What are the causes of elevated renin (Renin) levels?

From the Guidelines

Elevated renin levels are primarily caused by decreased renal perfusion, which can occur in conditions like renal artery stenosis, as noted in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. The causes of elevated renin levels can be multifactorial, including physiological and pathological conditions.

• Renal artery stenosis, which can lead to renovascular hypertension (RVH), is a major cause of elevated renin levels, as it decreases renal perfusion pressure and activates the renin–angiotensin–aldosterone system (RAAS) 1.
• Other causes of elevated renin levels include volume depletion, heart failure, and certain medications such as diuretics, ACE inhibitors, and angiotensin receptor blockers.
• Endocrine disorders like Addison's disease, Bartter syndrome, and Gitelman syndrome can also contribute to elevated renin levels.
• Malignant hypertension and renovascular hypertension are important causes to consider, as they can lead to significant elevations in renin levels.
• Pregnancy can normally increase renin levels due to estrogen effects, and renin-secreting tumors, although rare, can cause significant elevations. The physiological basis for these elevations involves the body's attempt to maintain blood pressure and fluid balance when it senses decreased renal perfusion or sodium depletion, triggering the juxtaglomerular cells in the kidneys to release more renin, which then initiates the cascade to produce angiotensin II and ultimately aldosterone to increase blood pressure and sodium retention 1. Key diagnostic tests for RVH include imaging tests such as renal artery Doppler ultrasound, abdominal CT angiography, or magnetic resonance imaging (MRI), as recommended in the 2024 ESC guidelines 1.

From the FDA Drug Label

Renin is secreted by the kidney in response to decreases in blood volume and renal perfusion. The causes of elevated renin (Renin) levels are:

• Decreases in blood volume
• Decreases in renal perfusion 2 Note: The provided text does not give a comprehensive list of all possible causes of elevated renin levels, only the ones mentioned in relation to the mechanism of action of aliskiren.

From the Research

Causes of Elevated Renin Levels

Elevated renin levels can be caused by various factors, including:

• Renal artery stenosis, which can lead to renal hypoperfusion and activation of the renin-angiotensin system 3
• Use of certain medications, such as diuretics, ACE inhibitors, and ARBs, which can interrupt physiological feedback for renal renin release and lead to reactive elevation of circulating active renin 4
• Low renin essential hypertension, which may have an enhanced adrenal response to angiotensin II as the underlying mechanism 5
• High renin essential hypertension, which may have a decreased adrenal response to angiotensin II as the primary mechanism for their high renin levels and potentially for their elevated blood pressure 5
• Renovascular disease, which includes renal artery stenosis, renovascular hypertension, and azotemic renovascular disease (ischemic nephropathy) 3

Relationship Between Renin Levels and Other Factors

There is a significant relationship between renin levels and other factors, such as:

• Blood pressure, which can be decreased by converting enzyme inhibitors like enalapril, and is related to pretreatment plasma concentrations of active renin and angiotensin II 6
• Angiotensin II, which can be decreased by enalapril treatment, and is related to the decrease in blood pressure 6
• Renal function, which can be affected by enalapril treatment, and may lead to a reduction in effective renal plasma flow via the affected kidney 6

Clinical Implications

Elevated renin levels can have significant clinical implications, including:

• Increased risk of cardiovascular and kidney diseases 7
• Need for individualized management decisions for patients with renovascular disease 3
• Importance of considering renal arterial disease as one aspect of atherosclerotic disease 3
• Potential benefits of using direct renin inhibitors like aliskiren in patients with hypertension and concomitant diabetes, nephropathy, and proteinuria 4