Aldosterone:Renin Ratio

Serum (refrigerated) and plasma (frozen)

1 mL serum and 1 mL plasma

0.5 mL serum and 0.8 mL plasma (Note: This volume does not allow for repeat testing.)

Red-top tube or gel-barrier tube and lavender-top (EDTA) tube

Patients should be instructed to maintain an unrestricted dietary salt intake prior to testing. Washout of all interfering antihypertensive medications may be considered in patients with mild hypertension but is potentially problematic in others and perhaps unnecessary in that medications with minimal effect on the ARR can be used in their place. The patient should not take drugs that markedly affect the ARR for at least four weeks prior to blood collection. These drugs include:

• Spironolactone, eplerenone, amiloride, and triamterene

• Potassium-wasting diuretics

• Products derived from licorice root (e.g., confectionary licorice, chewing tobacco)

More details can be found in the Endocrine Society clinical practice guideline.¹

Screening test for primary aldosteronism in higher risk groups of hypertensive patients

A number of factors can affect the aldosterone:renin ratio and thus lead to false-positive or false-negative results.¹ These include:

Factors producing falsely decreased ARR (false negative)

• Potassium-wasting diuretics

• Potassium-sparing diuretics

• Angiotensin-converting enzyme (ACE) inhibitors

• Angiotensin II type 1 receptor blockers (ARBs)

• Calcium blockers, dihydropyridines (DHPs)

• Hypokalemia

• Sodium restricted

• Pregnancy

• Renovascular hypertension

• Malignant hypertension

Factors producing falsely increased ARR (false positive)

• β-adrenergic blockers

• Central α₂-agonists (e.g., clonidine, α-methyldopa)

• Nonsteroidal anti-inflammatory drugs (NSAIDs)

• Renin inhibitors

• Potassium loading

• Sodium loaded

• Advancing age

• Renal impairment

• Pseudohypoaldosteronism type 2

The ARR should be regarded as a detection test only and should be repeated if the initial results are inconclusive or difficult to interpret because of suboptimal sampling conditions (e.g., maintenance of some medications listed above). The consensus guideline recommended that patients with a positive ARR should proceed to confirmatory testing by any of four confirmatory tests.¹

Liquid chromatography/tandem mass spectrometry (LC/MS-MS)

0.0−30.0 ng/dL per ng/mL/hour

The Clinical Guidelines Subcommittee of the Endocrine Society has produced a practice guideline for the detection, diagnosis, and treatment of patients with primary aldosteronism (PA).¹ Primary aldosteronism (PA) is defined as a group of disorders in which aldosterone production is inappropriately high, relatively autonomous, and nonsuppressible by sodium loading.¹ This inappropriate production of aldosterone can result in cardiovascular damage, suppression of plasma renin, hypertension, sodium retention, and potassium excretion that can lead to hypokalemia. PA is commonly caused by an adrenal adenoma, by unilateral or bilateral adrenal hyperplasia, or, in rare cases, by the inherited condition of glucocorticoid-remediable aldosteronism (GRA).

In the past, clinical guidelines indicated that hypokalemia was required for the diagnosis of PA. As a result, PA was considered to be a relatively uncommon cause of hypertension, accounting for <1% of cases;^2,3 however, more recent studies have challenged these assumptions. Cross-sectional and prospective studies report PA in >10% of hypertensive patients, both in general and in specialty settings.^4-12 Only a small subset of these patients with PA (9% to 37%) had hypokalemia.¹³ These studies indicate that normokalemic hypertension constitutes the most common presentation of the disease, with hypokalemia probably present in only the more severe cases. In fact, the presence of hypokalemia has low sensitivity and specificity, and a low positive predictive value for the diagnosis of PA.¹

The new consensus guideline¹ recommends that case detection of primary aldosteronism (PA) should be undertaken in patient groups with relatively high prevalence of PA. These include patients with:

• Joint National Commission (JNC) stage 2 (>160−179/100−109 mmHg), or stage 3 (>180/110 mmHg) hypertension

• Drug-resistant hypertension

• Hypertension and spontaneous or diuretic-induced hypokalemia

• Hypertension with adrenal incidentaloma

• Hypertension and a family history of early-onset hypertension or cerebrovascular accident at a young age (<40 years).

The new consensus guideline¹ also recommends case detection for all hypertensive first-degree relatives of patients with PA. The consensus group went on to recommend the use of the plasma aldosterone:renin ratio (ARR) to detect cases of PA in these patient groups.^14-20 The ARR is calculated as the ratio of the serum aldosterone (in ng/dL) divided by serum plasma renin activity (in ng/mL/hour). The guideline indicates that the diagnosis of PA provides the opportunity for health benefits provided by curative approaches including surgery or improved control of hypertension through specific medical treatment.

The consensus guideline recommended that patients with a positive ARR should proceed to confirmatory testing by any of four confirmatory tests described within the document and listed below to definitively confirm or exclude the diagnosis.¹

1. Oral sodium loading

2. Saline infusion

3. Fludrocortisone suppression

4. Captopril challenge

Refer to the consensus document for a more detailed description of the confirmatory test.¹