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

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 m 2 ). 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.