What is the aldosterone-to-renin ratio and how is it used to screen for primary aldosteronism?

Aldosterone-to-Renin Ratio (ARR) for Primary Aldosteronism Screening

The aldosterone-to-renin ratio (ARR) is the most accurate and reliable screening test for primary aldosteronism, with a commonly used cutoff of 30 (when aldosterone is in ng/dL and renin activity in ng/mL/h), but requires plasma aldosterone ≥10 ng/dL to be considered positive. 1

What is the ARR?

The ARR is a calculated ratio comparing plasma aldosterone concentration to plasma renin activity (PRA) or direct renin concentration (DRC). It serves as the first-line screening tool for primary aldosteronism (PA) because it demonstrates:

• Higher sensitivity (68-94%) compared to measuring serum potassium, plasma aldosterone, or urinary aldosterone alone 2
• Lower variability related to environmental conditions like potassium levels, sodium load, age, and posture 2
• Negative predictive value approaching 100% for ruling out PA, particularly for aldosterone-producing adenomas 2

Standardized Testing Conditions

Critical requirements for accurate ARR measurement 1, 2:

• Timing: Morning collection, >2 hours after awakening
• Position: Sitting for 5-15 minutes before blood draw
• Diet: Unrestricted (normal) salt intake
• Potassium: Must be in normal range (hypokalemia falsely lowers aldosterone)
• Medication withdrawal:
  • Mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks 1
  • Ideally avoid beta-blockers and clonidine (suppress renin, causing false positives)
  • ACE inhibitors and ARBs can continue (may actually improve diagnostic accuracy) 3

Interpretation Thresholds

The 2018 ACC/AHA guideline recommends 1:

• ARR cutoff: >30 (when aldosterone in ng/dL, PRA in ng/mL/h)
• Minimum aldosterone: ≥10 ng/dL (to avoid false positives from very low renin)

Alternative thresholds from international consensus 4:

• ARR screening only applied if aldosterone >240 pmol/L (9 ng/dL)
• Very low renin values corrected: DRC <5 mIU/L set to 5 mIU/L; PRA <0.2 ng/mL/h set to 0.2 ng/mL/h
• When aldosterone >550 pmol/L (20 ng/dL) on ≥2 measurements with low renin: PA confirmed without further testing 4
• When aldosterone <240 pmol/L (9 ng/dL) on 2 measurements: PA ruled out 4

Who Should Be Screened?

The 2025 Endocrine Society guideline now recommends universal screening in ALL hypertensive patients 5, representing a major shift from prior risk-based approaches.

High-priority populations (where PA prevalence is 11-30%) 1, 5:

• Resistant hypertension (11-29%)
• Hypertension with spontaneous or diuretic-induced hypokalemia (28%)
• Hypertension with adrenal incidentaloma
• Early-onset hypertension (<40 years; prevalence 16%)
• Family history of early-onset hypertension or stroke at young age
• Grade 2-3 hypertension (10-22% prevalence)

Common Pitfalls

Aldosterone levels are often NOT dramatically elevated 6:

• 67% of PA patients had aldosterone <30 ng/dL
• 45% had aldosterone <20 ng/dL
• Suppressed renin is the key diagnostic feature, not necessarily high aldosterone

ARR has intrinsic variability 4:

• Aldosterone shows pulsatile secretion
• Repeat testing is mandatory if results don't match clinical picture
• In one study, 31-39% of surgically confirmed PA cases had normal ARR on at least one measurement 4

Sensitivity varies widely in practice 7:

• Meta-analysis showed ARR sensitivity ranging from 10-100%
• Three studies reported sensitivity <50%
• This reflects differences in populations, thresholds, and assay methods

Confirmatory Testing Algorithm

After positive ARR screening 1, 4:

1. If aldosterone >550 pmol/L (20 ng/dL) on ≥2 measurements with suppressed renin: PA confirmed, proceed to subtyping 4

2. If ARR elevated but aldosterone 240-550 pmol/L (9-20 ng/dL): Perform confirmatory test 1, 4:

   • IV saline suppression test (2L over 4 hours; failure to suppress aldosterone <280 pmol/L confirms PA)
   • Oral salt loading (300 mmol/day × 3 days; failure to suppress <240 pmol/L confirms PA)
   • Fludrocortisone suppression test
   • Captopril suppression test

3. If confirmed PA and surgery considered: Adrenal venous sampling to determine unilateral vs bilateral disease 1

Treatment Implications

Why accurate diagnosis matters for morbidity/mortality 1:

• Unilateral disease (50% of PA): Laparoscopic adrenalectomy improves BP in 100%, cures hypertension in ~50%
• Bilateral disease (50% of PA): Mineralocorticoid receptor antagonists (spironolactone or eplerenone) as first-line
• Both treatments: Effectively lower BP, reverse left ventricular hypertrophy, and reduce cardiovascular risk beyond BP control alone

The ARR remains the best available screening tool despite limitations, but clinicians must recognize its variable performance and the critical importance of proper testing conditions and repeat measurements when clinical suspicion remains high.