Quantitative Value of Aldosterone-Renin Ratio for Detection of Aldosterone-Producing Adenoma: The Aldosterone-Renin Ratio for Primary Aldosteronism (AQUARR) Study

Abstract

Background: Current guidelines recommend use of the aldosterone-renin ratio (ARR) for the case detection of primary aldosteronism followed by confirmatory tests to exclude false-positive results from further diagnostic workup. We investigated the hypothesis that this could be unnecessary in patients with a high ARR value if the quantitative information carried by the ARR is taken into due consideration.

Methods and results: We interrogated 2 large data sets of prospectively collected patients studied with the same predefined protocol, which included the captopril challenge test. We used an unambiguous diagnosis of aldosterone-producing adenoma as reference index. We also assessed whether the post-captopril ARR and plasma aldosterone concentration fall furnished a diagnostic gain over baseline ARR values. We found that the false-positive rate fell exponentially, and, conversely, the specificity increased with rising ARR values. At receiver operating characteristics curves and diagnostic odds ratio analysis, the high baseline ARR values implied very high positive likelihood ratio and diagnostic odds ratio values. The baseline and post-captopril ARR showed similar diagnostic accuracy (area under the receiver operating characteristics curve) in both the exploratory and validation cohorts, indicating lack of diagnostic gain with this confirmatory test (between-area under the curve difference, 0.005; 95% CI, -0.031 to 0.040; P=0.7 for comparison, and 0.05; 95% CI, -0.061 to 0.064; P=0.051 for comparison, respectively).

Conclusions: These results indicate that the ARR conveys key quantitative information that, if properly used, can simplify the diagnostic workup, resulting in saving of money and resources. This can offer the chance of diagnosis and ensuing adrenalectomy to a larger number of hypertensive patients, ultimately resulting in better control of blood pressure.

Keywords: accuracy; aldosterone; aldosterone‐producing adenoma; aldosterone‐renin ratio; diagnostic method; high blood pressure; hypertension; primary aldosteronism; specificity.

Figure 1

Flow chart of the AQUARR (Aldosterone‐Renin Ratio for Primary Aldosteronism) study. *The accuracy of the aldosterone‐renin ratio (ARR) was determined by analysis of the area under the receiver operating characteristics curve, positive and negative likelihood ratio, diagnostic odds ratio), and error rate. The optimal cut‐off values were established by Youden index analysis. APA indicates aldosterone‐producing adenoma; PA, primary aldosteronism; PAPY, Primary Aldosteronism Prevalence in hYpertension.

Figure 2

Diagnostic yield of the aldosterone‐renin ratio (ARR) values. The plot shows that increasing ARR values are associated with an exponential increase of specificity and an exponential decrease of false negative (FN) rate for identification of aldosterone‐producing adenoma patients in the exploratory (A) and validation (B) cohort. FP indicates false positive.

Figure 3

Receiver operating characteristics (ROC) curve of baseline (BAS) and post‐captopril (Capt) aldosterone‐renin ratio (ARR) for diagnosing aldosterone‐producing adenoma (APA). In both the exploratory (A) and the validation (B) cohort, the area under the curve (AUC) of the baseline and captopril ARR was higher than the 0.500 (eg, the AUC under the identity line). However, the difference between the AUC of the baseline and the post‐captopril ARR was negligible and not statistically significant in both the exploratory (A) and the validation (B) cohort.

Figure 4

The plot of positive likelihood ratio (LRP) and diagnostic odds ratio (DOR) as a function of increasing aldosterone‐renin ratio (ARR) in the validation data set. Please note that raising ARR values are associated with an exponential increase of both LRP and DOR.