What is the aldosterone‑renin ratio, what threshold indicates primary aldosteronism, and how should the test be prepared and interpreted?

Aldosterone-Renin Ratio (ARR) for Primary Aldosteronism Screening

What is the Aldosterone-Renin Ratio?

The aldosterone-renin ratio (ARR) is calculated by dividing plasma aldosterone concentration (ng/dL) by plasma renin activity (ng/mL/h), and serves as the standard screening test for primary aldosteronism in hypertensive patients. 1

• ARR = Plasma Aldosterone Concentration (ng/dL) ÷ Plasma Renin Activity (ng/mL/h) 1
• Plasma renin activity (PRA) is preferred over direct renin concentration (DRC) for calculating ARR because PRA is more widely used in international guidelines and most studies 2

Diagnostic Threshold for Primary Aldosteronism

A positive screening test requires BOTH an ARR ≥20-30 AND a plasma aldosterone concentration ≥10-15 ng/dL. 1

• The American College of Cardiology reports that an ARR of 20 ng/dL per ng/mL/hr has excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism 1
• Most guidelines recommend an ARR cutoff of ≥30 when aldosterone is measured in ng/dL and renin activity in ng/mL/h 1
• The specificity improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 1
• The absolute aldosterone level must be at least 10-15 ng/dL in addition to the elevated ratio to interpret the test as positive 1

Important caveat: Recent research shows ARR sensitivity varies widely (10-100%) depending on the population and diagnostic criteria used, with three studies reporting sensitivity <50% 3. The test's reproducibility is also poor, with Bland-Altman plots showing almost five-fold differences in ARR values taken under identical conditions 4. This underscores why confirmatory testing is mandatory after any positive ARR screening result 1.

Patient Preparation Before Testing

Medication Management

Ideally, interfering medications should be substituted or discontinued when clinically appropriate, though testing can proceed on current medications if discontinuation is unsafe. 1

Medications to STOP (when feasible):

• Beta-blockers should be stopped 2-5 days before testing—they suppress renin and cause false-positive ARR 1, 5
• Diuretics should be discontinued when possible—they increase renin and cause false-negative ARR 1, 5
• Mineralocorticoid receptor antagonists (spironolactone, eplerenone) must be withdrawn at least 4 weeks before testing 1, 6
• ACE inhibitors and ARBs should be stopped at least 2 weeks before testing—they increase renin and cause false-negative ARR 1, 4
• Centrally acting drugs (clonidine, alpha-methyldopa) can cause false positives 5

Safe alternatives to use during washout:

• Long-acting calcium channel blockers (amlodipine, verapamil slow-release) minimally interfere with ARR and can be continued 1, 5
• Alpha-receptor antagonists (prazosin, doxazosin, hydralazine) are acceptable alternatives 1

If medications cannot be stopped: Interpret results in the context of the specific medications the patient is taking 1. Research shows that under random medication (particularly ACE inhibitors and ARBs), ARR sensitivity drops to 22.2% but specificity remains 98.7% 4.

Metabolic Preparation

Patients must be potassium-replete before testing, as hypokalemia suppresses aldosterone production and causes false-negative results. 1

• Target serum potassium 4.0-5.0 mEq/L 1
• Hypokalemia is present in only 50% of primary aldosteronism cases, so normal potassium does not exclude the diagnosis 1

Ensure unrestricted (liberal) salt intake before testing. 1

• Testing should be performed with normal dietary sodium intake 1
• Salt restriction can suppress aldosterone and cause false-negative results 1

Blood Collection Protocol

Collect blood in the morning (ideally 0800-1000 hours), with the patient out of bed for 2 hours prior to collection and seated for 5-15 minutes immediately before the blood draw. 1

• Blood must be drawn with the patient in a seated position 1
• The 2-hour upright posture requirement is critical for standardization 5

Test Interpretation and Next Steps

When ARR is Positive (≥20-30 with aldosterone ≥10-15 ng/dL)

All positive screening tests require confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed with sodium loading. 1

Confirmatory test options include: 1

• Intravenous saline suppression test: Infuse 2L of normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms the diagnosis 1
• Oral sodium loading test with 24-hour urine aldosterone measurement 1
• Fludrocortisone suppression test 1

After confirmatory testing is positive:

• Refer all patients to a hypertension specialist or endocrinologist for subtype determination 1
• Obtain non-contrast CT scan of the adrenal glands as initial imaging 1
• Adrenal venous sampling (AVS) is mandatory before offering adrenalectomy to distinguish unilateral from bilateral disease, except in patients <40 years when imaging shows a single affected gland 1, 6

Who Should Be Screened

Screen all patients with: 1

• Resistant hypertension (BP not controlled on 3 medications including a diuretic)—prevalence of primary aldosteronism is up to 20% 1
• Severe hypertension (BP >180/110 mmHg)—prevalence up to 12% 1
• Spontaneous or diuretic-induced hypokalemia 1
• Adrenal incidentaloma discovered on imaging 1
• Family history of early-onset hypertension or stroke at age <40 years 1
• Young-onset hypertension (<30-40 years) without traditional risk factors 1

Common Pitfalls to Avoid

• Never rely on hypokalemia alone to trigger screening—it is absent in approximately 50% of primary aldosteronism cases 1
• Never proceed to surgery based on CT findings alone—up to 25% of patients might undergo unnecessary adrenalectomy without adrenal venous sampling 1
• Never perform confirmatory testing in patients actively taking mineralocorticoid receptor antagonists—they must be withdrawn for at least 4 weeks 1, 6
• Never skip confirmatory testing after a positive ARR—the screening test alone has poor specificity due to common low-renin states from volume expansion or dietary salt 1
• Recognize that only 2-4% of eligible patients currently get screened—primary aldosteronism remains markedly underdiagnosed despite being present in 5-10% of all hypertensive patients 1, 6

Clinical Significance

Primary aldosteronism causes dramatically worse cardiovascular outcomes than essential hypertension at equivalent blood pressure levels: 1

• 3.7-fold increase in heart failure
• 4.2-fold increase in stroke
• 6.5-fold increase in myocardial infarction
• 12.1-fold increase in atrial fibrillation

Early diagnosis and targeted treatment—either unilateral adrenalectomy for surgically amenable disease or mineralocorticoid receptor antagonist therapy for bilateral disease—can reverse aldosterone-mediated target-organ damage and mitigate this excess cardiovascular risk. 1