploration of the molecular mechanisms involved in AML resistance to cytarabine."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • BCL2 • TFRC

Vadadustat Combination with Ferric Citrate, Compared to Either Agent Alone, Protects Against Inflammation-Induced Anaemia and Anaemia-Induced by Chronic Kidney Disease (ERA 2025) - No abstract available

Anemia • Chronic Kidney Disease • Hematological Disorders • Inflammation • Nephrology • Renal Disease

AVEROA Receives Positive Opinion from the European Medicines Agency for XOANACYL, an Oral Therapy for Chronic Kidney Disease (CKD) (GlobeNewswire) - "Averoa...announces a positive opinion from the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) for XOANACYL, an oral therapy for chronic kidney disease (CKD). This milestone represents a key step toward a potential EU- approval."

CHMP • Chronic Kidney Disease

Akebia Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Vafseo (vadadustat) Commercial Launch Progress Update (GlobeNewswire) - "Akebia Therapeutics, Inc...As previously announced, Vafseo (vadadustat) shipments to customers began January 9, 2025. Akebia expects Vafseo first quarter 2025 net product revenues of approximately $10-$11 million...We expect to initiate the VALOR study in the second half of this year...Auryxia (ferric citrate) net product revenues were $44.4 million in the fourth quarter of 2024 compared to $53.2 million in the fourth quarter of 2023, and $152.2 million for the full-year 2024 compared to $170.3 million for the full-year 2023."

Commercial • Launch US • New P3 trial • Sales projection • Anemia • Chronic Kidney Disease • Hematological Disorders • Renal Disease

Efficacy and Safety of Phosphate-Lowering Agents for Adult Patients with Chronic Kidney Disease Requiring Dialysis: A Network Meta-Analysis. (PubMed, Clin J Am Soc Nephrol) - "Compared with calcium-based agents, sevelamer was associated with lower all-cause mortality, and sucroferric oxyhydroxide and lanthanum were associated with slower progression of CACS. Potential benefits and harms should be considered when selecting phosphate-lowering agents (PROSPERO: CRD42022328388)."

Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Gastrointestinal Disorder • Musculoskeletal Diseases • Nephrology • Renal Disease

A Multicenter Single-Arm Study of Switching to Ferric Citrate Hydrate for Iron Deficiency Anemia in Patients Intolerant to Oral Iron: RIO-SWITCH. (PubMed, Adv Ther) - "FCH treatment exhibited a satisfactory medication completion rate in patients with IDA. Switching to FCH reduced N/V incidence and improved N/V and QoL severity compared with previous oral iron preparations."

Journal • Anemia • Gastrointestinal Disorder • Hematological Disorders

Ferric citrate corroding nickel foam to synthesize carbon quantum dots@nickel-iron layered double hydroxide microspheres for efficient water oxidation. (PubMed, J Colloid Interface Sci) - "Furthermore, CQDs@NiFe-LDH can be operated continuously for 300 and 100 h without the significant performance degradation at a current density of 100 mA cm-2 in 1 M KOH and seawater solutions, respectively, indicating high catalytic stability. The excellent OER capabilities of CQDs@NiFe-LDH is attributed to the fact that CQDs can not only modulate the electronic structure of NiFe-LDH but also facilitate the transfer of protons between intermediates during the oxygen evolution reaction (OER), thereby enhancing the material's intrinsic catalytic activity."

Journal

Association of iron-acquisition-related genes and milk lactoferrin concentration with the growth of Escherichia coli and Klebsiella pneumoniae in milk of dairy cows. (PubMed, Microb Pathog) - "LF levels and SCCs in milk were significantly and negatively correlated with bacterial counts at 6 h in the milk growth experiment. These results suggested that the ferric-citrate-uptake systems of E. coli and K. pneumoniae may strongly contribute to their proliferation in mammary glands in dairy cows, whereas a high LF concentration in milk may successfully inhibit the growth of K. pneumoniae."

Journal • Infectious Disease • Pneumonia

Brain iron metabolism impairment differs between aged mouse models of cerebral hypoperfusion and iron overload (ISC 2025) - "Two weeks after surgery, mice were administered 5% ferric citrate (FC, 3 alternate days/week for 6 weeks) by oral gavage as a model of iron overload or were given saline solution... BCAS and FC affect brain function via different mechanisms, and the combination of both does not worsen the phenotype. BCAS, but not FC, increased the expression of Gss and Ncoa4. Next, we will determine whether ferritinophagy is activated in the brains of BCAS mice and whether the higher expression of Gss is a response to mitigate the oxidative stress induced by CCH."

