Does renin increase with Angiotensin-Converting Enzyme Inhibitor (ACEI) medication?

From the Guidelines

Yes, renin levels typically increase with ACE inhibitor (ACEI) medication use. When you take medications like lisinopril, enalapril, or ramipril, they block the conversion of angiotensin I to angiotensin II, which normally provides negative feedback to renin production. Without this feedback inhibition, the kidneys respond by increasing renin release. This is a normal compensatory response to ACEI therapy and doesn't indicate treatment failure. In fact, this increase in renin is often used as a marker of effective ACEI activity in the body, as noted in the 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure 1. The elevated renin levels don't typically cause problems because the downstream effects of the renin-angiotensin-aldosterone system remain blocked by the medication.

Key Points to Consider

• ACE inhibitors reduce morbidity and mortality in heart failure with reduced ejection fraction (HFrEF) by blocking the conversion of angiotensin I to angiotensin II, which leads to increased renin release as a compensatory response.
• This increase in renin is a marker of effective ACEI activity and does not typically require a change in therapy.
• The use of ACE inhibitors is beneficial for patients with prior or current symptoms of chronic HFrEF to reduce morbidity and mortality, as established by randomized controlled trials (RCTs) 1.
• ACE inhibitors should be started at low doses and titrated upward to doses shown to reduce the risk of cardiovascular events in clinical trials, with caution given to patients with low systemic blood pressures, renal insufficiency, or elevated serum potassium.

Clinical Implications

• Doctors sometimes monitor renin levels along with other parameters to assess treatment effectiveness, but isolated increases in renin while on ACEIs are expected and don't usually require any change in therapy.
• The clinical strategy of inhibition of the renin-angiotensin system with ACE inhibitors, ARBs, or ARNI in conjunction with evidence-based beta blockers and aldosterone antagonists is recommended for patients with chronic HFrEF to reduce morbidity and mortality, as stated in the 2017 ACC/AHA/HFSA focused update 1.

From the FDA Drug Label

Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity.

The use of ACE inhibitors, such as lisinopril, increases plasma renin activity due to the removal of angiotensin II negative feedback on renin secretion 2.

From the Research

Effect of ACEI Medication on Renin Levels

• The effect of ACE inhibitors on renin levels has been studied in several research papers 3, 4, 5, 6, 7.
• According to a study published in the Journal of cardiovascular pharmacology, treatment with an ACE inhibitor, such as ramipril, increases vascular renin levels in hypertensive patients 5.
• Another study published in Hypertension found that ACE inhibitors raise renin levels, which can cause false-negative results in the aldosterone/renin ratio (ARR) test used to detect primary aldosteronism 6.
• The increase in renin levels is a result of the feedback mechanism that occurs when ACE inhibitors block the conversion of angiotensin I to angiotensin II, leading to an increase in renin release 5, 6.
• The studies suggest that ACE inhibitors can increase renin levels, which can have implications for the diagnosis and treatment of certain conditions, such as primary aldosteronism 6.

Mechanism of Action

• The mechanism of action of ACE inhibitors involves blocking the conversion of angiotensin I to angiotensin II, which leads to a decrease in blood pressure and an increase in renin release 5, 7.
• The increase in renin release is a result of the feedback mechanism that occurs when the levels of angiotensin II decrease, leading to an increase in renin release 5, 6.
• The studies suggest that the mechanism of action of ACE inhibitors is complex and involves multiple pathways, including the renin-angiotensin-aldosterone system 3, 4, 5, 6, 7.

Clinical Implications

• The increase in renin levels caused by ACE inhibitors can have clinical implications, such as false-negative results in the ARR test used to detect primary aldosteronism 6.
• The studies suggest that clinicians should be aware of the potential effects of ACE inhibitors on renin levels and take this into account when interpreting test results or making treatment decisions 5, 6.