What is a normal renin (renal hormone)-aldosterone (mineralocorticoid hormone) ratio for evaluating secondary hypertension causes?

Normal Renin-Aldosterone Ratio for Secondary Hypertension Evaluation

A plasma aldosterone-to-renin ratio (ARR) greater than 20-30 when plasma aldosterone is reported in ng/dL and plasma renin activity in ng/mL/hour, with a plasma aldosterone level ≥15 ng/dL, is considered elevated and suggestive of primary aldosteronism requiring further evaluation. 1

Understanding the Aldosterone-Renin Ratio (ARR)

The ARR is the recommended screening test for primary aldosteronism, which is one of the most common causes of secondary hypertension. When interpreting ARR results, several key factors must be considered:

Normal vs. Abnormal Values

• Normal ARR: Generally below 20-30 (when aldosterone is in ng/dL and renin activity in ng/mL/hour)
• Abnormal ARR: ≥20-30 with plasma aldosterone ≥15 ng/dL 1
• Some guidelines suggest an ARR cutoff of ≥20 with plasma aldosterone ≥10 ng/dL 2

Interpretation Considerations

• The ARR has high negative predictive value but low specificity for primary aldosteronism 1
• Low specificity reflects the common occurrence of low-renin hypertension in resistant hypertension patients 1
• The ratio is strongly and inversely dependent on plasma renin activity (PRA) 3

Proper Collection and Testing Conditions

For accurate ARR assessment:

• Collect blood in the morning (preferably between 8-10 AM) 2
• Patient should be seated for 5-15 minutes before collection 2
• Ensure patient is potassium-replete (hypokalemia can affect results) 1
• Normal serum potassium levels are essential for accurate interpretation 1
• Consider collecting at least two ARR measurements due to significant intra-individual variability 4

Medication Effects on ARR

Certain medications significantly affect ARR results:

• Beta-blockers: Increase ARR (by 62% on average) and may cause false positives 5
• ACE inhibitors/ARBs: Decrease ARR (by 30-43%) and may cause false negatives 5
• Calcium channel blockers: Minimal effect (decrease by approximately 17%) 5
• Alpha-blockers (e.g., doxazosin): Minimal effect (decrease by approximately 5%) 5
• Mineralocorticoid receptor antagonists: Should be discontinued before testing 2

When to Screen for Primary Aldosteronism

ARR screening is recommended in patients with:

• Resistant hypertension (BP above goal despite optimal doses of ≥3 agents) 1
• Hypokalemia (spontaneous or substantial diuretic-induced) 1
• Incidentally discovered adrenal mass 1
• Family history of early-onset hypertension 1, 2
• Stroke at a young age 1
• Age under 40 with hypertension 2

Confirming Primary Aldosteronism

If ARR screening is positive:

1. Confirm with additional testing (e.g., fludrocortisone suppression test, saline infusion test) 1
2. Refer to a hypertension specialist or endocrinologist for further evaluation 1
3. Proceed to imaging studies only after biochemical confirmation 1, 2

Common Pitfalls in ARR Interpretation

• False negatives: Can occur with ARB treatment (up to 23.5% false negative rate) 5
• False positives: Common with beta-blocker treatment 5
• Variability: Significant intra-individual variability exists (coefficient of variation 41-42%) 4
• Low renin states: Can elevate ARR without true primary aldosteronism 3
• Position changes: Moving from supine to seated position can increase the ratio 3
• Diuretic therapy: Can decrease the ratio despite increasing renin 3

By understanding these factors, clinicians can appropriately interpret ARR results and identify patients who require further evaluation for primary aldosteronism, a potentially curable cause of hypertension.