Aldosterone:Renin Ratio

CPT: 82088; 84244
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Test Details

Synonyms

  • ARR

Test Includes

Aldosterone, plasma renin activity (PRA)

Use

Screening test for primary aldosteronism in higher risk groups of hypertensive patients

Limitations

A number of factors can affect the aldosterone:renin ratio and thus lead to false-positive or false-negative results.1 These include:

Factors producing falsely increased ARR (false negative)

• Potassium-wasting diuretics

• Potassium-sparing diuretics

• Angiotensin-converting enzyme (ACE) inhibitors

• Angiotensin II type 1 receptor blockers (ARBs)

• Calcium blockers, dihydropyridines (DHPs)

• Hypokalemia

• Sodium restricted

• Pregnancy

• Renovascular hypertension

• Malignant hypertension

Factors producing falsely increased ARR (false positive)

• β-adrenergic blockers

• Central α2-agonists (eg, clonidine, α-methyldopa)

• Nonsteroidal anti-inflammatory drugs (NSAIDs)

• Renin inhibitors

• Potassium loading

• Sodium loaded

• Advancing age

• Renal impairment

• Pseudohypoaldosteronism type 2

The ARR should be regarded as a detection test only, and should be repeated if the initial results are inconclusive or difficult to interpret because of suboptimal sampling conditions (eg, maintenance of some medications listed above). The consensus guideline recommended that patients with a positive ARR should proceed to confirmatory testing by any of four confirmatory tests.1

Methodology

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

Reference Interval

0−30 ng/dL per ng/mL/hour

Additional Information

The Clinical Guidelines Subcommittee of the Endocrine Society has produced a practice guideline for the detection, diagnosis, and treatment of patients with primary aldosteronism (PA).1 Primary aldosteronism (PA) is defined as a group of disorders in which aldosterone production is inappropriately high, relatively autonomous, and nonsuppressible by sodium loading.1 This inappropriate production of aldosterone can result in cardiovascular damage, suppression of plasma renin, hypertension, sodium retention, and potassium excretion that can lead to hypokalemia. PA is commonly caused by an adrenal adenoma, by unilateral or bilateral adrenal hyperplasia, or, in rare cases, by the inherited condition of glucocorticoid-remediable aldosteronism (GRA).

In the past, clinical guidelines indicated that hypokalemia was required for the diagnosis of PA. As a result, PA was considered to be a relatively uncommon cause of hypertension, accounting for <1% of cases;2,3 however, more recent studies have challenged these assumptions. Cross-sectional and prospective studies report PA in >10% of hypertensive patients, both in general and in specialty settings.4-12 Only a small subset of these patients with PA (9% to 37%) had hypokalemia.13 These studies indicate that normokalemic hypertension constitutes the most common presentation of the disease, with hypokalemia probably present in only the more severe cases. In fact, the presence of hypokalemia has low sensitivity and specificity, and a low positive predictive value for the diagnosis of PA.1

The new consensus guideline1 recommends that case detection of primary aldosteronism (PA) should be undertaken in patient groups with relatively high prevalence of PA. These include patients with:

• Joint National Commission (JNC) stage 2 (>160−179/100−109 mmHg), or stage 3 (>180/110 mmHg) hypertension

• Drug-resistant hypertension

• Hypertension and spontaneous or diuretic-induced hypokalemia

• Hypertension with adrenal incidentaloma

• Hypertension and a family history of early-onset hypertension or cerebrovascular accident at a young age (<40 years).

The new consensus guideline1 also recommends case detection for all hypertensive first-degree relatives of patients with PA. The consensus group went on to recommend the use of the plasma aldosterone:renin ratio (ARR) to detect cases of PA in these patient groups.14-20 The ARR is calculated as the ratio of the serum aldosterone (in ng/dL) divided by serum plasma renin activity (in ng/mL/hour). The guideline indicates that the diagnosis of PA provides the opportunity for health benefits provided by curative approaches including surgery or improved control of hypertension through specific medical treatment.

The consensus guideline recommended that patients with a positive ARR should proceed to confirmatory testing by any of four confirmatory tests described within the document and listed below to definitively confirm or exclude the diagnosis.1

1. Oral sodium loading

2. Saline infusion

3. Fludrocortisone suppression

4. Captopril challenge

Refer to the consensus document for a more detailed description of the confirmatory test.1

Specimen Requirements

Specimen

Serum (refrigerated) and plasma (frozen)

Volume

1 mL serum and 1 mL plasma

Minimum Volume

0.5 mL serum and 0.8 mL plasma (Note: This volume does not allow for repeat testing.)

