An innovative immunoassay for accurate aldosterone quantification: overcoming low-level inaccuracy and renal...

Area of Science:

• Clinical Chemistry
• Immunoassay Development
• Endocrinology

Background:

• Accurate plasma aldosterone concentration (PAC) measurement is vital for diagnosing primary aldosteronism (PA).
• Current competitive chemiluminescence immunoassays (cCLIA) often overestimate PAC compared to liquid chromatography-tandem mass spectrometry (LC-MS/MS).
• LC-MS/MS, while accurate, is not widely accessible due to its complexity and time requirements.

Purpose of the Study:

• To evaluate a novel two-step sandwich chemiluminescence immunoassay (sCLIA) for accurate PAC quantification.
• To assess the performance of sCLIA compared to cCLIA and LC-MS/MS across various clinical scenarios.
• To determine the suitability of sCLIA for large-scale PA screening.

Main Methods:

• Comprehensive validation of sCLIA's precision, linearity, and dilution factor.
• Multicenter study involving 2,696 samples analyzed in parallel by sCLIA, cCLIA, and LC-MS/MS.
• Specific evaluation of sCLIA performance at low PAC levels and in patients with chronic kidney disease (CKD).

Main Results:

• sCLIA demonstrated excellent analytical performance with low imprecision (<4.64%) and bias (<5.71%).
• The assay offers a wide reportable range (30-100,000 ng/L) and a limit of quantification of 30 ng/L.
• sCLIA showed superior agreement with LC-MS/MS compared to cCLIA, especially at low PAC concentrations and in patients with reduced eGFR.

Conclusions:

• The novel sCLIA method provides accurate PAC quantification, bridging the gap between immunoassay practicality and LC-MS/MS accuracy.
• sCLIA is a promising tool for routine clinical use, facilitating efficient and reliable PA screening.
• This assay offers an ideal solution for widespread primary aldosteronism screening in clinical practice.