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Aldosterone/Plasma Renin Activity Ratio, LC/MS/MS

Aldosterone/Plasma Renin Activity Ratio, LC/MS/MS

Test Summary

Aldosterone/Plasma Renin Activity Ratio, LC/MS/MS

Clinical Use

  • Screen for primary aldosteronism

Clinical Background

Primary aldosteronism (PA) is characterized by hypertension and an inappropriately high aldosterone concentration that cannot be suppressed by sodium loading. Additionally, patients may have low plasma renin activity, an increased blood level of sodium, and, in more severe cases, a decreased potassium blood level. Underlying causes include adrenal adenoma, unilateral or bilateral adrenal hyperplasia, inherited hypertension syndromes, and rarely, adrenal carcinoma. PA has been diagnosed in >10% of patients with hypertension.1 Available treatments, including surgery and mineralocorticoid receptor antagonists, are effective in reducing cardiovascular and cerebrovascular damage.

The Endocrine Society recommends PA screening of high-risk hypertensive patients using the aldosterone to renin ratio (ARR) (Figure).1 The ARR is more sensitive than potassium, and aldosterone measurements are more specific than renin measurements. If the ARR is elevated, 1 of 4 tests can be used to confirm the diagnosis: oral sodium loading, saline infusion, fludrocortisone suppression, or a captopril challenge.1

Figure. Diagnosis and Management of Primary Aldosteronism (PA)

Individuals Suitable for Testing

Individuals suitable for testing include those with1:

  • Drug-resistant hypertension (>140/>90 mm Hg despite treatment with 3 medications)

  • Moderate to severe hypertension (>160-179/100-109 mm Hg or >180/110 mm Hg)

  • Hypertension and spontaneous or diuretic-induced hypokalemia

  • Hypertension with adrenal incidentaloma

  • Hypertension and a family history of hypertension or cerebrovascular accident before age 40 years

  • Hypertension and a first-degree relative with PA

Ideally, collect samples in the morning after the patient has been out of bed for ≥2 hours and after sitting 5-15 minutes. Dietary salt intake should not be restricted, and potassium should be normalized if possible. The following medications have minimal effect on aldosterone to renin ratio (ARR), so patients can continue therapy during screening and follow-up testing: verapamil slow release, hydralazine, prazosin hydrochloride, doxazosin mesylate, and terazosin hydrochloride. Additional information regarding medications and patient preparation can be found in the Endocrine Society guidelines.1



  • Liquid chromatography tandem mass spectrometry (LC/MS/MS)

  • Analytical sensitivity: 1.0 ng/dL

  • Analytical specificity: no known interferences

Plasma renin activity (PRA):

  • Angiotensin I generation and LC/MS/MS2

  • Quality control includes detection of peptidase degradation of angiotensin I for each sample (to improve accuracy)

  • Analytical sensitivity: 0.03 ng/mL/h

  • Analytical specificity: no known interferences

Interpretive Information

Increased ARR is associated with PA, hereditary glucocorticoid-remediable aldosteronism, pseudohypoaldosteronism type 2, certain medications (Table), potassium or sodium loading, very low PRA levels, renal failure, and a patient age >65 years.1 Decreased ARR is associated with pregnancy, renovascular hypertension, malignant hypertension, certain medications (Table), sodium restriction, and hypokalemia.1

Table. Impact of Medications on the Aldosterone/Renin Ratio (ARR)1
False-positive ARR False-negative ARR
β-Adrenergic blockers Potassium-wasting or -sparing diuretics
Central α2 agonists (eg, clonidine, α-methyldopa) ACE inhibitors
NSAIDs Angiotensin II type 1 receptor blockers
Renin inhibitors Calcium blockers (eg, dihydropyridine)

NSAIDs, nonsteroidal anti-inflammatory drugs; ACE, angiotensin-converting enzyme.

ARR results should be interpreted in light of the patient’s age, sample collection conditions (eg, time of day, posture and length of time in that posture, sodium and potassium status, and medications being taken), as well as the patient’s clinical history.


  1. Funder JW, Carey RM, Fardella C, et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93:3266-3281.

  2. Bystrom CE, Salameh W, Reitz R, Clarke NJ. Plasma renin activity by LC-MS/MS: development of a prototypical clinical assay reveals a subpopulation of human plasma samples with substantial peptidase activity. Clin Chem. 2010;56:1561-1569.

Content reviewed 11/2014

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