What is aldosterone‑renin ratio (ARR) screening when evaluating secondary hypertension?

ARR Screening for Secondary Hypertension

The aldosterone-to-renin ratio (ARR) is the recommended screening test for primary aldosteronism—the most common and potentially curable cause of secondary hypertension—performed by measuring plasma aldosterone and renin simultaneously in the morning after the patient has been seated for 5-15 minutes. 1, 2

What ARR Screening Detects

Primary aldosteronism is far more prevalent than historically recognized, affecting approximately 5-10% of all hypertensive patients and up to 20% of those with resistant hypertension. 1, 2 This condition carries dramatically higher cardiovascular risk than essential hypertension at equivalent blood pressure levels, including:

• 12.1-fold increase in atrial fibrillation 2
• 6.5-fold increase in myocardial infarction 2
• 4.2-fold increase in stroke 2
• 3.7-fold increase in heart failure 2

Despite these alarming statistics, screening rates remain dismally low—only 2-4% of eligible patients are actually tested. 1

Who Should Be Screened

You should order ARR screening in any patient with: 1, 2

• Resistant hypertension (BP uncontrolled on ≥3 medications including a diuretic)
• Severe hypertension (BP >180/110 mmHg)
• Spontaneous or diuretic-induced hypokalemia (though 50% of primary aldosteronism cases have normal potassium) 1, 2
• Adrenal incidentaloma on imaging 2
• Family history of early-onset hypertension or stroke before age 40 2
• Young-onset hypertension (<30-40 years without traditional risk factors) 2

How to Perform ARR Testing

Patient Preparation

Correct hypokalemia first—target serum potassium 4.0-5.0 mEq/L, as hypokalemia suppresses aldosterone production and causes false-negative results. 2, 3

Medication management presents two valid approaches: 1

1. Test on current medications and interpret results in context (reduces barriers to screening, avoids BP deterioration) 1
2. Optimize medications before testing for a "clean" screen 1

If withdrawing interfering medications: 1, 2

• Stop mineralocorticoid receptor antagonists (spironolactone, eplerenone) ≥4 weeks before testing 2, 3
• Stop beta-blockers, centrally acting drugs (clonidine, methyldopa), and diuretics when feasible 1, 3
• Continue long-acting calcium channel blockers (like amlodipine) and alpha-receptor antagonists—they minimally interfere with ARR 1, 3

Blood Collection Protocol

Collect blood in the morning (ideally 0800-1000 hours) with the patient: 2

• Out of bed for ≥2 hours prior to collection 2
• Seated for 5-15 minutes immediately before blood draw 2
• On unrestricted (liberal) salt intake 2

Interpreting ARR Results

A positive screening test requires BOTH: 2

• ARR ≥20-30 (when aldosterone measured in ng/dL and renin activity in ng/mL/h) 2
• Plasma aldosterone concentration ≥10-15 ng/dL 2

Specificity improves if minimum plasma renin activity of 0.5 ng/mL/h is used in calculations. 2

The ARR can be calculated using either plasma renin activity (PRA) or direct renin concentration (DRC), with strong correlation between the two methods (r = 0.92). 4

Critical Next Steps

All positive ARR screening tests require confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed with sodium loading. 1, 2 Options include: 2

• Intravenous saline suppression test (2L normal saline over 4 hours; failure to suppress aldosterone <5 ng/dL confirms diagnosis) 2
• Oral sodium loading test with 24-hour urine aldosterone measurement 2
• Fludrocortisone suppression test 1

After biochemical confirmation, refer all patients to a hypertension specialist or endocrinologist for subtype determination via adrenal venous sampling to distinguish unilateral (surgically curable) from bilateral disease (requiring lifelong medical therapy). 1, 2

Common Pitfalls to Avoid

Never rely on hypokalemia alone—it is absent in approximately 50% of primary aldosteronism cases. 1, 2

Never proceed to surgery based on CT findings alone—up to 25% of patients would undergo unnecessary adrenalectomy without adrenal venous sampling. 2

Never test patients taking mineralocorticoid receptor antagonists without a ≥4-week washout period, as results will be uninterpretable. 2

Recognize that ACE inhibitors and ARBs increase renin (causing false-negative ARR), while beta-blockers and diuretics suppress renin (causing false-positive ARR). 1, 5 If medications cannot be stopped, interpret results accordingly or consider testing a pragmatic approach that accepts these limitations. 1