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.

Feasibility of Screening Primary Aldosteronism by Aldosterone-to-Direct Renin Concentration Ratio Derived from Chemiluminescent Immunoassay Measurement: Diagnostic Accuracy and Cutoff Value

“…According to Endocrine Society guidelines published in 2016 [4], ARR was still recommended as the method of choice for screening PA, despite the emerging evidence obtained with ADRR. The reason for this might be that the accurate cutoff value of ADRR is still controversial [4, 17, 18]. Therefore, ADRR has not been widely used in daily clinical practice [1].…”

Recent Development toward the Next Clinical Practice of Primary Aldosteronism: A Literature Review

“…Based on the biochemical features of PA, including autonomous overproduction of aldosterone and subsequent renin suppression, screening for PA is performed with evaluation of both PAC and renin levels and its ratio. For renin measurement, plasma renin activity has been widely used in practice for a long time, while recently, direct renin concentration has come to the fore due to the more rapid and reproducible ability [ 93 , 94 ]. The measurement of plasma aldosterone has also gradually transited from radioimmunoassay to mass spectrometry for the reliability [ 95 , 96 ].…”

Parameters of captopril challenge test can predict results of other confirmatory tests for primary aldosteronism and propose the next test to be done

“…The serum certified reference material of aldosterone (NMIJ CRM 6402) was established in 2016 [19], and the JES issued the operational guidelines that recommended manufacturers to make measurement results of each aldosterone assay kit metrologically traceable to SI unit using this primary reference material in 2018. For the SPAC-S Aldosterone RIA kit, the traceability to the primary reference material has not been established, and PAC values measured by this kit were reportedly different from those measured by the liquid chromatography tandem mass spectrometry [20]. However, the SPAC-S Aldosterone RIA kit was the standard kit to measure PAC values in the JES PA guidelines in 2009 [10], and the majority of evidence, on which Japanese guidelines relied [9,10,21], was established on PAC values measured by this kit.…”