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An innovative immunoassay for accurate aldosterone quantification: overcoming low-level inaccuracy and renal dysfunction-associated interference

  • Kaijuan Wang ORCID logo EMAIL logo , Hongying Cong , Zhangwei Gao , Xiaojing Gao , Wei Zhang , Xiaocui Shi and Zhou Zhou EMAIL logo
Published/Copyright: August 25, 2025
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 12

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.

Keywords: aldosterone; sandwich chemiluminescent immunoassay; primary aldosteronism; interference; LC-MS/MS; chronic kidney disease
Corresponding authors: Kaijuan Wang and Zhou Zhou, Center of Laboratory Medicine, Beijing Key Laboratory of Cardiovascular Disease Warning and Diagnosis, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College/National Center for Cardiovascular Diseases, Beijing, 100037, China, E-mail: (K. Wang), (Z. Zhou)

Funding source: CAMS Innovation Fund for Medical Sciences (CIFMS)

Award Identifier / Grant number: 2023-I2M-C&T-B-062

Funding source: Noncommunicable Chronic Diseases-National Science and Technology Major Project

Award Identifier / Grant number: 2024ZD0533201

  1. Research ethics: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the Ethics Committee of Fuwai Hospital (2023–2260) and the other six participating hospitals.

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: This study was funded by the CAMS Innovation Fund for Medical Sciences (CIFMS, 2023-I2M-C&T-B-062), Noncommunicable Chronic Diseases-National Science and Technology Major Project (2024ZD0533200).

  7. Data availability: The data that support the findings of this study are available from the corresponding author[Zhou Zhou], upon reasonable request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0743).

Received: 2025-06-16
Accepted: 2025-08-10
Published Online: 2025-08-25
Published in Print: 2025-11-25

© 2025 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

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  2. Editorials
  3. Challenging the dogma: why reviewers should be allowed to use AI tools
  4. Multivariate approaches to improve the interpretation of laboratory data
  5. Review
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  7. Opinion Papers
  8. Urgent call to the European Commission to simplify and contextualize IVDR Article 5.5 for tailored and precision diagnostics
  9. The importance of laboratory medicine in the management of CKD-MBD: insights from the KDIGO 2023 controversies conference
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  38. Permitting disclosed AI assistance in peer review: parity, confidentiality, and recognition
  39. Response to the editorial by Karl Lackner
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https://doi.org/10.1515/cclm-2025-0743
Keywords for this article
aldosterone; sandwich chemiluminescent immunoassay; primary aldosteronism; interference; LC-MS/MS; chronic kidney disease

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Challenging the dogma: why reviewers should be allowed to use AI tools
  4. Multivariate approaches to improve the interpretation of laboratory data
  5. Review
  6. Interference of therapeutic monoclonal antibodies with electrophoresis and immunofixation of serum proteins: state of knowledge and systematic review
  7. Opinion Papers
  8. Urgent call to the European Commission to simplify and contextualize IVDR Article 5.5 for tailored and precision diagnostics
  9. The importance of laboratory medicine in the management of CKD-MBD: insights from the KDIGO 2023 controversies conference
  10. Supplementation of pyridoxal-5′-phosphate in aminotransferase reagents: a matter of patient safety
  11. HCV serology: an unfinished agenda
  12. From metabolic profiles to clinical interpretation: multivariate approaches to population-based and personalized reference intervals and reference change values
  13. Genetics and Molecular Diagnostics
  14. A multiplex allele specific PCR capillary electrophoresis (mASPCR-CE) assay for simultaneously analysis of SMN1/SMN2/NAIP copy number and SMN1 loss-of-function variants
  15. General Clinical Chemistry and Laboratory Medicine
  16. From assessment to action: experience from a quality improvement initiative integrating indicator evaluation and adverse event analysis in a clinical laboratory
  17. Evaluation of measurement uncertainty of 11 serum proteins measured by immunoturbidimetric methods according to ISO/TS 20914: a 1-year laboratory data analysis
  18. Assessing the harmonization of current total vitamin B12 measurement methods: relevance and implications
  19. The current status of serum insulin measurements and the need for standardization
  20. Method comparison of plasma and CSF GFAP immunoassays across multiple platforms
  21. Cerebrospinal fluid leptin in Alzheimer’s disease: relationship to plasma levels and to cerebrospinal amyloid
  22. Verification of the T50 Calciprotein Crystallization test: bias estimation and interferences
  23. An innovative immunoassay for accurate aldosterone quantification: overcoming low-level inaccuracy and renal dysfunction-associated interference
  24. Oral salt loading combined with postural stimulation tests for confirming and subtyping primary aldosteronism
  25. Evaluating the performance of a multiparametric IgA assay for celiac disease diagnosis
  26. Clinical significance of anti-mitochondrial antibodies and PBC-specific anti-nuclear antibodies in evaluating atypical primary biliary cholangitis with normal alkaline phosphatase levels
  27. Reference Values and Biological Variations
  28. Establishment of region-, age- and sex-specific reference intervals for aldosterone and renin with sandwich chemiluminescence immunoassays
  29. Validation of a plasma GFAP immunoassay and establishment of age-related reference values: bridging analytical performance and routine implementation
  30. Comparative analysis of population-based and personalized reference intervals for biochemical markers in peri-menopausal women: population from the PALM cohort study
  31. Hematology and Coagulation
  32. Evaluation of stability and potential interference on the α-thalassaemia early eluting peak and immunochromatographic strip test for α-thalassaemia --SEA carrier screening
  33. Cardiovascular Diseases
  34. Analytical and clinical evaluation of an automated high-sensitivity cardiac troponin I assay for whole blood
  35. Diabetes
  36. Method comparison of diabetes mellitus associated autoantibodies in serum specimens
  37. Letters to the Editor
  38. Permitting disclosed AI assistance in peer review: parity, confidentiality, and recognition
  39. Response to the editorial by Karl Lackner
  40. Hemolysis detection using the GEM 7000 at the point of care in a pediatric hospital setting: does it affect outcomes?
  41. Estimation of measurement uncertainty for free drug concentrations using ultrafiltration
  42. Cryoglobulin pre-analysis over the weekend
  43. Accelerating time from result to clinical action: impact of an automated critical results reporting system
  44. Recent decline in patient serum folate test levels using Roche Diagnostics Folate III assay
  45. Kidney stones consisting of 1-methyluric acid
  46. Congress Abstracts
  47. 7th EFLM Conference on Preanalytical Phase
  48. Association of Clinical Biochemists in Ireland Annual Conference
  49. Association of Clinical Biochemists in Ireland Annual Conference
  50. 17th Congress of the Portuguese Society of Clinical Chemistry, Genetics and Laboratory Medicine
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