Preclinical • Cardiovascular • CNS Disorders • Cognitive Disorders • Hematological Disorders • NCOA4

Iron sequestration contributes to the limited efficacy of enteral iron supplementation in the treatment of anemia of chronic kidney disease in young mice (IPNA 2025) - "Methods To evaluate iron sequestration during CKD, we induced CKD in wild type (WT) and macrophage-specific ( LysM -Cre) ferroportin (Fpt) knockout (KO) mice using a 0.2% adenine diet in the absence or presence of carbonyl iron, ferrous sulfate, or ferric citrate supplementation...Oral iron supplementation further enhanced iron sequestration, disproportionately to the alleviation of anemia in CKD mice. Sequestered iron remained partially mobilizable."

Preclinical • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Pediatrics • Renal Disease • FTL

Subtle genomic differences in Klebsiella pneumoniae sensu stricto isolates indicate host adaptation. (PubMed, One Health) - "However, subtle genetic differences exist between bovine and human KpI which likely reflect environmental adaptation to different host niches, including a higher representation of gene clusters encoding ferric citrate uptake transporters, as well as histidine, arginine, and lactose utilization pathways in bovine isolates. These gene clusters may be positively selected due to the unique metabolic environment of the mammary gland, where lactose, citrate-bound iron, and amino acids like histidine and arginine provide growth advantages for KpI during mastitis. Overall, our study identified no obvious genetic barriers to zoonotic transmission of KpI within the dairy environment and provides insight into the development of host-specific therapeutic options for KpI infections in humans and bovine."

Journal • Infectious Disease • Pneumonia

Deferasirox improved iron homeostasis and hematopoiesis in ovariectomized rats with iron accumulation. (PubMed, Sci Rep) - "Iron accumulation was induced through the injection of ammonium ferric citrate...Deferasirox had a positive effect on femur bone, hematopoietic cell count, volume of hematopoietic and adipose tissues in bone marrow, extramedullary hematopoiesis in the liver and spleen, and influenced the relative expression of Hamp, Pu.1, Gata1, and Gdf11 genes related to hematopoiesis and iron metabolism. In conclusion, Deferasirox effectively manages iron homeostasis and hematopoiesis in ovariectomized rats with iron accumulation and suppresses oxidative stress."

Journal • Preclinical • Hematological Disorders • GATA1 • HAMP

Alkane degradation coupled to Fe(III) reduction mediated by Gram-positive bacteria. (PubMed, J Hazard Mater) - "When ferric citrate was used as the electron acceptor, strains SL-6A and SL-12A degraded 94.2 % and 87.4 % of n-C16, respectively, within 72 hours...Whole-genome sequencing confirmed the pathways for n-alkane degradation and the synthesis of c-Cyts and FMN in our strains. This research highlights the potential of electroactive Gram-positive bacteria in hydrocarbon degradation in contaminated soils."

Journal • Infectious Disease

Cost-effectiveness of ferric citrate hydrate in patients with iron deficiency anemia. (PubMed, Int J Hematol) - "Treatment with FC for IDA was cost-effective (ICER ≤ JPY 5,000,000/QALY) when switching strategies from the payer perspective, and cost-saving (all FC strategies) from limited societal perspectives. Individual patients' characteristics and cost-effectiveness should be considered in treatment selection."

HEOR • Journal • Anemia • Gastrointestinal Disorder • Hematological Disorders

Cefiderocol Resistance Conferred by Plasmid-Located Ferric Citrate Transport System in KPC-Producing Klebsiella pneumoniae. (PubMed, Emerg Infect Dis) - "coli cells treated with ferric citrate. Screening of 27,793 K. pneumoniae whole-genome sequences revealed that the fec cluster occurs frequently in some globally distributed different KPC-producing K. pneumoniae clones (sequence types 258, 14, 45, and 512), contributing to reduced FDC susceptibility."

Journal • Infectious Disease • Pneumonia

Increased Trypanocidal Activity of the Salinomycin Derivative Ironomycin Is Due to ROS Production and Iron Uptake Impairment. (PubMed, Molecules) - "However, when bloodstream-form trypanosomes were incubated with ironomycin in the presence of vitamin E and ammonium ferric citrate, the trypanocidal activity of the compound was reduced to that of salinomycin (GI50 = 0.21 μM vs. GI50 = 0.20 μM). Moreover, ironomycin caused a reduction in the uptake of the iron-carrier protein transferrin mediated by a downregulation of the transferrin receptor and led to the accumulation and sequestering of iron(II) in the parasite's lysosome, triggering an increase production of reactive oxygen species (ROS). These results suggest that the increased trypanocidal activity of ironomycin can be mainly attributed to an increased ROS production and, to a lesser extent, an impairment in iron uptake."

