Renin Activity, Plasma

Plasma, frozen

1 mL

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

Lavender-top (EDTA) tube

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.

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.

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

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).

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