Aldosterone-Renin Ratio

  • Use to screen and diagnose aldosteronism
  • Test includes direct measurement of aldosterone and measure of renin activity; aldosterone-renin ratio is determined by calculation
  • Use to screen and diagnose aldosteronism
  • Test includes direct measurement of aldosterone and renin; aldosterone-renin ratio is determined by calculation

For more aldosterone and renin tests, see Related Tests

Primary aldosteronism occurs when aldosterone production is inappropriately high in relation to the patient’s sodium status which causes cardiovascular damage, hypertension, and retention. Aldosterone-renin ratio (ARR) is the most reliable method for screening for primary aldosteronism. ARR is determined by measuring both aldosterone and renin levels. Renin levels may be determined by measuring direct renin concentrations or renin activity. ARR testing requires specific procedures to properly prepare for specimen collection. Additionally, a variety of factors must be taken into account for proper test interpretation.

For more information about the diagnosis and management of aldosteronism, see the Endocrine Society Guidelines. 

Testing Protocol

Patient Preparation

  • Make attempt to correct hypokalemia; when measuring plasma potassium make sure to:
    • Collect blood using syringe and needle
    • Avoid fist clenching during collection
    • Wait ≥5 seconds after tourniquet release to achieve needle insertion
    • Ensure that plasma separates from cells within 30 minutes of collection
  • Encourage patient to liberalize and not restrict sodium intake
  • Withdraw interfering agents
    • At least 4 weeks before collection, withdraw agents that may have a significant effect on ARR:
      • Triamterene, amiloride, eplerenone, and spironolactone
      • Potassium-wasting diuretics
      • Any products developed from licorice root (eg, chewing tobacco, licorice)
    • If results are inconclusive after withdrawing above agents, withdraw agents with a less significant effect on ARR at least 2 weeks before collection:
      • Nonsteroidal anti-inflammatory drugs, central α-2 agonists, β-adrenergic blockers
      • Renin inhibitors, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and dihydropyridine calcium channel antagonists
      • If hypertension must be controlled, consider treating with slow-release verapamil, hydralazine, prazosin hydrochloride, doxazosin mesylate, and terazosin hydrochloride
  • Establish whether patient is taking oral contraceptives or receiving hormone replacement therapy because estrogen can result in a false-positive when using direct renin measurement for ARR

Conditions for Blood Collection

  • If measuring renin activity, collect midmorning after patient has been out of bed ≥2 hours and after patient has been seated 5-15 minutes. 
  • If measuring direct renin, collect midmorning (7-10 a.m.) after patient has been out of bed ≥30 minutes; if taking an upright sample, patient should be seated for 5-15 minutes; if taking a supine sample, patient should be in the supine position for ≥30 minutes.
  • Collect blood carefully and avoid stasis and hemolysis during collection 
  • Maintain sample at room temperature (not on ice) during both transport to laboratory and before centrifugation and rapid freezing of the plasma component pending assay 

Test Interpretation

Interpretive Factors to Consider

Factors Affecting ARR Results
Factor Effect on Aldosterone Plasma Levels Effect on Renin Levels Effect on ARR Potential False Result

Medicationsa

ACE inhibitors

↑ ↑

False negative

Angiotensin II type 1 receptor blockers

↑ ↑

False negative

β-adrenergic blockers

↓ ↓

False positive

Ca2+ blockers (dihydropyridine)

↔ or ↓

False negative

Central alpha-2 agonists (eg, clonidine, α-methyldopa)

↓ ↓

False positive

Nonsteroidal anti-inflammatory drugs

↓ ↓

False positive

Potassium-sparing diuretics

↑ ↑

False negative

Potassium-wasting diuretics

↔ or ↓

↑ ↑

False negative

Renin inhibitors

↓ (PRA)

↑ (DRC)

↑ (PRA)

↓ (DRC)

False positive (PRA)

False negative (DRC)

Electrolyte Status

Hypokalemia

↔ or ↑

False negative

Potassium loaded

↔ or ↓

Sodium loaded

↓ ↓

False positive

Sodium restricted

↑ ↑

False negative

Demographics

Age >65 years

↓ ↓

False positive

Premenopausal adult cisgender femalesb

↔ or ↑

False positiveb

Other Conditions

Malignant hypertension

↑ ↑

False negative

Pregnancy

↑ ↑

False negative

Pseudohypoaldosteronism type 2

False positive

Renal impairment

False positive

Renovascular hypertension

↑ ↑

False negative

aFalse positives can occur during the luteal phase, but only if renin is measured as DRC and not PRA. In preliminary studies, some investigations have found false positives on the current cutoffs for women in the luteal phase. Accordingly, it would seem sensible to screen women at the follicular phase, if practicable.

bIn premenopausal, ovulating women, plasma aldosterone levels measured during the menses or the proliferative phase of the menstrual cycle are similar to those of men but rise briskly in the luteal phase. Because renin levels are lower, the ARR is higher than in men for all phases of the cycle, but especially during the luteal phase, during which aldosterone rises to a greater extent than renin.

↔, normal; ↑, increased; ↓, decreased; ↑ ↑, more significant increase; ↓ ↓, more significant decrease; DRC, direct renin concentration; PAC, plasma aldosterone concentration

Source: Funder, 2016 

Results

Result ARR ARR Clinical Interpretationa
  Aldosterone/Renin Activity Ratio 0070073 Aldosterone and Renin, Direct with Ratio 2002582  
Positive >25b >3.7 Suggestive of hyperaldosteronism; requires confirmation
Negative ≤25 ≤3.7 Primary aldosteronism unlikely

aSee Factors Affecting ARR Results table.

bIf aldosterone concentration is >15 ng/dL.

Limitations

  • Reference intervals for serum aldosterone are based on normal sodium intake.
  • Aldosterone and Renin, Direct with Ratio (2002582) should not be used for patients being treated with cathepsin B.
  • Aldosterone/Renin Activity Ratio (0070073) is preferred for menstruating females and those taking medications containing estrogen.

References