Aldosterone, Renin, and Aldosterone-to-Renin Ratio Variability in Screening for Primary Aldosteronism

Context The plasma aldosterone concentration (PAC), renin, and aldosterone-to-renin ratio (ARR) are used to screen for primary aldosteronism (PA). Substantial intra-individual variability of PAC and ARR using plasma renin activity in the context of usual antihypertensive therapy has been described, but there is no data on ARR variability calculated using direct renin concentration (DRC). Objective To describe the intra-individual variability of PAC, DRC, and ARR in the absence of interfering medications in patients with and without PA. Design Retrospective cohort study. Patients Hypertensive patients referred for investigation of PA, with at least 2 ARR measurements while off interfering medications. Setting Endocrine hypertension service of a tertiary center, from May 2017 to July 2021. Main outcome measures PAC, DRC, and ARR variability was calculated as coefficient of variation (CV) and percent difference (PD). Results Analysis of 223 patients (55% female, median age 52 years), including 162 with confirmed PA, demonstrated high variability with a sample CV of 22-25% in the PAC and sample CV of 41% to 42% in the DRC and ARR in both the PA and non-PA groups. The degree of variability was substantially higher than the assays' analytical CV. Sixty-two patients (38%) with PA had at least one ARR below 70 pmol/L:mU/L (2.4 ng/dL:mU/L), a cut-off for first-line screening of PA. Conclusions Significant intra-individual variability in PAC, DRC, and hence ARR occurs in a large proportion of patients being investigated for PA. These findings support the need for at least 2 ARR before PA is excluded or further investigated.

Automated summary

This retrospective cohort study investigated the intra-individual variability of plasma aldosterone concentration (PAC), direct renin concentration (DRC), and aldosterone-to-renin ratio (ARR) in patients with and without primary aldosteronism (PA), without interfering medications. The results demonstrated significant variability in PAC, DRC, and ARR, which was higher than the assays' analytical variability. A substantial proportion of PA patients had ARR values below the cut-off for first-line screening. These findings emphasize the need for multiple ARR measurements in the evaluation of PA.