FeedbackQuantitative Chemiluminescent Immunoassay/Quantitative Enzyme-Linked Immunosorbent Assay
- Use to screen and diagnose aldosteronism
- Test includes direct measurement of aldosterone and measure of renin activity; aldosterone-renin ratio is determined by calculation
Quantitative Chemiluminescent Immunoassay
- 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
- At least 4 weeks before collection, withdraw agents that may have a significant effect on ARR:
- 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
| 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 |
||||
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
-
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.