Renin Activity, Plasma

CPT: 84244 (per specimen)
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Synonyms

  • Plasma Renin Activity (PRA)
  • PRA

Special Instructions

The patient's posture at the time of collection should be noted (see Patient Preparation).


Expected Turnaround Time

4 - 7 days


Related Information


Related Documents


Specimen Requirements


Specimen

Plasma, frozen


Volume

1 mL


Minimum Volume

0.8 mL (Note: This volume does not allow for repeat testing.)


Container

Lavender-top (EDTA) tube


Collection

Draw blood into an EDTA tube. Keep tube at room temperature. Centrifuge at room temperature.1 Transfer the plasma into a LabCorp PP transpak frozen purple tube with screw cap (LabCorp N° 49482). Freeze immediately and maintain frozen until tested. It is critical that the plasma be transferred and frozen as quickly as possible to prevent cryoactivation of protein to renin (which results in falsely elevated renin levels). To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.


Storage Instructions

Freeze


Stability Requirements

Temperature

Period

Room temperature

Unstable

Refrigerated

Unstable

Frozen

14 days

Freeze/thaw cycles

Stable x1


Patient Preparation

In order to facilitate interpretation of test results, the patient should be taken off medications for at least three weeks prior to sample collection (see Limitations for details). Dietary sodium levels during the period prior to testing can affect renin levels. Sodium restriction tends to cause an increase in renin activity, while supplementation can result in lower values. A 24-hour urine sodium determination from a sample collected on the day before a renin test can be used to assess sodium intake.

Since patient posture prior to collection affects renin levels, it is recommended that the patient be ambulatory for at least 30 minutes before blood collection.1 If inpatients are physically able, they should be asked to ambulate for 30 minutes before blood is drawn for renin activity.


Causes for Rejection

Nonfrozen sample received; nonseparated sample received; non-EDTA plasma specimen; gross hemolysis or lipemia


Test Details


Use

Measurement of renin activity is useful in the differential diagnosis of individuals with hypertension. Renin levels will be elevated in patients with hypertension due to renal artery stenosis (ie, renovascular hypertension). Measurement of renin activity can also be useful in the diagnosis of primary aldosteronism. Patients with secondary aldosteronism tend to have low renin levels. Renin can also be used to assess the adequacy of steroid substitution in patients with adrenal insufficiency. Renin activity will be normal in patients with adequate supplementation and will be elevated when steroid substitution is inadequate.


Limitations

This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the Food and Drug Administration.

Transition to upright posture causes a reduction in renal perfusion pressure and an increase in PRA. PRA levels exhibit a diurnal rhythm, with the highest levels observed in the early morning upon awakening and falling during the day.1 Collecting blood for PRA and aldosterone at midmorning from seated patients following a two to four hour upright posture improves the sensitivity of the aldosterone renin (ARR) for primary aldosteronism.2

PRA levels can be increased by dietary salt restriction and suppressed by consumption of a high salt diet.

PRA levels gradually fall as renal function declines with normal aging or with the development of renal impairment due to reduced renin-producing capacity and salt-retention.

A number of drugs can affect the PRA levels.2 These include:

Drugs that tend to increase PRA levels:

• Diuretics (including spironolactone)

• Dihydropyridine calcium channel blockers

• Angiotensin converting enzyme (ACE) inhibitors

• Angiotensin receptor antagonists

Drugs that tend to decrease PRA levels:

• Beta-blockers

• Clonidine

• Alpha-methyldopa

• Nonsteroidal anti-inflammatory agents


Methodology

The renin in plasma is allowed to act on the plasma's endogenous substrate, angiotensinogen producing angiotensin I. This is measured by liquid chromatography/mass spectrometry (LC/MS-MS).


Reference Interval

Age

Range (ng/mL/hr)

0 to 11 m

2.000−37.000

1 to 3 y

1.700−11.200

4 to 5 y

1.000−6.500

6 to 10 y

0.500−5.900

11 to 15 y

0.500−3.300

>15 y

0.167−5.380


Additional Information

Plasma renin activity (PRA) is a measure of the activity of the plasma enzyme renin, which plays a major role in the body's regulation of blood pressure, thirst, and urine output.3,4 Renin produced by the juxtaglomerular apparatus of the kidney converts angiotensinogen to angiotensin I in the plasma. Inactive angiotensin I is further converted to the active octapeptide angiotensin II, a potent vasopressor that is responsible for hypertension of renal origin. Angiotensin II also incites the zona glomerulosa of the adrenal cortex to release aldosterone as part of the renin-angiotensin-aldosterone system (RAS). Renin secretion by the kidney is stimulated by a drop in glomerular blood pressure, by decreased sodium concentration at the distal tubule, or by stimulation of sympathetic outflow to the kidney, as occurs in renal vascular diseases.

