Clinical interpretation of serum hepcidin-25 in inflammation and renal dysfunction

Chen, Michael X.; Kuehne, Nathan; Mattman, André; Li, Jun; Gugten, Grace van der; Wright, Bruce

doi:10.1016/j.jmsacl.2022.03.002

Cited by 3 publications

(4 citation statements)

References 66 publications

(66 reference statements)

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“…8 In addition to the differences between the analytical methods, we observed substantial variability in hepcidin concentrations between patients, which is in line with previous reports on various patient groups. 6,26 The interindividual variability may be due to heterogeneous patient groups. At admission, factors such as degree of inflammation, duration of symptoms, and comorbidities may contribute to the observed variability.…”

Section: Discussionmentioning

confidence: 99%

Hepcidin analysis in pneumonia: Comparison of immunoassay and LC-MS/MS

Oppen

Brede²,

Skadberg³

et al. 2023

Ann Clin Biochem

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Background. The iron-regulatory hormone hepcidin is a promising biomarker to differentiate anemia of inflammation from iron deficiency. Plasma hepcidin concentrations increase substantially during inflammation, and the amount of smaller, non-biologically active isoforms of hepcidin increase in inflammatory conditions. These smaller isoforms are measured in some, but not all analytical methods. Thus, we evaluated the comparability of two analytical methods with different isoform selectivity during and after acute-phase pneumonia as a highly inflammatory model disease. Methods. Blood samples from a cohort of 267 hospitalized community-acquired pneumonia patients collected at admission and a 6-week follow-up were analysed. Hepcidin was measured in plasma by an immunoassay which recognizes all hepcidin isoforms and a liquid chromatography tandem mass spectrometry (LC-MS/MS) which selectively measures the bioactive hepcidin-25. Additionally, a subset of serum samples was analysed by LC-MS/MS. Results. Hepcidin measurements by immunoassay were higher compared with LC-MS/MS. The relative mean difference of hepcidin plasma concentrations between the two analytical methods was larger in admission samples than in follow-up samples (admission samples <200 ng/mL: 37%, admission samples >200 ng/mL: 78%, follow-up samples >10 ng/mL: 22%). During acute-phase pneumonia, serum concentrations were on average 22% lower than plasma concentrations when measured by LC-MS/MS. Conclusions. Immunoassay measured higher hepcidin concentrations compared with LC-MS/MS, with more pronounced differences in high concentration samples during acute-phase pneumonia. These findings should be considered in local method validations and in future harmonization and standardization optimization of hepcidin measurements.

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Section: Discussionmentioning

confidence: 99%

Hepcidin analysis in pneumonia: Comparison of immunoassay and LC-MS/MS

Oppen

Brede²,

Skadberg³

et al. 2023

Ann Clin Biochem

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“…This study further proposed cut‐off points to differentiate IDA (serum hepcidin ≤2.735 ng/mL) from ID (serum hepcidin ≤6.895 ng/mL). In another study of adults with renal dysfunction, the hepcidin index (log[hepcidin]:log[ferritin] ratio) was noted to better predict ID (39).…”

Section: Physiology Of Iron Absorption In Irmentioning

confidence: 99%

Evaluation and Management of Iron Deficiency in Children Undergoing Intestinal Rehabilitation—A Position Paper From the NASPGHAN Intestinal Rehabilitation Special Interest Group

Talathi¹,

Namjoshi²,

Wendel

et al. 2023

Journal of Pediatric Gastroenterology &Amp; Nutrition

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Iron deficiency (ID) is the most common nutritional deficiency affecting children undergoing intestinal rehabilitation (IR). Patients may be asymptomatic or present with nonspecific symptoms including fatigue, irritability, and dizziness. The diagnosis of ID in this population can be complicated by the coexistence of systemic inflammation or other nutritional deficiencies which may mimic ID. Many routinely available laboratory tests lack specificity and no consensus on screening is available. Success in oral and enteral treatment is impeded by poor tolerance of iron formulations in a population already challenged with intolerance. Newer parenteral iron formulations exhibit excellent safety profiles, but their role in repletion in this population remains unclear. The following report, compiled by a multidisciplinary group of providers caring for children undergoing IR and representing the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Special Interest Group for Intestinal Rehabilitation, seeks to address these challenges. After discussing iron physiology and population-specific pathophysiology, we make recommendations on iron intake, iron status assessment, and evaluation for alternative causes of anemia. We then provide recommendations on iron supplementation and treatment of ID anemia specific to this nutritionally vulnerable population.

