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Aldosterone-Renin Ratio

0070073

Aldosterone/Renin Activity Ratio 0070073

Method

Quantitative Chemiluminescent Immunoassay (CLIA)/Quantitative Enzyme-Linked Immunosorbent Assay (ELISA)

Initial test for primary aldosteronism
Test includes direct measurement of aldosterone and measurement of renin activity
Aldosterone-renin ratio is determined by calculation

3005949

Aldosterone and Renin Direct, With Ratio 3005949

Method

Qualitative Chemiluminescent Immunoassay (CLIA)

Initial test for primary aldosteronism
Test includes direct measurement of aldosterone and renin
Aldosterone-renin ratio is determined by calculation

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 concentrations. Renin concentrations 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 accounted for when interpreting results.

For more information about the diagnosis and management of aldosteronism, refer to the Endocrine Society guideline.

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 not drestrict 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 necessary to control hypertension prior to ARR measurement, begin use of another antihypertensive medication with lesser effects on ARR:
  - Verapamil slow release (a nondihydropyridine slow-release antagonist calcium channel)
  - Hydralazine (a vasodilator)
  - Prazosin hydrochloride (an α-adrenergic blocker)
  - Doxazosin mesylate (an α-adrenergic blocker)
  - Terazosin hydrochloride (an α-adrenergic blocker)
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.
- Withdrawal of oral contraceptives is not required; aldosterone-renin activity ratio should be considered when oral contraceptives or hormone replacement therapy are in use.

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 Plasma Aldosterone Concentrations	Effect on Renin Concentrations	Effect on ARR	Potential False Result
Medications
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, ovulating individuals^a	↔ or ↑	↓	↑	False positive^b
Other Conditions
Malignant hypertension	↑	↑ ↑	↓	False negative
Pregnancy	↑	↑ ↑	↓	False negative
Pseudohypoaldosteronism type 2	↔	↓	↑	False positive
Renal impairment	↔	↓	↑	False positive
Renovascular hypertension	↑	↑ ↑	↓	False negative
^aIn premenopausal, ovulating women, plasma aldosterone concentration is similar to that of men (and renin concentrations are lower) in all phases except the luteal phase. ARR is generally higher in women than in men, and it increases even further during the luteal phase. ^bIf possible, screening during the follicular phase may reduce the likelihood of false positives. When screening during the luteal phase, renin should be measured as PRA (rather than DRC) to avoid false positives. ↔, normal; ↑, increased; ↓, decreased; ↑ ↑, more significant increase; ↓ ↓, more significant decrease; ACE, angiotensin-converting enzyme; DRC, direct renin concentration; PRA, plasma renin activity Source: Funder, 2016

Results

Result	ARR	ARR	Clinical Interpretation^a
	Aldosterone/Renin Activity Ratio 0070073	Aldosterone and Renin Direct, With Ratio 3005949
Positive	>25^b	>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 (3005949) 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

26934393

Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916.

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