Hepcidin is not useful as a biomarker for iron needs in haemodialysis patients on maintenance erythropoiesis-stimulating agents

Tessitore, Nicola; Girelli, Domenico; Campostrini, Natascia; Bedogna, Valeria; Solero, Giovanni Pietro; Castagna, Annalisa; Melilli, Edoardo; Mantovani, William; Matteis, Giovanna De; Olivieri, Oliviero; Poli, Albino; Lupo, Antonio

doi:10.1093/ndt/gfq321

Cited by 82 publications

(80 citation statements)

References 35 publications

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“…CHD patients with sustained hyperhepcidinemia may be good candidates for the use of hepcidin antagonists [4] promote proper iron utilization for erythropoiesis. Available studies on hepcidin level as a guide to intravenous iron supplementation in CHD are limited to the observation of a lack of correlation with hemoglobin increase in relatively small and unselected populations [17]. However, the subgroup of CHD patients with repeatedly normal to low serum hepcidin levels may represent the ideal target for safe and effective iron supplementation.…”

Section: Discussionmentioning

confidence: 99%

“…To date, the relatively larger study (n = 56) did not show hepcidin as a useful predictor of hemoglobin response to i.v. iron [17]. However, this study had some limitations like possible underpowering and lack of a control group, so that larger trials comparing hepcidin-driven to standard therapeutic approaches are eagerly awaited.…”

Section: Potential Clinical Usefulness Of Hepcidin Determination In Cmentioning

confidence: 99%

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Hepcidin levels in chronic hemodialysis patients: a critical evaluation

Valenti

Pelusi

Campostrini

et al. 2014

Clinical Chemistry and Laboratory Medicine

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Altered systemic iron metabolism is a key element of uremia, and functional iron deficiency mainly related to subclinical inflammation makes it difficult to maintain proper control of anemia in chronic hemodialysis patients (CHD). In the last decade, the hepatic hormone hepcidin has been progressively recognized as the master regulator of circulating iron levels through the modulation of cellular iron fluxes in response to iron stores, as well as to erythroid and inflammatory stimuli. Hepcidin is cleared by the kidney and progression of renal disease has been associated to increased serum hepcidin levels. This, in turn, reduces iron availability for erythropoiesis, suggesting anti-hepcidin strategies for improving anemia control. Moreover, hepcidin has been recently implicated in the pathogenesis of long-term complications of dialysis, like accelerated atherosclerosis. Initial studies almost invariably reported a sustained increase of serum hepcidin in chronic hemodialysis patients. Noteworthy, such studies included relatively few patients and controls that were poorly matched for major determinants of serum hepcidin at population level, i.e., age and gender. More recent data based on accurately matched larger series challenge the view that hepcidin is intrinsically increased in hemodialysis patients, showing a marked inter-and intra-individual variability of hormone levels. Here we take a critical look to the data published so far on hepcidin levels in CHD, analyze the reasons underlying the discrepancies in available studies and the hepcidin variability in CHD, and point out the need for further studies in large series of well-characterized CHD patients and controls.

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Section: Discussionmentioning

confidence: 99%

Section: Potential Clinical Usefulness Of Hepcidin Determination In Cmentioning

confidence: 99%

Hepcidin levels in chronic hemodialysis patients: a critical evaluation

Valenti

Pelusi

Campostrini

et al. 2014

Clinical Chemistry and Laboratory Medicine

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“…Interestingly, these smaller hepcidin isoforms occur only in serum of patients with diseases that are associated with increased concentrations of hepcidin-25, such as acute myocardial infarction (AMI), 4 sepsis, anemia of chronic disease (ACD), metabolic syndrome, and chronic kidney disease (CKD) ( Fig. 2) (12)(13)(14)(15)(16)(17). In vivo studies in mice have demonstrated that only full-length 25 amino acid hepcidin induces significant hypoferremia when injected intraperitoneally (18 ).…”

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confidence: 99%

Hepcidin in Human Iron Disorders: Diagnostic Implications

et al. 2011

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BACKGROUND:The peptide hormone hepcidin plays a central role in regulating dietary iron absorption and body iron distribution. Many human diseases are associated with alterations in hepcidin concentrations. The measurement of hepcidin in biological fluids is therefore a promising tool in the diagnosis and management of medical conditions in which iron metabolism is affected.CONTENT: We describe hepcidin structure, kinetics, function, and regulation. We moreover explore the therapeutic potential for modulating hepcidin expression and the diagnostic potential for hepcidin measurements in clinical practice.

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“…Other laboratory markers have been investigated to improve the sensitivity and specificity of the detection of this condition, including serum transferrin receptor, percentage hypochromic RBCs, and reticulocyte hemoglobin content [18]. In the context of nephrology, measurement of the percentage of hypochromic RBCs in the blood has generally been found to be the optimal test, followed by reticulocyte hemoglobin content [19,20]. Serum transferrin receptor is of less value in the CKD setting, because many patients are on erythropoietin-like drugs, and enhanced erythropoiesis is one of the factors evoking an increase in serum transferrin receptor, confounding its use as a marker of iron insufficiency.…”

Section: Absolute and Functional Iron Deficiencymentioning

confidence: 99%

“…iron. Measurement of serum hepcidin has been suggested as a potential alternative in this regard, although there have been recent concerns about its variability in hemodialysis patients [59] and whether or not it is in fact any better than measurement of hypochromic RBCs [20].…”

Section: Guidelines Regardingmentioning

confidence: 99%

Iron Supplementation in Nephrology and Oncology: What Do We Have in Common?

Macdougall

2011

The Oncologist

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Anemia is frequently seen in patients with chronic kidney disease and also in those with cancer. There are factors in the pathogenesis of anemia that are common to both clinical conditions, with iron insufficiency, inflammation, and upregulation of hepcidin activity playing a part in both chronic disease states. Diagnostic laboratory markers for detecting functional iron deficiency in renal disease and oncology are not ideal, and the most widely available tests, such as serum ferritin and transferrin saturation, have poor sensitivity and specificity. Other tests incorporating a surrogate for iron sufficiency in the RBC and reticulocyte (such as percentage hypochromic RBCs or reticulocyte hemoglobin content) have greater sensitivity/specificity, but unfortunately these tests are not widely available in many hospital laboratories. Iron supplementation may be given via the oral route, i.m., or i.v., but it is now clear that, in both the nephrology and oncology settings, i.v. iron is superior to oral iron in terms of efficacy. Oral iron is associated with a high incidence of gastrointestinal side effects, and although large epidemiological studies of i.v. iron are reassuring, the long-term safety of parenteral iron is not established in well-designed adequately powered randomized controlled trials. The Oncologist 2011;16(suppl 3):25-34

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Hepcidin is not useful as a biomarker for iron needs in haemodialysis patients on maintenance erythropoiesis-stimulating agents

Abstract: Although our study suggests an important role for hepcidin in regulating iron homeostasis in HD patients on ESA, our findings do not support its utility as a predictor of iron needs, offering no advantage over established markers of iron status.

Cited by 82 publications

References 35 publications

Hepcidin levels in chronic hemodialysis patients: a critical evaluation

Hepcidin levels in chronic hemodialysis patients: a critical evaluation

Hepcidin in Human Iron Disorders: Diagnostic Implications

Iron Supplementation in Nephrology and Oncology: What Do We Have in Common?

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