A diagnostic strategy for primary aldosteronism diagnosis based on urinary aldosterone assay

To compare 24-h urinary excretion of aldosterone (24-h UEA) measured by competitive chemiluminescent immunoassay (cCLIA) and sandwich chemiluminescent immunoassay (sCLIA) with liquid chromatography-tandem mass spectrometry (LC-MS/MS), and to evaluate a direct renin concentration (DRC)-stratified interpretive strategy for primary aldosteronism (PA).

We prospectively enrolled 705 hypertensive inpatients, including 105 with PA and 600 with essential hypertension. 24-h UEA was measured by cCLIA, sCLIA, and LC-MS/MS, and DRC was measured by CLIA. Method agreement was assessed using Passing-Bablok regression and Bland-Altman analysis. Diagnostic performance was evaluated using receiver operating characteristic (ROC), with internal validation by 1,000 outcome-stratified bootstrap resamples.

Both CLIAs correlated strongly with LC-MS/MS (Spearman r=0.946 for cCLIA and 0.950 for sCLIA). Overall areas under the curve (AUCs) were 0.809, 0.814, and 0.812 for cCLIA, sCLIA, and LC-MS/MS, respectively, with no statistically significant differences among the methods. A DRC cutoff of 8.1 mU/L was used to define low-DRC (≤8.1 mU/L) and high-DRC (>8.1 mU/L) subgroups. In the low-DRC subgroup, AUCs were 0.880, 0.879, and 0.881; in the high-DRC subgroup, they were 0.871, 0.878, and 0.859, respectively. Optimism-corrected AUCs remained close to the original estimates. Method-specific high-sensitivity and high-specificity thresholds were used to construct an exploratory DRC-stratified interpretive strategy.

CLIA-based 24-h UEA measurements showed strong correlation and small mean bias with LC-MS/MS and similar diagnostic discrimination in this cohort. DRC stratification may support method-specific interpretation of 24-h UEA, but the proposed thresholds require prospective external validation before clinical implementation.