Results of the first international round robin for the quantification of urinary and plasma hepcidin assays: need for standardization

Kroot, Joyce J.C.; Kemna, Erwin H.J.M.; Bansal, Sukhvinder S.; Busbridge, Mark; Campostrini, Natascia; Girelli, Domenico; Hider, Robert C.; Koliaraki, Vasiliki; Mamalaki, Avgi; Olbina, Gordana; Tomosugi, Naohisa; Tselepis, Chris; Ward, Douglas G.; Ganz, Tomas; Hendriks, Jan C.M.; Swinkels, Dorine W.

doi:10.3324/haematol.2009.010322

Cited by 167 publications

(140 citation statements)

References 17 publications

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“…There are numerous variations and modifications of MS (e.g., HPLC-MS/MS, MALDI-TOF MS, and SELDI-TOF) that have been employed by different laboratories to measure hepcidin levels in biological samples, however, the details of these modifications are beyond the scope of this paper [8][9][10][11]. One of the major benefits of measuring hepcidin by MS methodologies is the ability to distinguish and quantitate the bioactive hepcidin-25 [11].…”

Section: Mass Spectrometrymentioning

confidence: 99%

Peering into the future: Hepcidin testing

2013

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Hepcidin, a small 25 amino acid peptide, has been well established as the iron regulatory hormone. Its expression is upregulated in response to iron and inflammatory cytokines, and downregulated in anemic or hypoxic states. Hepcidin decreases iron export into the plasma by binding to and inducing the degradation of ferroportin, an iron channel located on macrophages and the basolateral surface of enterocytes. This leads to decreased absorption of parental iron by the enterocytes, reduced recycling of erythrocyte iron by macrophages, and increased iron stores in the hepatocytes. Although hepcidin assays are not currently approved for clinical use in the United States, there is much interest in the potential use of this biomarker for management of iron related medical conditions. This review briefly summarizes the current hepcidin test platforms under investigation and the challenges associated with development of a clinical assay for this biomarker. In addition, selected potential future applications hepcidin testing in the clinical setting are addressed. Am. J.

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Section: Mass Spectrometrymentioning

confidence: 99%

Peering into the future: Hepcidin testing

2013

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“…It is unclear whether some of the methods are measuring other analytes as well as hepcidin or if methods are measuring only a proportion of the hepcidin present. The international "round robin" on the first steps toward the harmonization of hepcidin measurement has also highlighted this difference in hepcidin measurements (26). Great care needs to be exercised in correlating hepcidin concentrations determined using different methods.…”

Section: Current Limitations Of Hepcidin Determinationmentioning

confidence: 99%

“…Intraday and interday analysis of clinical samples showed a precision of Ͻ10% with a LOD of 0.13 ng/ml and a lower limit of quantitation of 1.1 ng/ml. In the recently published international "round robin" study on the first steps toward harmonization of hepcidin measurement reported earlier in this review, in which each laboratory was given seven samples analyzed in triplicate on the 4 consecutive days (26), methods included SELDI (with and without internal standards) and LC MS/MS assays. In general, the means of all of the hepcidin measurements fell into a similar range, with the exception of IMAC-SELDI with external calibration yielding a mean value that was two-fold higher.…”

Section: Liquid Chromatography Ms/ms Assaysmentioning

confidence: 99%

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Current Status of the Measurement of Blood Hepcidin Levels in Chronic Kidney Disease

Macdougall¹,

Małyszko²,

Hider³

et al. 2010

Clinical Journal of the American Society of Nephrology

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Hepcidin is a small defensin-like peptide produced in the liver in response to anemia, hypoxia, or inflammation. In addition to its anti-microbial properties, it has also been found to be a key regulator of iron utilization, providing increased understanding of why chronic kidney disease patients absorb iron poorly from the gut and also why many hemodialysis patients develop functional iron deficiency in the presence of inflammation. Hepcidin synthesis is upregulated in uremia, as in other inflammatory states. The ability to measure hepcidin in biologic fluids has stimulated interest in the potential applicability of this measurement as a more informative marker of iron status than the traditional iron indices such as serum ferritin and transferrin saturation. Until recently, however, the assays for measuring hepcidin have lacked precision, accuracy, and internal validation. Over the last few years, however, several assays have become available that address these limitations. Broadly speaking, these can be divided into radioimmunoassays, ELISAs, and mass spectrometry methods. The purpose of this review is to outline the various assays available at the present time, to critique their advantages and limitations, and to report comparative data in patients with chronic kidney disease. A concern with the immunoassays is that they detect more than biologically active hepcidin-25. Mass spectrometric assays are specific for hepcidin-25 but are labor intensive and require more costly and sophisticated instrumentation. Thus, although mass spectrometry is more accurate, it is less practical for routine clinical use at the present time.

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“…26,[34][35][36] Studies are ongoing to determine whether hepcidin measurement will have diagnostic utility in CKD patients regarding iron status, inflammatory status, or ESA responsiveness or resistance. Complicating factors are the lack of uniformity in hepcidin measurements by different assays, 37 and the complex interplay of various factors that influence hepcidin levels in CKD patients, including iron, inflammation, and reduced renal clearance that tend to increase hepcidin, and anemia, ESAs, dialysis clearance, and hypoxia that tend to reduce hepcidin. 26 Recognition of a key role for hepcidin excess in causing the functional iron deficiency and anemia of CKD has ignited interestintargetingthehepcidin-ferroportin axis as a new treatment strategy for this disease.…”

mentioning

confidence: 99%

Mechanisms of Anemia in CKD

Babitt

Lin

2012

Journal of the American Society of Nephrology

822

691

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Anemia is a common feature of CKD associated with poor outcomes. The current management of patients with anemia in CKD is controversial, with recent clinical trials demonstrating increased morbidity and mortality related to erythropoiesis stimulating agents. Here, we examine recent insights into the molecular mechanisms underlying anemia of CKD. These insights hold promise for the development of new diagnostic tests and therapies that directly target the pathophysiologic processes underlying this form of anemia.

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Results of the first international round robin for the quantification of urinary and plasma hepcidin assays: need for standardization

Cited by 167 publications

References 17 publications

Peering into the future: Hepcidin testing

Peering into the future: Hepcidin testing

Current Status of the Measurement of Blood Hepcidin Levels in Chronic Kidney Disease

Mechanisms of Anemia in CKD

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