Journal

Acute endothelial stresses identify microRNA let-7b-5p and non-coding SLC11A2 (NRAMP2/DMT1) exon as biomarkers that overlap with those detected in malignant and non-malignant diseases. (PubMed, QJM) - "Biomarkers for normal, acute cellular responses overlap with disease-state biomarkers, warranting further study."

Biomarker • Journal • Oncology • DMRT1 • MIRLET7B • SLC11A2

Monocytic Leukemia Cell Resistance to Ferroptosis Is Overcome By Iron Chelation (ASH 2024) - "Erastin is known to be largely ineffective as a ferroptosis-inducer in THP-1 cells and other leukemic cell lines.Methods : THP-1 cells were cultured in various concentrations of ferric citrate or deferoxamine (DFO) for 96 hours to simulate chronic states of iron excess and deficiency, respectively. It also provides novel evidence of ferric citrate attenuating THP-1 cell resistance to erastin and, most notably, a synergistic lethality between an iron chelator and ferroptosis-inducer (DFO and erastin). This result suggests a novel avenue of antileukemic combination therapy that has potential to combat the poor prognoses of AMoL and acute leukemias, more broadly."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • GPX4

Endogenous plasma resuspension of peripheral blood mononuclear cells prevents preparative-associated stress that modifies polyA-enriched RNA responses to subsequent acute stressors. (PubMed, Cell Stress) - "Plasma-resuspended PBMCs demonstrated minor transcriptome changes after 40 μmol/L ferric citrate, whereas consistent and greater magnitude changes were observed for washed/media-resuspended PBMCs. We conclude that endogenous plasma-maintained PBMCs provide a more robust platform to interrogate acute cellular perturbations triggering innate immunity, and that varying susceptibility of PBMCs to preparative stresses is an important component of experimental variability."

Journal • IL1B

Physiological iron chelators pyrophosphate and citrate have different effects on the proportions of monoferric transferrin metalloforms. (PubMed, J Inorg Biochem) - "Ferric pyrophosphate and ferric citrate have been shown to direct loading into the C-lobe and N-lobe, respectively...This indicates that pyrophosphate may play a physiological role in transferrin iron loading and body iron homeostasis. We also present a validation of an existing micellar capillary electrophoresis technique for separating the four transferrin metalloforms, which has potential to be adapted for use in a clinical setting."

Journal

Rigid-Flexible Coupling Realized by Synergistic Engineering of the Graphitic-Amorphous Architecture for Durable and Fast Potassium Storage. (PubMed, Adv Sci (Weinh)) - "Herein, a partial graphitic carbon (PGC) is elaborately engineered via the catalytic effect of ferric citrate using pitch as a carbon precursor...In-situ XRD and DFT simulations further verify the distinct phase transition mechanisms and reaction dynamics across different carbon configurations. This work elucidates the impact of carbon configurations on K-storage performance and proposes a structural model for efficient K-ion storage, which is instrumental in the rational design and advancement of carbon anodes in PIBs."

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A critical role for iron import through the transferrin receptor in developing ß-cells (ESPE 2024) - " To chemically modulate iron levels, mouse and human pancreatic islets, EndoC-ßH1 and human induced pluripotent stem cell (iPSC)-derived ß-cells were exposed to deferoxamine (DFO) or ferric citrate (FeCitr) for 24 hours to induce iron depletion or overload, respectively. ß-cells demonstrate unique age and maturation-dependent responses to alterations in iron supply within the endocrine pancreas. TFRC-mediated iron import is crucial for ß-cell survival and function during ß-cell development, whereas this becomes dispensable in adulthood and mature stages of iPSC-derived ß-cell differentiation. These findings underscore an intricate relationship between iron metabolism and developmental ß-cell physiology, offering potential implications for improving the functional maturation of stem cell-derived ß-cells."

Late-breaking abstract • Diabetes • Hematological Disorders • Metabolic Disorders • GCG

Iron fortification modifies the microbial community structure and metabolome of a model surface-ripened cheese. (PubMed, Int J Food Microbiol) - "Three different iron compounds (ferrous sulfate, ferric chloride, ferric citrate) were used at three different concentrations, i.e., 18, 36, and 72 μM, to fortify cheese curd after inoculation with the consortium...These findings highlight the importance of iron availability for the behavior of cheese microbial communities. They also open novel perspectives on cheesemakers' use of iron fortification to control microbial growth and improve cheese quality."

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