What does low plasma renin (Renin) activity indicate?

From the Guidelines

Low plasma renin levels are highly suggestive of primary aldosteronism, a condition characterized by autonomous aldosterone production, which can lead to hypertension and hypokalemia. This condition is often associated with an aldosterone-to-renin ratio greater than 30, as stated in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1. The diagnosis of primary aldosteronism requires a confirmatory test, such as an intravenous saline suppression test or oral salt-loading test, and treatment may involve mineralocorticoid receptor antagonists like spironolactone or eplerenone, or surgical removal of adrenal adenomas.

Some key points to consider when evaluating low plasma renin levels include:

• The aldosterone-to-renin ratio is a useful screening test for primary aldosteronism, but its interpretation can be influenced by certain medications, such as mineralocorticoid receptor antagonists and direct renin inhibitors 2
• A high aldosterone-to-renin ratio (> 20) with a serum aldosterone level > 16 ng/dL and a plasma renin activity < 0.6 ng/mL per hour is suggestive of primary aldosteronism, particularly in patients taking ACE inhibitors or ARBs 2
• Treatment of primary aldosteronism depends on the underlying cause, but may include mineralocorticoid receptor antagonists, surgical removal of adrenal adenomas, or adjustment of medications that may be contributing to the low renin state

It is essential to note that low plasma renin levels can also be seen in other medical conditions, such as Cushing's syndrome, congenital adrenal hyperplasia, Liddle syndrome, and chronic kidney disease, as well as in patients taking certain medications like beta-blockers, NSAIDs, and mineralocorticoids. Therefore, a thorough evaluation and diagnosis are necessary to determine the underlying cause of low plasma renin levels and to guide appropriate treatment.

From the Research

Low Plasma Renin

• Low plasma renin is often associated with primary aldosteronism (PA), a condition characterized by excessive production of aldosterone 3.
• The aldosterone-to-renin ratio (ARR) is used as a screening test for PA, and a low plasma renin level can result in a high ARR, indicating potential PA 4.
• A study found that an ARR threshold based on plasma immunoreactive renin concentration (irR) of > 150 pmol/ng may indicate primary aldosteronism 4.
• Low plasma renin levels can also be seen in patients with bilateral hyperaldosteronism, who are often treated with low-dose mineralocorticoid receptor antagonists (MRAs) 3.
• Mineralocorticoid receptor antagonists can increase renin levels and decrease the aldosterone-to-renin ratio, which can affect the diagnostic accuracy of screening tests for primary aldosteronism 5.

Diagnostic Implications

• Low plasma renin levels can be a diagnostic challenge, as they can be seen in various conditions, including primary aldosteronism and bilateral hyperaldosteronism [(3, 4)].
• The use of ARR as a screening test for PA requires careful interpretation, as low plasma renin levels can result in a high ARR, even in the absence of PA 4.
• Further testing, such as adrenal venous sampling (AVS) or plasma steroid assays, may be necessary to confirm the diagnosis of PA in patients with low plasma renin levels 3.

Treatment Implications

• Patients with low plasma renin levels and confirmed PA may benefit from treatment with MRAs, such as spironolactone or finerenone [(6, 7)].
• However, the use of MRAs can affect the diagnostic accuracy of screening tests for PA, and their use should be carefully considered in patients with suspected PA 5.