Comparative analysis of aldosterone and renin assays for primary aldosteronism screening

Figures

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  Fig. 1. Passing-Bablok regression analysis for plasma aldosterone concentration (PAC) (A,C,E) and Bland–Altman analysis (B,D,F), along with comparisons of PAC measurements from identical samples over the full measurement range (G) and in screening samples only (H) (values from the same sample are connected by lines). Values from chemiluminescent enzyme immunoassay (CLEIA) and liquid chromatography/mass spectrometry/mass spectrometry (LC–MS/MS) were highly correlated and nearly identical. In contrast, radioimmunoassay (RIA) values were higher than both CLEIA and LC–MS/MS values. Differences between groups were evaluated using Friedman’s test followed by Dunn’s multiple comparisons test. “Screening”, “loading test”, “AVS”, and “95% LoA” refer to screening, loading test, adrenal venous sampling samples, and 95% limits of agreement, respectively.

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  Fig. 2. Passing-Bablok regression analysis for renin measurements over the entire range (A,E,G) and in the low plasma renin activity (PRA) range (B,F,H), in addition to comparisons of PRA measurements from identical samples over the full measurement range (G) and in radioimmunoassay (RIA) values < 2 ng/mL/h (D) (values from the same samples are connected by a line). PRA values from enzyme immunoassay (EIA) were significantly higher than PRA_RIA values. Correlations between PRA and active renin concentration (ARC) values were relatively low, complicating accurate conversion. Notably, in the low-renin range, a broad range of ARC values corresponded to each PRA value, allowing for a more granular assessment of renin values. Inter-group differences were evaluated using Wilcoxon matched-pairs signed rank tests. “Screening,” “loading test”, and “AVS” signify screening, loading test, and adrenal venous sampling samples, respectively.

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  Fig. 3. Distribution of plasma aldosterone concentration (PAC) and plasma renin activity (PRA) in the primary aldosteronism (PA) and non-PA groups according to different aldosterone-to-renin ratio (ARR) methods (A–C) and derivation of ARR cutoff values using receiver operating characteristic curve analysis (D–I). For all PAC assay methods, PAC/PRA_ radioimmunoassay (RIA) was significantly higher in the PA group than in the non-PA group. Cutoff values and specificity are shown, with sensitivity set at 80.6%. The area under the curve (AUC) was greater for the ARR using PAC determined by chemiluminescent enzyme immunoassay (CLEIA) than for the ARR using PAC determined by RIA. Inter-group differences were evaluated using the Mann‒Whitney U test. The letter “a” represents specificity and an ARR threshold at 90.3% sensitivity; “b” represents specificity and an ARR threshold at 80.6% sensitivity; “c” represents sensitivity, specificity, and an ARR threshold at the Youden Index.

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  Fig. 4. Waterfall plots evaluating the concordance of aldosterone-to-renin ratios (ARRs) measured by different plasma aldosterone concentration (PAC) assays between primary aldosteronism (PA) and non-PA groups. (A,C,E). ARRs shown on the left y-axis are plotted on the x-axis from left to right in descending order, and the corresponding ARRs on the right y-axis are aligned at the same x-coordinate. Cutoff values for each ARR at a sensitivity of 80.6% are indicated on both the left and right y-axes. (B,D,F) Enlarged views of the dotted line areas in A, C, and E, respectively. Dots in the pink false-positive (FP) zone indicate false positives for ARRs on the right y-axis. The ARRs using PAC values determined by radioimmunoassay (RIA) resulted in more false positives than the ARRs using PAC values determined by chemiluminescent enzyme immunoassay (CLEIA). Units for all y-axis values are ng/dL/ng/mL/h.