Measurement of PRA is most frequently performed in the evaluation of patients with hypertension. Primary Aldosteronism (PA) is a common cause of resistant hypertension and is associated with an increased incidence adverse cardiovascular outcomes.3,5-7 PRA levels are usually diminished in PA, a condition where aldosterone release by the adrenals is not controlled by the renin-angiotensin system and aldosterone production is excessive relative to body's sodium status.3,7-9 The diagnosis of PA is based on measurement of the plasma aldosterone level, PRA, and the calculation of an aldosterone:renin ratio (LabCorp Test number Aldosterone:Renin Ratio [004354]).3,7 Primary aldosteronism can result from an aldosterone-producing adrenocortical tumor (adenoma or, rarely, carcinoma), bilateral adrenal hyperplasia, or glucocorticoid-remediable aldosteronism. Primary aldosteronism is a common cause of hypertension, accounting for as many as 5% to 10% of cases. Most patients with primary aldosteronism do not suffer from hypokalemia.3

PRA levels can be low in patients with forms of congenital adrenal hyperplasia (CAH) that are associated with excessive mineralocorticoid production (ie, 11-beta-hydroxylase or 17-alpha-hydroxylase deficiency). PRA levels can be low in patients with Cushing's syndrome who experience marked elevated cortisol levels. Diminished PRA levels can also be observed in patients with Liddle's syndrome11, congenital or acquired (eg, through ingestion of licorice) deficiency of 11-beta-hydroxysteroid dehydrogenase type 2,12 and in patients with certain mutations of the mineralocorticoid receptor gene.12

PRA levels can be increased in patients with primary adrenal insufficiency, including those with Addison's disease9 with mineralocorticoid activity leads to salt-wasting. These salt-wasting forms of CAH include defects in steroid acute regulatory protein, side-chain cleavage enzyme, 3-beta-hydroxysteroid dehydrogenase, 21-hydroxylase13 or aldosterone synthase.14 PRA levels can be increased in a number of other conditions that are associated with salt wasting including Bartter syndrome, Gitelman syndrome and pseudohypoaldosteronism type I.9 Markedly elevated PRA levels can be seen in patients with reninoma.15 Reninoma is a tumor of the renal juxtaglomerular cell apparatus that causes hypertension and hypokalemia because of the overproduction of renin.15 Reninoma is an uncommon cause of hypertension in a young adult and should be included in the differential diagnosis as a potential life-threatening and curable condition.16,17

PRA is measured in the laboratory by incubating plasma at physiologic temperature in a buffer that facilitates its enzymatic activity. The natural substrate for the enzyme renin is angiotensinogen. Exogenous angiotensinogen is not added to the reaction mixture. This means that, in effect, the PRA results reported are dependent on both renin concentration and the concentration of its substrate in the patient's plasma. Renin cleaves angiotensinogen to produce a decapeptide, angiotensin I, the concentration of which is assayed using liquid chromatography accompanied by tandem mass spectroscopic detection (LC/MS/MS). PRA levels are reported as the amount of angiotensin I generated per unit of time.

PRA measurement is different from direct renin immunoassays that are available from some laboratories.18 Whereas activity assays measure only active renin, immunoassays measure both active and inhibited renin.18 Also, the PRA measurement is affected by endogenous renin substrate (angiotensinogen) levels while the direct renin assays are not. This is important in some populations (eg, women during the luteal phase of menstruation or taking exogenous estrogen) because they tend to have relatively higher levels of renin substrate.19,20 Samples from patients with raised substrate levels and reduced enzyme concentrations produce normal PRA levels. Direct renin levels measured in these patients are lower, resulting in the potential for producing inappropriately elevated aldosterone renin ratios.19,20


