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Toward Worldwide Hepcidin Assay Harmonisation: Identification of a Commutable Secondary Reference Material

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Lisa can der Vorm, Jan C. M. Hendriks, Coby M. M. Laarakkers, Siem Klaver, A Armitage, Alison Bamberg, Annrkre J Guests-Moespot, Domenico Girelli, Matthias Herbert, Outi Itkonen, Robert Konrad, Naohisa Tomosugi, Mark Westerman, Sukhvinder Bansal, Natascia Campostrini, Hal Drakesmith, Gordana Olbina, Marianne Fillet, Gordana Olbina, Sant-Rayn Pasricha & 5 more Kelly Pitts, John Sloan, Franco Tagliaro, Cas Weykamp, Dorine W. Swinkels

Original languageEnglish
Pages (from-to)991-1001
Number of pages9
JournalClinical Chemistry
Issue number7
Early online date12 May 2016
Accepted/In press7 Apr 2016
E-pub ahead of print12 May 2016
PublishedJul 2016

King's Authors


BACKGROUND: Absolute plasma hepcidin concentrations measured by various procedures differ substantially, complicating interpretation of results and rendering reference intervals method dependent. We investigated the degree of equivalence achievable by harmonization and the identification of a commutable secondary reference material to accomplish this goal.

METHODS: We applied technical procedures to achieve harmonization developed by the Consortium for Harmonization of Clinical Laboratory Results. Eleven plasma hepcidin measurement procedures (5 mass spectrometry based and 6 immunochemical based) quantified native individual plasma samples (n = 32) and native plasma pools (n = 8) to assess analytical performance and current and achievable equivalence. In addition, 8 types of candidate reference materials (3 concentrations each, n = 24) were assessed for their suitability, most notably in terms of commutability, to serve as secondary reference material.

RESULTS: Absolute hepcidin values and reproducibility (intrameasurement procedure CVs 2.9%–8.7%) differed substantially between measurement procedures, but all were linear and correlated well. The current equivalence (intermeasurement procedure CV 28.6%) between the methods was mainly attributable to differences in calibration and could thus be improved by harmonization with a common calibrator. Linear regression analysis and standardized residuals showed that a candidate reference material consisting of native lyophilized plasma with cryolyoprotectant was commutable for all measurement procedures. Mathematically simulated harmonization with this calibrator resulted in a maximum achievable equivalence of 7.7%.

CONCLUSIONS: The secondary reference material identified in this study has the potential to substantially improve equivalence between hepcidin measurement procedures and contributes to the establishment of a traceability chain that will ultimately allow standardization of hepcidin measurement results.

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