Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Hepcidinanalysis.com, Nijmegen, The Netherlands.
Clin Chem Lab Med. 2020 Oct 1;59(2):315-323. doi: 10.1515/cclm-2020-0928.
Hepcidin measurement advances insights in pathophysiology, diagnosis, and treatment of iron disorders, but requires analytically sound and standardized measurement procedures (MPs). Recent development of a two-level secondary reference material (sRM) for hepcidin assays allows worldwide standardization. However, no proficiency testing (PT) schemes to ensure external quality assurance (EQA) exist and the absence of a high calibrator in the sRM set precludes optimal standardization.
We developed a pilot PT together with the Dutch EQA organization Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek (SKML) that included 16 international hepcidin MPs. The design included 12 human serum samples that allowed us to evaluate accuracy, linearity, precision and standardization potential. We manufactured, value-assigned, and validated a high-level calibrator in a similar manner to the existing low- and middle-level sRM.
The pilot PT confirmed logistical feasibility of an annual scheme. Most MPs demonstrated linearity (R2>0.99) and precision (duplicate CV>12.2%), although the need for EQA was shown by large variability in accuracy. The high-level calibrator proved effective, reducing the inter-assay CV from 42.0% (unstandardized) to 14.0%, compared to 17.6% with the two-leveled set. The calibrator passed international homogeneity criteria and was assigned a value of 9.07±0.24 nmol/L.
We established a framework for future PT to enable laboratory accreditation, which is essential to ensure quality of hepcidin measurement and its use in patient care. Additionally, we showed optimized standardization is possible by extending the current sRM with a third high calibrator, although international implementation of the sRM is a prerequisite for its success.
铁调素检测可深入了解铁代谢紊乱的病理生理学、诊断和治疗，但需要分析可靠且标准化的检测程序（MPs）。最近开发的铁调素测定二级参考物质（sRM）可实现全球标准化。然而，目前尚不存在确保外部质量保证（EQA）的能力验证（PT）方案，并且 sRM 套装中缺乏高校准品，这妨碍了最佳标准化。
我们与荷兰质量监测医学实验室诊断协会（SKML）一起开发了一个试点能力验证，其中包括 16 个国际铁调素 MPs。该设计包括 12 个人血清样本，使我们能够评估准确性、线性、精密度和标准化潜力。我们以类似于现有的低和中 sRM 的方式制造、赋值和验证高水准校准品。
试点能力验证证实了年度方案的物流可行性。大多数 MPs 表现出线性（R2>0.99）和精密度（重复 CV>12.2%），尽管准确性的巨大差异表明需要 EQA。高水平校准品证明是有效的，与两水平集相比，将测定内 CV 从 42.0%（未标准化）降低到 14.0%。与 17.6%相比，校准品通过了国际均一性标准，赋值为 9.07±0.24 nmol/L。
我们建立了未来能力验证的框架，以实现实验室认证，这对于确保铁调素检测的质量及其在患者护理中的应用至关重要。此外，我们通过扩展当前的 sRM 增加第三个高校准品，展示了优化标准化的可能性，尽管 sRM 的国际实施是其成功的前提。
