Rapid Screening of Primary Aldosteronism by a Novel Chemiluminescent Immunoassay

Abstract

Measurement of plasma aldosterone and renin concentration, or activity, is useful for selecting antihypertensive agents and detecting hyperaldosteronism in hypertensive patients. However, it takes several days to get results when measured by radioimmunoassay and development of more rapid assays has been long expected. We have developed chemiluminescent enzyme immunoassays enabling the simultaneous measurement of both aldosterone and renin concentrations in 10 minutes by a fully automated assay using antibody-immobilized magnetic particles with quick aggregation and dispersion. We performed clinical validation of diagnostic ability of this newly developed assay-based screening of 125 patients with primary aldosteronism from 97 patients with essential hypertension. Results of this novel assay significantly correlated with the results of radioimmunoassay (aldosterone, active renin concentration, and renin activity) and liquid chromatography-tandem mass spectrometry (aldosterone). The analytic sensitivity of this particularly novel active renin assay was 0.1 pg/mL, which was better than that of radioimmunoassay (2.0 pg/mL). The ratio of aldosterone-to-renin concentrations of 6.0 (ng/dL per pg/mL) provided 92.0% sensitivity and 76.3% specificity as a cutoff for differentiating primary aldosteronism from essential hypertension. This novel measurement is expected to be a clinically reliable alternative for conventional radioimmunoassay and to provide better throughput and cost effectiveness in diagnosis of hyperaldosteronism from larger numbers of hypertensive patients in clinical settings.

Keywords: aldosterone; diagnosis; human; reaction time; renin.

Figure 1

Correlation of plasma aldosterone concentration (PAC) measurements between chemiluminescent enzyme immunoassay (CLEIA) and radioimmunoassay (RIA; A) and correlation of ARC measurements between CLEIA and immunoradiometric assay (IRMA) (B). ARC indicates active renin concentration.

Figure 2

A, Distribution of chemiluminescent enzyme immunoassay (CLEIA) plasma aldosterone concentration (PAC) measurements in aldosterone-producing adenoma (APA), bilateral hyperaldosteronism (BHA), and essential hypertension (EH). B, Comparison of PAC measurements between CLEIA and RIA. C, Distribution of CLEIA active renin concentration (ARC) measurements in APA, BHA, and EH. D, Comparison of ARC measurements between CLEIA and immunoradiometric assay (IRMA). E, Distribution of ARR_ARC in PA, APA, BHA, and EH.