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“…Hepcidin is a liver-derived peptide hormone that principally regulates systemic iron homeostasis and its biological activity is primarily determined by hepcidin-25, a 25 amino acid peptide. 19,20 Hepcidin binds the iron transporter ferroportin, leading to ubiquitination and degradation. 21 Ferroportin is the only iron transporter in the body, and its degradation results in abrogation of gastrointestinal iron absorption and reticuloendothelial iron recycling.…”

Section: Introductionmentioning

confidence: 99%

“…Inflammation drives these processes by inducing elevated levels of hepcidin, a master regulator of iron homeostasis. Hepcidin is a liver‐derived peptide hormone that principally regulates systemic iron homeostasis and its biological activity is primarily determined by hepcidin‐25, a 25 amino acid peptide 19,20 . Hepcidin binds the iron transporter ferroportin, leading to ubiquitination and degradation 21 .…”

Section: Introductionmentioning

confidence: 99%

First‐in‐Human Phase 1 Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of DISC‐0974, an Anti‐Hemojuvelin Antibody, in Healthy Participants

Novikov,

Buch,

Yang

et al. 2024

The Journal of Clinical Pharma

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Pathologic elevations in hepcidin, a key regulator of iron homeostasis, contribute to anemia of inflammation in chronic disease. DISC‐0974 is a monoclonal antibody that binds to hemojuvelin and blocks bone morphogenetic protein signaling, thereby suppressing hepcidin production. Reduction of systemic hepcidin levels is predicted to increase iron absorption and mobilize stored iron into circulation, where it may be utilized by red blood cell (RBC) precursors in the bone marrow to improve hemoglobin levels and to potentially alleviate anemia of inflammation. We conducted a first‐in‐human, double‐blind, placebo‐controlled, single‐ascending dose study to evaluate safety, pharmacokinetics, and pharmacodynamics of DISC‐0974 in healthy participants. Overall, 42 participants were enrolled and received a single dose of placebo or DISC‐0974 at escalating dose levels (7–56 mg), administered intravenously (IV) or subcutaneously (SC). DISC‐0974 was well tolerated, with a safety profile comparable to that of placebo. Pharmacokinetic data was dose and route related, with a terminal half‐life of approximately 7 days. The bioavailability of SC dosing was ∼50%. Pharmacodynamic data showed dose‐dependent decreases in serum hepcidin, with reductions of nearly 75% relative to baseline at the highest dose level tested, and corresponding increases in serum iron in response to DISC‐0974 administration. Dose‐dependent changes in serum ferritin and hematology parameters were also observed, indicating mobilization of iron stores and downstream effects of enhanced hemoglobinization and production of RBCs. Altogether, these data are consistent with the mechanism of action of DISC‐0974 and support the selection of a biologically active dose range for evaluation in clinical trials for individuals with anemia of inflammation.

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Clinical interpretation of serum hepcidin-25 in inflammation and renal dysfunction

Cited by 3 publications

References 66 publications

Hepcidin analysis in pneumonia: Comparison of immunoassay and LC-MS/MS

Hepcidin analysis in pneumonia: Comparison of immunoassay and LC-MS/MS

Evaluation and Management of Iron Deficiency in Children Undergoing Intestinal Rehabilitation—A Position Paper From the NASPGHAN Intestinal Rehabilitation Special Interest Group

First‐in‐Human Phase 1 Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of DISC‐0974, an Anti‐Hemojuvelin Antibody, in Healthy Participants

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