When should an aldosterone (aldosterone) renin ratio be tested in a patient with suspected primary aldosteronism?

When to Test Aldosterone-Renin Ratio

Screen all patients with resistant hypertension (blood pressure uncontrolled on 3 medications including a diuretic) using the aldosterone-renin ratio, as primary aldosteronism is present in up to 20% of these individuals. 1

High-Risk Populations Requiring ARR Testing

The aldosterone-renin ratio should be obtained in the following clinical scenarios:

• Resistant hypertension - Blood pressure not controlled on 3 antihypertensive medications including a diuretic 1
• Severe hypertension - Blood pressure >180/110 mmHg 1
• Hypertension with hypokalemia - Either spontaneous or diuretic-induced 1, 2
• Incidentally discovered adrenal mass on CT or MRI in a hypertensive patient 1, 2
• Family history of early-onset hypertension or stroke at age <40 years 1, 2
• Well-controlled hypertension with a first-degree relative who has primary aldosteronism 2
• Hypertension with atrial fibrillation 2
• Hypertension with obstructive sleep apnea 2

Critical Screening Context

A common pitfall is relying on hypokalemia as a trigger for testing - hypokalemia is absent in the majority (approximately 50%) of primary aldosteronism cases, so normal potassium levels should never exclude consideration of screening. 1, 3

Only 2-4% of eligible high-risk patients currently undergo screening, representing a major gap in diagnosis. 1 Given that primary aldosteronism affects approximately 6% of all hypertensive patients in primary care and up to 20% of those with resistant hypertension, systematic screening of high-risk groups is essential. 2, 1

Patient Preparation Before Testing

Potassium Repletion

• Ensure the patient is potassium-replete before testing, as hypokalemia suppresses aldosterone production and can cause false-negative results 1

Medication Management

• Stop when feasible: Beta-blockers, centrally acting drugs (clonidine, methyldopa), and diuretics should be discontinued as they suppress renin and cause false-positive results 1, 4
• Safe alternatives: Long-acting calcium channel blockers and alpha-receptor antagonists minimally interfere with ARR and can be used during testing 1
• If medications cannot be stopped: Proceed with testing and interpret results in the context of the specific medications the patient is taking 1, 5
• Mandatory withdrawal: Mineralocorticoid receptor antagonists (spironolactone, eplerenone) must be withdrawn at least 4 weeks before testing 1

Collection Conditions

• Draw blood in the morning after the patient has been out of bed for 2 hours 1
• Patient should be seated for 5-15 minutes immediately before blood collection 1
• Ensure unrestricted salt intake before testing 1

Test Interpretation

A positive screening test requires both of the following criteria:

• ARR ≥30 (when aldosterone measured in ng/dL and renin activity in ng/mL/h) 1, 4
• Plasma aldosterone concentration ≥10-15 ng/dL 1, 4

The specificity improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations. 1, 4

Next Steps After Positive Screening

• All positive ARR tests require confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed with sodium loading 1
• Confirmatory options include intravenous saline suppression test or oral sodium loading with 24-hour urine aldosterone measurement 1
• After biochemical confirmation, refer to a hypertension specialist or endocrinologist for subtype determination with adrenal CT imaging and potentially adrenal venous sampling 1, 3