Container

Red-top tube or gel-barrier tube and lavender-top (EDTA) tube

Patient Preparation

Patients should be instructed to maintain an unrestricted dietary salt intake prior to testing. Washout of all interfering antihypertensive medications may be considered in patients with mild hypertension, but is potentially problematic in others and perhaps unnecessary in that medications with minimal effect on the ARR can be used in their place. The patient should not take drugs that markedly affect the ARR for at least four weeks prior to blood collection. These drugs include:• Spironolactone, eplerenone, amiloride, and triamterene• Potassium-wasting diuretics• Products derived from liquorice root (eg, confectionary licorice, chewing tobacco)More details can be found in the Endocrine Society clinical practice guideline.1

Collection

Collect blood mid morning, after the patient has been up (sitting, standing, or walking) for at least two hours and seated for 5 to 15 minutes. Refer to descriptions for individual tests Renin Activity, Plasma [002006] and Aldosterone, LC/MS [004374] for more detailed preparation and test collection information. After collection, immediately centrifuge the lavender-top tube at room temperature, transfer plasma to a transport tube, and freeze. Label this tube "Frozen Plasma−Renin." If a red-top tube is used, transfer separated serum to a plastic transport tube. Label the serum tube "Serum−Aldosterone." To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.

Storage Instructions

Serum, refrigerated and plasma, frozen

Clinical Information

Footnotes

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(9):3266-3281. 18552288
2. Tucker RM, Labarthe DR. Frequency of surgical treatment for hypertension in adults at the Mayo Clinic from 1973 through 1975. Mayo Clin Proc. 1977; 52(9):549-555. 895197
3. Sinclair AM, Isles CG, Brown I, et al. Secondary hypertension in a blood pressure clinic. Arch Inter Med. 1987; 147(7):1289-1293. 3606286
4. Fardella CE, Mosso L, Gómez-Sánchez C, et al. Primary hyperaldosteronism in essential hypertensives: Prevalence, biochemical profile, and molecular biology. J Clin Endocrinol Metab. 2000; 85(5):1863-1867. 10843166
5. Gordon RD, Stowasser M, Tunny TJ, et al. High incidence of primary aldosteronism in 199 patients referred with hypertension. Clin Exp Pharmacol Physiol. 1994; 21(4):315-318. 7923898
6. Grim CE, Weinberger MH, Higgins JT, et al. Diagnosis of secondary forms of hypertension. A comprehensive protocol. JAMA. 1977; 237(13):1331-1335. 576478
7. Hamlet SM, Tunny TJ, Woodland E, et al. Is aldosterone/renin ratio useful to screen a hypertensive population for primary aldosteronism? Clin Exp Pharmacol Physiol. 1985; 12(3):249-252. 3896593
8. Lim PO, Dow E, Brennan G, et al. High prevalence of primary aldosteronism in the Tayside Hypertension Clinic population. J Hum Hypertens. 2000; 14(5):311-315. 10822317
9. Loh KC, Koay ES, Khaw MC, et al. Prevalence of primary aldosteronism among Asian hypertensive patients in Singapore. J Clin Endocinol Metab. 2000; 85(8):2854-2859. 10946893
10. Mosso L, Carvajal C, González A, et al. Primary aldosteronism and hypertensive disease. Hypertension. 2003; 42(2):161-165. 12796282
11. Rossi GP, Bernini G, Caliumi C, et al. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006; 48(11):2293-2300. 17161262
12. Schwartz GL, Turner ST. Screening for primary aldosteronism In essential hypertension: Diagnostic accuracy of the ratio of plasma aldosterone concentration to plasma renin activity. Clin Chem. 2005; 51(2):386-394. 15681560
13. Mulatero P, Stowasser M, Loh KC, et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. 2004; 89(3):1045-1050. 15001583
14. Rossi GP, Bernini G, Desideri G, et al. Renal damage in primary aldosteronism: Results of the PAPY study. Hypertension. 2006; 48(2):232-238. 16801482
15. Hiramatsu K, Yamada T, Yukimura Y, et al. A screening test to identify aldosterone-producing adenoma by measuring plasma renin activity. Results in hypertensive patients. Arch Intern Med. 1981; 141(12):1589-1593. 7030245
16. McKenna TJ, Sequeria SJ, Heffernan A, et al. Diagnosis under random conditions of all disorders of the renin-angiotensin-aldosterone axis, including primary hyperaldosteronism. J Clin Endocrinol Metab. 1991; 73(5):952-957. 1939533
17. Stowasser M, Gordon RD, Gunasekera TG, et al. High rate of detection of primary aldosteronism, including surgically treatable forms, after "non-selective" screening of hypertensive patients. J Hypertens. 2003; 21(11):2149-2157. 14597859
18. Gordon RD. Primary aldosteronism. J Endocrinol Invest. 1995; 18(7):495-511. 9221268
19. Stowasser M, Gordon RD. The aldosterone-renin ratio for screening for primary aldosteronism. The Endocrinologist. 2004; 14:267-276.
20. Tanabe A, Naruse M, Takagi S, et al. Variability in the renin/aldosterone profile under random and standardized sampling conditions in primary aldosteronism. J Clin Endocrinol Metab. 2003; 88(6):2489-2494. 12788844

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
004354 Aldosterone/Renin Ratio 55151-5 004371 Aldosterone ng/dL 1763-2
004354 Aldosterone/Renin Ratio 55151-5 002006 Renin Activity, Plasma ng/mL/hr 2915-7
004354 Aldosterone/Renin Ratio 55151-5 004356 Aldos/Renin Ratio 30894-0
Reflex Table for Aldosterone
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 123246 Disclaimer: 123246 Disclaimer: N/A

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