Footnotes

1. Hurwitz S, Cohen RJ, Williams GH. Diurnal variation of aldosterone and plasma renin activity: timing relation to melatonin and cortisol and consistency after bed rest. J Appl Physiol (1985). 2004 Apr;96(4):1406-1414.14660513
2. Stowasser M, Ahmed AH, Pimenta E, et al. Factors affecting the aldosterone/renin ratio. Horm Metab Res. 2012 Mar;44(3):170-176.22147655
3. 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 May;101(5):1889-1916.26934393
4. Laragh JH, Sealey JE. The plasma renin test reveals the contribution of body sodium-volume content (V) and renin-angiotensin (R) vasoconstriction to long-term blood pressure. Am J Hypertens. 2011 Nov;24(11):1164-1180.21938070
5. Galati SJ. Primary aldosteronism: Challenges in diagnosis and management. Endocrinol Metab Clin North Am. 2015 Jun;44(2):355-369.26038205
6. Galati SJ, Hopkins SM, Cheesman KC, Zhuk RA, Levine AC. Primary aldosteronism: emerging trends. Trends Endocrinol Metab. 2013 Sep;24(9):421-430.23796656
7. Weiner ID. Endocrine and hypertensive disorders of potassium regulation: Primary aldosteronism. Semin Nephrol. 2013 May;33(3):265-276.23953804
8. Cicala MV, Mantero F. Primary aldosteronism: What consensus for the diagnosis. Best Pract Res Clin Endocrinol Metab. 2010 Dec;24(6):915-921.21115160
9. Van Der Gugten JG, Holmes DT. Quantitation of Plasma Renin Activity in Plasma Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Methods Mol Biol. 2016;1378:243-253.26602136
10. Warnock DG. Liddle syndrome: Genetics and mechanisms of Na+ channel defects. Am J Med Sci. 2001 Dec; 322(6):302-307.11780687
11. Stewart PM. 11 beta-Hydroxysteroid dehydrogenase: Implications for clinical medicine. Clin Endocrinol (Oxf). 1996 May;44(5):493-499.8762725
12. Geller DS, Farhi A, Pinkerton N, et al. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science 2000 Jul 7; 289(5476):119-123.10884226
13. Simpoulos AP, Marshall JR, Delea CS, Bartter FC. Studies on the deficiency of 21-hydroxylation in patients with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1971 Mar; 32(3):438-443.4322392
14. Shizuta Y, Kawamoto T, Mitsuuchi Y, et al. Inborn errors of aldosterone biosynthesis in humans. Steroids. 1995 Jan;60(1):15-21.7792802
15. Wong L, Hsu TH, Perlroth MG, Hofmann LV, Haynes CM, Katznelson L. Reninoma: Case Report and literature review. J Hypertens. 2008 Feb;26(2):368-373.18192852
16. Gottardo F, Cesari M, Morra A, Gardiman M, Fassina A, Dal Bianco M. A kidney tumor in an adolescent with severe hypertension and hypokalemia: An uncommon case--case report and review of the literature on reninoma. Urol Int. 2010;85(1):121-124.20453480
17. Cho MJ, Sung EY, Park JA, Lee HD. Congestive heart failure as an initial manifestation of reninoma. J Pediatr Endocrilol Metab. 2011;24(11-12):1085-1087.22308872
18. Campbell DJ, Nussberger J, Stowasser M, et al. Activity assays and immunoassays for plasma Renin and prorenin: information provided and precautions necessary for accurate measurement. Clin Chem. 2009 May;55(5):867-877.19264850
19. Ahmed AH, Gordon RD, Taylor PJ, Ward G, Pimenta E, Stowasser M. Effect of contraceptives on aldosterone/renin ratio may vary according to the components of contraceptive, renin assay method, and possibly route of administration. J Clin Endocrinol Metab. 2011 Jun;96(6):1797.21411552
20. Ahmed AH, Gordon RD, Taylor PJ, Ward G, Pimenta E, Stowasser M. Are women more at risk of false-positive primary aldosteronism screening and unnecessary suppression testing than men? J Clin Endocrinol Metab. 2011 Feb;96(2):E340-346.20962019

References

Andreoli TE. Disorders of fluid volume, electrolytes, and acid-base balance. In: Wyngaarden JB, Smith LH Jr, eds. Cecil Textbook of Medicine. 18th ed, vol 1. Philadelphia, Pa: WB Saunders Co;1988:528-558.
Demers LM, Whitley RJ. Function of the adrenal cortex. In: Burtis CA, Ashwood ER, eds. Tietz Textbook of Clinical Chemistry. 3rd ed. Philadelphia, Pa: WB Saunders Co;1999:1530-1569.
Laragh JH, Letcher RL, Pickering TG. Renin profiling for diagnosis and treatment of hypertension. JAMA. 1979 Jan 12; 241(2):151-156. 31492
Scammell AM, Diver MJ. Plasma aldosterone and renin activity. Arch Dis Child. 1989 Jan; 64(1):139-141. 2647032
Torres VE, Young WF Jr, Offord KP, Hattery RR. Association of hypokalemia, aldosteronism, and renal cysts. N Engl J Med. 1990 Feb 8; 322(6):345-351. 2405267
Trovati M, Massucco P, Anfossi G, et al. Insulin influences the renin-angiotensin-aldosterone system in humans. Metabolism. 1989 Jun; 38(6):501-503. 2542723
Williams GH, Dluhy RG. Diseases of the adrenal cortex. In: Braunwald E, Isselbacher KJ, Petersdorf RG, et al, eds. Harrison's Principles of Internal Medicine. 11th ed. New York, NY: McGraw-Hill;1987:1753-1774.

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
002006 Renin Activity, Plasma 2915-7 002006 Renin Activity, Plasma ng/mL/hr 2915-7

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