The aldosterone to renin ratio in the diagnosis of primary aldosteronism: Promises and challenges

The complexity of evaluating patients for secondary treatable causes of hypertension is underappreciated. Primary aldosteronism (PA) is the most prevalent cause of secondary hypertension (3%‐32% of hypertensive patients). The recent endocrine society clinical practice guideline (ESCPG), “The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment”, differs from the previous version in the explicit recognition of PA as a major public health issue. Despite this, PA is underdiagnosed. The guidelines call on physicians to substantially ramp up the screening of hypertensive patients at risk of PA. Further, it recommends the plasma aldosterone to renin ratio (ARR), as the test of choice for screening for PA. However, the ARR is a highly variable test with reported diagnostic sensitivities and specificities ranging from 66% to 100% and 61% to 100%, respectively. Variability of the ARR can be attributed to the high degree of within‐subject variation, differences in sampling protocols, laboratory assays, reporting units, the effect of medications and the population characteristics used to establish the decision thresholds. These factors render the possibility of false positive and false negative results—which have the potential to adversely impact patients. The limitations and caveats to the use of the ARR necessitate an effective clinic‐laboratory interface, with specialist physician and clinical scientist collaboration for ARR result interpretation. Improvement in the diagnostic sensitivity and specificity of the ARR is predicated on harmonisation of pretesting patient preparation criteria, knowledge of the analytical methods used to derive the ratio and the method‐specific threshold for PA.