Big Data Approach to Assessment of an Aldosterone-Renin Ratio for Detection of Potential Surgical Cases of Primary Aldosteronism

BACKGROUND: Prior retrospective studies of aldosterone-renin ratio (ARR) measures were confounded by selection bias. METHODS: To define ARR sensitivity independent of case definition, administrative health and diagnostic imaging repositories in Alberta, Canada, were used to construct a 5-component definition for primary aldosteronism (PA) for the most easily recognizable cases. Components included hypertension, hypokalemia, adrenal mass, suppressed renin, and nonsuppressed aldosterone. ARR was omitted from the definition, permitting independent evaluation of the ARR using receiver operating characteristic curve analysis. The definition was validated by adrenal vein sampling and surgical outcomes. RESULTS: Of 931 adrenal vein sampling patients, 19.2% met the 5-component PA case definition; of these, 86.8% had unilateral disease, and of the 76.8% who underwent surgery, 91.2% achieved complete biochemical response. Between 2012 and 2019, 6717 patients with hypertension had ARR measured; 60.9% had computed tomography or magnetic resonance imaging performed for any reason. The prevalence of the 5-component PA cases was 4.8% by direct renin concentration and 6.6% by plasma renin activity. The area under the receiver operating characteristic curve for the ARR was 0.84 (0.81-0.86) and 0.82 (0.78-0.85) when direct renin concentration and plasma renin activity were used. The 90% sensitivity ARR threshold for the 5-component PA case definition was 26 pmol/mIU (direct renin) and 350 pmol/ng per mL/h (renin activity), with specificities of 60% and 56%. At 5% prevalence rates, positive predictive values were 11% and 10%. Commonly recommended ARR screening thresholds of 70 pmol/mIU or 550 pmol/ng per mL/h had sensitivities of 68% and 82%, respectively, for a surgically relevant PA phenotype. CONCLUSIONS: Current ARR thresholds have low-to-moderate sensitivity for cases of PA where adrenal vein sampling and surgery are strong considerations.