What is the significance of the Aldosterone (a steroid hormone) to Renin (an enzyme) ratio?

From the Guidelines

The aldosterone-renin ratio (ARR) is a crucial diagnostic tool for identifying primary aldosteronism, and its significance lies in its ability to detect autonomous aldosterone production, which is a common cause of secondary hypertension, as stated in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. The ARR compares the level of aldosterone, a hormone that increases blood pressure by promoting sodium retention and potassium excretion, to renin, an enzyme that normally regulates aldosterone production. An elevated ARR, typically above 20-40 ng/dL per ng/mL/hr depending on the laboratory, suggests autonomous aldosterone production independent of renin control, which is the hallmark of primary aldosteronism. When evaluating patients with resistant hypertension, hypertension with hypokalemia, or hypertension at a young age, the ARR serves as an initial screening test. Some key points to consider when interpreting the ARR include:

• The test should be performed in the morning with the patient seated, and potassium levels should be normalized before testing.
• Certain medications, such as spironolactone, eplerenone, and other potassium-sparing diuretics, should be discontinued for at least 4-6 weeks before testing, while ACE inhibitors, ARBs, and diuretics should be stopped for 2 weeks if possible.
• A positive ARR requires confirmation with additional tests, such as salt loading or captopril suppression tests, before proceeding to adrenal imaging to determine if the condition is caused by an adrenal adenoma or bilateral adrenal hyperplasia, which guides treatment decisions between surgery or medical management, as recommended by 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. It is essential to note that the ARR can be influenced by the presence of very low renin levels, and the plasma aldosterone concentration should be at least 10 ng/dL to interpret the test as positive, as stated in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1. Overall, the ARR is a valuable tool in the diagnosis of primary aldosteronism, and its proper interpretation and application can lead to improved patient outcomes, including reduced morbidity, mortality, and enhanced quality of life, as highlighted in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.

From the Research

Significance of Aldosterone Renin Ratio

The aldosterone renin ratio (ARR) is a significant tool in the evaluation of primary aldosteronism, a common cause of secondary hypertension associated with excess cardiovascular morbidities 2. The ratio reflects aldosterone hypersecretion in regard to its principal trophin renin and is currently considered the most reliable tool for primary aldosteronism screening 3.

Diagnostic Criteria

• An aldosterone to renin ratio of 50 has a 100% specificity and 92% sensitivity for detecting primary aldosteronism 4.
• An aldosterone to renin ratio of > 2000 is suggestive of an aldosterone producing adenoma 4.
• An elevated aldosterone-renin ratio (greater than 30) indicates independent aldosterone secretion (i.e., aldosteronism) 5.
• A plasma aldosterone >400 pmol/l together with renin activity < or = 0.5 pmol/ml/h should trigger further investigations for an adrenal adenoma 6.

Clinical Applications

• The ARR is used as a screening tool for primary aldosteronism in patients with resistant hypertension, as well as those with well-controlled hypertension and a first-degree relative with primary aldosteronism, hypokalemia, an adrenal nodule, atrial fibrillation, obstructive sleep apnea, or a family history of an early stroke 5.
• A low plasma renin is a sufficient and simple way of detecting spironolactone-responders among patients with resistant hypertension 6.
• The ARR can help differentiate between unilateral and bilateral adrenal production of aldosterone, guiding treatment decisions 5.

Limitations and Considerations

• The ARR can be affected by various factors, including laboratory methods, posture, antihypertensive medication, and dietary salt intake 3.
• Differentiation between low-renin essential hypertension and primary aldosteronism can be difficult and probably arbitrary 3.
• The ARR should be interpreted in the context of clinical presentation and other diagnostic tests to confirm primary aldosteronism 5.