How do you interpret renin and aldosterone (Angiotensin-Converting Enzyme) lab results?

How to Interpret Renin and Aldosterone Labs

Primary Purpose: Screening for Primary Aldosteronism

The aldosterone-to-renin ratio (ARR) is the recommended screening test for primary aldosteronism, calculated by dividing plasma aldosterone concentration (ng/dL) by plasma renin activity (ng/mL/h), with a positive screen defined as ARR ≥30 AND plasma aldosterone ≥10 ng/dL. 1, 2

When to Order These Tests

Screen patients with any of the following high-risk features:

• Resistant hypertension (BP uncontrolled on 3 medications including a diuretic) 1, 2
• Severe hypertension (BP >180/110 mmHg) 1, 2
• Hypokalemia (spontaneous or diuretic-induced), though notably absent in 50% of primary aldosteronism cases 2
• Incidentally discovered adrenal mass 2
• Family history of early-onset hypertension or stroke at age <40 years 2

Primary aldosteronism affects up to 20% of patients with resistant hypertension and up to 12% of those with severe hypertension, yet screening rates remain dismally low at only 2-4% of eligible patients. 1, 2

Patient Preparation: Critical for Accurate Interpretation

Medication Management

Two approaches exist, and you must choose based on clinical context:

Approach 1 (Pragmatic): Test patients on their current medications and interpret results in context of those medications. 1 This reduces barriers to screening and avoids dangerous BP fluctuations in poorly controlled patients. 1

Approach 2 (Ideal): Discontinue interfering medications when clinically feasible:

• Stop these drugs (they suppress renin and cause false-positives): Beta-blockers, centrally acting drugs (clonidine, methyldopa), and diuretics 1, 3
• Use these instead: Long-acting calcium channel blockers (dihydropyridine or non-dihydropyridine) and alpha-receptor antagonists minimally interfere with ARR 1, 2
• Caution with ACE inhibitors/ARBs: These elevate renin and can cause false-negatives 4, 3, 5

Beta-blockers increase ARR by 62% on average, potentially causing false-positives, while ACE inhibitors and ARBs decrease ARR by 30-43%, risking false-negatives. 3, 5

Other Preparation Requirements

• Correct hypokalemia first - it suppresses aldosterone production and causes false-negatives 2, 4
• Ensure unrestricted salt intake - sodium status affects interpretation 1, 2
• Timing matters: Collect blood in the morning after patient has been out of bed for 2 hours and seated for 5-15 minutes 2

Interpreting the Results

Pattern 1: High Aldosterone, Low Renin (High ARR)

This suggests primary aldosteronism when ARR ≥30 AND aldosterone ≥10 ng/dL. 1, 2

Critical caveat: The ARR has significant limitations. Research shows sensitivity of only 22-66% and specificity of 67-99% depending on the population and medications. 6, 5 The test becomes increasingly unreliable as ARR values rise due to marked variability. 7

Next steps:

1. Confirmatory testing is mandatory - never diagnose based on ARR alone 1, 2
2. Options include:
   • IV saline suppression test (2L normal saline over 4 hours; failure to suppress aldosterone <5 ng/dL confirms diagnosis) 2
   • Oral salt loading with 24-hour urine aldosterone measurement 1, 2
3. Refer to endocrinology or hypertension specialist for confirmatory testing and subtype determination 2, 4

Pattern 2: High Aldosterone, High Renin (Normal or Low ARR)

This suggests secondary hyperaldosteronism, most commonly from renovascular hypertension. 4

Evaluate for:

• Renal artery stenosis using renal artery duplex ultrasound or CT angiography 4
• Clinical clues: Flash pulmonary edema, asymmetric kidney size, severe/refractory hypertension 4
• Medication effects: Diuretics, ACE inhibitors, ARBs, and beta-blockers all elevate renin 4

Management: Medical therapy is first-line for atherosclerotic renal artery stenosis, as revascularization shows no benefit over medical management in most cases. 4 Consider revascularization only for refractory hypertension despite optimal medical therapy, progressive renal decline, flash pulmonary edema, or fibromuscular dysplasia. 4

Pattern 3: Low Aldosterone, High Renin

This pattern is not consistent with primary aldosteronism and suggests volume depletion, diuretic use, or other causes of secondary hyperreninemia. 1

Pattern 4: Low Aldosterone, Low Renin

Consider adrenal insufficiency or other causes of hypoaldosteronism in the appropriate clinical context.

Common Pitfalls to Avoid

• Don't rely on hypokalemia - it's absent in 50% of primary aldosteronism cases 2
• Don't skip confirmatory testing - ARR alone has poor reproducibility with up to 5-fold variation between measurements taken under identical conditions 7, 5
• Don't proceed to surgery based on CT findings alone - adrenal venous sampling is mandatory before adrenalectomy, as CT leads to inappropriate surgery in 25% of cases 2, 4
• Don't forget mineralocorticoid receptor antagonists - withdraw at least 4 weeks before testing 1, 2
• Don't interpret isolated high ARR as diagnostic - in 36% of cases, elevated ARR reflects low renin alone without truly elevated aldosterone 6

Units and Cut-offs

ARR cut-offs vary by laboratory and units used. 1 The standard cut-off of ≥30 applies when aldosterone is measured in ng/dL and renin activity in ng/mL/h. 2 Some sources use alternative cut-offs (≥20 or different units), so always verify your local laboratory's reference ranges. 2, 6