{"title":"An innovative immunoassay for accurate aldosterone quantification: overcoming low-level inaccuracy and renal dysfunction-associated interference.","authors":"Kaijuan Wang, Hongying Cong, Zhangwei Gao, Xiaojing Gao, Wei Zhang, Xiaocui Shi, Zhou Zhou","doi":"10.1515/cclm-2025-0743","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Accurate quantification of aldosterone is critical for screening and diagnosing primary aldosteronism (PA). Current competitive chemiluminescence immunoassays (cCLIA) overestimate plasma aldosterone concentration (PAC) compared to liquid chromatography-tandem mass spectrometry (LC-MS/MS). However, LC-MS/MS is technically demanding and time-consuming, limiting its widespread clinical utility. Therefore, a novel two-step sandwich chemiluminescence immunoassay (sCLIA) for accurate quantification of PAC was systematically evaluated.</p><p><strong>Methods: </strong>Precision, trueness, linear range, and maximum dilution factor of the new immunoassay were comprehensively validated. In a multicenter study involving 2,696 samples from seven Chinese centers, PAC measurements were performed in parallel using sCLIA, cCLIA, and LC-MS/MS. The study specifically focused on evaluating the assay's performance at low aldosterone concentrations and in patients with chronic kidney disease (CKD), investigating potential interference from renal impairment by comparing the consistency between immunoassays and LC-MS/MS results across different CKD stages.</p><p><strong>Results: </strong>The sCLIA exhibited excellent analytical performance for PAC measurement, with intra-assay imprecision <4.64 % and bias <5.71 % against certificated reference materials. The assay exhibited a wide reportable range (30-100,000 ng/L) with a limit of quantification at 30 ng/L and dilution capability ≥50-fold. Compared to cCLIA, sCLIA showed superior agreement with LC-MS/MS, particularly at low PAC concentrations (<110 ng/L) and in subjects with reduced renal function (eGFR<60 mL/min/1.73 m<sup>2</sup>).</p><p><strong>Conclusions: </strong>This novel sCLIA method exhibited excellent analytical performance, combining the practical advantages of immunoassays with LC-MS/MS accuracy, thereby offering an ideal solution for large-scale primary aldosteronism screening in clinical practice.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical chemistry and laboratory medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1515/cclm-2025-0743","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: Accurate quantification of aldosterone is critical for screening and diagnosing primary aldosteronism (PA). Current competitive chemiluminescence immunoassays (cCLIA) overestimate plasma aldosterone concentration (PAC) compared to liquid chromatography-tandem mass spectrometry (LC-MS/MS). However, LC-MS/MS is technically demanding and time-consuming, limiting its widespread clinical utility. Therefore, a novel two-step sandwich chemiluminescence immunoassay (sCLIA) for accurate quantification of PAC was systematically evaluated.
Methods: Precision, trueness, linear range, and maximum dilution factor of the new immunoassay were comprehensively validated. In a multicenter study involving 2,696 samples from seven Chinese centers, PAC measurements were performed in parallel using sCLIA, cCLIA, and LC-MS/MS. The study specifically focused on evaluating the assay's performance at low aldosterone concentrations and in patients with chronic kidney disease (CKD), investigating potential interference from renal impairment by comparing the consistency between immunoassays and LC-MS/MS results across different CKD stages.
Results: The sCLIA exhibited excellent analytical performance for PAC measurement, with intra-assay imprecision <4.64 % and bias <5.71 % against certificated reference materials. The assay exhibited a wide reportable range (30-100,000 ng/L) with a limit of quantification at 30 ng/L and dilution capability ≥50-fold. Compared to cCLIA, sCLIA showed superior agreement with LC-MS/MS, particularly at low PAC concentrations (<110 ng/L) and in subjects with reduced renal function (eGFR<60 mL/min/1.73 m2).
Conclusions: This novel sCLIA method exhibited excellent analytical performance, combining the practical advantages of immunoassays with LC-MS/MS accuracy, thereby offering an ideal solution for large-scale primary aldosteronism screening in clinical practice.
期刊介绍:
Clinical Chemistry and Laboratory Medicine (CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. CCLM welcomes contributions on the progress in fundamental and applied research and cutting-edge clinical laboratory medicine. It is one of the leading journals in the field, with an impact factor over 3. CCLM is issued monthly, and it is published in print and electronically.
CCLM is the official journal of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) and publishes regularly EFLM recommendations and news. CCLM is the official journal of the National Societies from Austria (ÖGLMKC); Belgium (RBSLM); Germany (DGKL); Hungary (MLDT); Ireland (ACBI); Italy (SIBioC); Portugal (SPML); and Slovenia (SZKK); and it is affiliated to AACB (Australia) and SFBC (France).
Topics:
- clinical biochemistry
- clinical genomics and molecular biology
- clinical haematology and coagulation
- clinical immunology and autoimmunity
- clinical microbiology
- drug monitoring and analysis
- evaluation of diagnostic biomarkers
- disease-oriented topics (cardiovascular disease, cancer diagnostics, diabetes)
- new reagents, instrumentation and technologies
- new methodologies
- reference materials and methods
- reference values and decision limits
- quality and safety in laboratory medicine
- translational laboratory medicine
- clinical metrology
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