Qualitative Chemiluminescent Immunoassay (CLIA)
- Initial test for primary aldosteronism
- Test includes direct measurement of aldosterone and renin
- Aldosterone-renin ratio is determined by calculation
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
Primary aldosteronism occurs when aldosterone production is inappropriately high in relation to the patient’s sodium status, which causes cardiovascular damage, hypertension, sodium retention, and suppression of plasma renin. An increase in potassium excretion can occur that can lead to hypokalemia (low blood potassium levels). 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. A variety of factors may need to be considered when interpreting ARR results.
Disease Overview
Diagnostic and Prognostic Considerations
It is now recommended that all individuals with hypertension be screened for primary aldosteronism. This may be accomplished by measuring aldosterone and renin and calculating the aldosterone-renin ratio. The results of this testing inform clinical care, allowing decision-making regarding surgical treatment (when indicated) or medical therapy. A significant associated finding can be adrenocortical carcinoma, often identified by an initial computed tomography (CT) scan for exploratory assessment and subtype assignment. Primary aldosteronism can be unilateral or bilateral, determined by bilateral adrenal venous sampling, allowing decision-making regarding medical therapy, including surgery.
A diagnosis of primary aldosteronism is associated with a significantly higher risk of cardiovascular events compared with essential hypertension, even after adjustment for age, sex, and blood pressure. Targeted treatment is of clear benefit, and the identification of patients with primary aldosteronism should be an important public health objective. For more information about the diagnosis and management of aldosteronism, refer to the Endocrine Society guideline.
Genetics
Patients who have onset of primary aldosteronism before 20 years of age, or who have a family history of primary aldosteronism or stroke before 40 years of age, should undergo genetic testing for familial hyperaldosteronism type 1 (FH-I). Patients with early-onset primary aldosteronism should be considered for germline genetic testing for variants in KCNJ5, which cause familial hyperaldosteronism type 3 (FH-III).
Testing Protocol
The ARR should be considered a detection test only, as false-positive and false-negative results are possible. Refer to Interpretive Factors to Consider for information about the effect of different variables on the ARR. Repeat testing should be performed if initial results are inconclusive or uninterpretable, or in the case of a negative result when primary aldosteronism is strongly suspected.
Accurate ARR testing requires careful attention to patient preparation, timing of sample collection, and additional sample collection conditions and requirements. Detailed considerations and steps for sample collection and testing are linked in the ARUP Laboratory Test Directory under Aldosterone/Renin Activity Ratio 0070073 and Aldosterone and Renin Direct, With Ratio 3005949, as well as in the Endocrine Society clinical practice guideline. For additional information about laboratory testing for primary aldosteronism, refer to the ARUP Primary Aldosteronism Testing Algorithm.
Test Interpretation
Interpretive Factors to Consider
For more information, refer to the Factors Affecting ARR Results table.
- Patient age: At 65 years of age or older, patients can have raised ARR due to a greater decrease in renin than aldosterone with age.
- Sex: In females who are ovulating or premenstrual, ARR levels are higher than for age-matched males when renin is measured as direct renin concentration (DRC) (not applicable for plasma renin activity [PRA]).
- Time of day, posture, length of time in posture, and recent dietary intake
- Medication use or exposure
- Method used for blood collection, considering any challenges or difficulties with collection
- Potassium levels in blood
- Creatinine levels in blood (Renal failure can cause false-positive results.)
| Factor | Effect on Plasma Aldosterone Concentrations | Effect on Renin Concentrations | Effect on ARR | Potential False Result |
|---|---|---|---|---|
| Medications | ||||
| ACE inhibitors | Decreased | Significantly increased | Decreased | False negative |
| Angiotensin II type 1 receptor blockers | Decreased | Significantly increased | Decreased | False negative |
| β-adrenergic blockers | Decreased | Significantly decreased | Increased | False positive |
| Ca2+ blockers (dihydropyridine) | Normal or increased | Increased | Decreased | False negative |
| Central alpha-2 agonists (e.g., clonidine, α-methyldopa) | Decreased | Significantly decreased | Increased | False positive |
| Nonsteroidal anti-inflammatory drugs | Decreased | Significantly decreased | Increased | False positive |
| Potassium-sparing diuretics | Increased | Significantly increased | Decreased | False negative |
| Potassium-wasting diuretics | Normal or decreased | Significantly increased | Decreased | False negative |
| Renin inhibitors | Decreased | Decreased (PRA) Increased (DRC) | Increased (PRA) Decreased (DRC) | False positive (PRA) False negative (DRC) |
| Electrolyte Status | ||||
| Hypokalemia | Decreased | Normal or increased | Decreased | False negative |
| Potassium loaded | Increased | Normal or Decreased | Increased | — |
| Sodium loaded | Decreased | Significantly decreased | Increased | False positive |
| Sodium restricted | Increased | Significantly increased | Increased | False negative |
| Demographic Characteristics | ||||
| Age >65 years | Decreased | Significantly decreased | Increased | False positive |
| Premenopausal, ovulating individualsa | Normal or Increased | Decreased | Increased | False positiveb |
| Other Conditions | ||||
| Malignant hypertension | Increased | Significantly increased | Decreased | False negative |
| Pregnancy | Increased | Significantly increased | Decreased | False negative |
| Pseudohypoaldosteronism type 2 | Normal | Decreased | Increased | False positive |
| Renal impairment | Normal | Decreased | Increased | False positive |
| Renovascular hypertension | Increased | Significantly increased | Decreased | 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 further during the luteal phase. bIf possible, screening during the follicular phase may reduce the likelihood of false-positive results. When screening during the luteal phase, renin should be measured as PRA (rather than DRC) to avoid false positives. ACE, angiotensin-converting enzyme | ||||
Results Interpretation
| Result | ARR (Aldosterone/Renin Activity Ratio 0070073) | ARR (Aldosterone and Renin Direct, With Ratio 3005949) | Clinical Interpretationa |
|---|---|---|---|
| Positive | >25b | >3.7 | Suggestive of hyperaldosteronism; requires confirmation |
| Negative | ≤25 | ≤3.7 | Primary aldosteronism unlikely |
aRefer to Factors Affecting ARR Results table. bIf aldosterone concentration is >15 ng/dL. | |||
Limitations
- Reference intervals for serum aldosterone are based on normal sodium intake.
- Reference intervals for aldosterone are dependent on whether patient is upright or supine at blood draw.
- 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
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40658480
Adler GK, Stowasser M, Correa RR, et al. Primary aldosteronism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2025;110(9):2453-2495.
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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.

