Diagnostic Accuracy of the Aldosterone–to–Active Renin Ratio for Detecting Primary Aldosteronism

Stefan Pilz; Martin H. Keppel; Christian Trummer; Verena Theiler-Schwetz; Marlene Pandis; Valentin Borzan; Matthias Pittrof; Barbara Obermayer-Pietsch; Martin R. Grübler; Nicolas Verheyen; Vinzenz Stepan; Andreas Meinitzer; Jakob Voelkl; Winfried März; Andreas Tomaschitz

Disclosures

J Endo Soc. 2019;3(9):1748-1758. 

In This Article

Abstract and Introduction

Abstract

Context: The aldosterone–to–active renin ratio (AARR) is the recommended screening test for primary aldosteronism (PA), but prospective study data on its sensitivity and specificity are sparse.

Objective: To investigate the diagnostic accuracy of the AARR for detecting PA.

Design: Prospective diagnostic accuracy study.

Setting: This study was conducted from February 2009 to August 2015 at the outpatient clinic of the Department of Endocrinology and Diabetology of the Medical University of Graz, Austria.

Participants: Four hundred patients with arterial hypertension who were referred to a tertiary care center for screening for endocrine hypertension.

Intervention: Participants had a determination of the AARR (index test) and a second AARR determination followed by a saline infusion test (SIT) after 2 to 6 weeks. PA was diagnosed in individuals with any AARR ≥3.7 ng/dL/μU/mL [including a plasma aldosterone concentration (PAC) of ≥9 ng/dL] who had a PAC ≥10 ng/dL after the SIT. We did not substantially alter antihypertensive drug intake.

Main Outcome Measures: Primary outcome was the receiver-operating characteristic (ROC) curve of the AARR in diagnosing PA.

Results: A total of 382 participants were eligible for analyses; PA was diagnosed in 18 (4.7%) patients. The area under the ROC curve of the AARR in detecting PA was 0.973 (95% CI, 0.956 to 0.990). Sensitivity and specificity for a positive AARR in diagnosing PA were 100% (95% CI, 81.5% to 100.0%) and 89.6% (95% CI, 86.0% to 92.5%), respectively.

Conclusions: The AARR has good diagnostic accuracy for detecting PA.

Introduction

Primary aldosteronism (PA) affects approximately 5% to 10% of patients with arterial hypertension and is associated with an excess risk of morbidity and mortality when compared with essential hypertension.[1–3] Therefore, the Endocrine Society clinical practice guideline for the management of PA recommends wide screening for PA in ~50% of patients with arterial hypertension, including patients with resistant hypertension or hypokalemia.[1] Real-life data, however, show that screening for PA is rarely performed, and PA remains an underdiagnosed and undertreated disease.[3]

The recommended screening test for PA is determination of the aldosterone-to-renin ratio because it reflects the degree of aldosterone synthesis that is autonomous with regard to renin.[1,4] Measuring and interpreting the aldosterone-to-renin ratio is, however, a challenge because several factors affect aldosterone and renin concentrations.[5,6] Moreover, few prospective studies have evaluated the diagnostic accuracy of the aldosterone-to-renin ratio in detecting PA. Several previous studies in this field were limited by, for example, a missing prespecified statistical analysis plan, restricting confirmatory tests for PA to participants with a positive screening test result (and thus risk of verification bias), or incomplete adherence to guidelines for study reporting.[7–16] In many of those studies, common antihypertensive drugs were discontinued for the purpose of PA diagnostics, an approach that may limit the implementation of such procedures into routine clinical care. Hence, diagnostic accuracy studies on the aldosterone-to-renin ratio in detecting PA are still needed.

Herein we present the results of the prospective Graz Endocrine Causes of Hypertension (GECOH) study, a diagnostic accuracy study with the primary aim of evaluating the sensitivity and specificity of the aldosterone–to–active renin ratio (AARR) in detecting PA.[17,18]

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