Do I need to check electrolytes when titrating up Angiotensin-Converting Enzyme (ACE) inhibitor or Angiotensin Receptor Blocker (ARB) medication for hypertension?

From the Guidelines

Yes, you should check electrolytes when titrating ACE inhibitors or ARBs for hypertension, specifically monitoring serum potassium and creatinine levels after initiation of treatment and during uptitration, particularly among individuals with reduced glomerular filtration who are at increased risk of hyperkalemia and AKI. This is based on the most recent evidence from the 2025 standards of care in diabetes, which emphasizes the importance of detecting and managing hyperkalemia and acute kidney injury (AKI) in patients treated with ACE inhibitors and ARBs 1.

Key Considerations

• The risk of hyperkalemia and AKI is higher in patients with pre-existing renal impairment, diabetes, or those taking potassium supplements or potassium-sparing diuretics.
• ACE inhibitors and ARBs work by blocking the renin-angiotensin-aldosterone system, which normally promotes potassium excretion, so inhibiting this pathway can lead to potassium retention.
• Additionally, these medications can reduce glomerular filtration pressure in the kidneys, potentially causing a temporary increase in creatinine levels.
• If potassium exceeds 5.5 mEq/L or creatinine increases by more than 30% from baseline, consider reducing the dose or consulting with a specialist.

Monitoring Recommendations

• Monitor serum creatinine and potassium levels after initiation of treatment with an ACE inhibitor or ARB, and during uptitration of these medications.
• Monitor serum potassium and creatinine levels at least annually in patients treated with an ACE inhibitor, angiotensin receptor blocker, or diuretic, as recommended by the 2021 standards of medical care in diabetes 1.
• More frequent monitoring may be necessary in patients with reduced glomerular filtration or those at higher risk of hyperkalemia and AKI.

Clinical Implications

• The importance of monitoring electrolytes and renal function in patients treated with ACE inhibitors and ARBs is also highlighted in earlier guidelines, such as the 2018 standards of medical care in diabetes 1 and the 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults 1.
• However, the most recent evidence from the 2025 standards of care in diabetes should be prioritized in clinical decision-making 1.

From the FDA Drug Label

1. 4 Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Closely monitor blood pressure, renal function and electrolytes in patients on lisinopril and other agents that affect the RAS.

Yes, when titrating up ACE inhibitor or ARB medication for hypertension, it is necessary to check electrolytes, as there is an increased risk of hyperkalemia and changes in renal function.

• Monitor electrolytes
• Monitor renal function
• Monitor blood pressure 2

From the Research

Titrating ACE Inhibitors or ARBs for Hypertension

When titrating up ACE inhibitor or ARB medication for hypertension, it is essential to consider the potential effects on electrolytes.

• The study 3 found that uptitrating the dose of losartan or ramipril led to a slight increase in plasma potassium, but no significant changes in plasma sodium, urea, or creatinine.
• Another study 4 found that the risk of hyperkalemia was higher in ACEi/ARB users than in nonusers, highlighting the need for close clinical monitoring.
• However, the study 3 also found that the rate of adverse events did not significantly increase, and no changes in plasma electrolytes were observed in most patients.

Monitoring Electrolytes

Given the potential risks of hyperkalemia associated with ACEi/ARB use, it is crucial to monitor electrolytes, particularly potassium levels, when titrating up these medications.

• The study 4 suggests that patients with AKI may have a survival benefit by continued use of ACEi/ARB, but close monitoring of electrolytes is necessary to mitigate the risk of hyperkalemia.
• The study 5 found that ACE inhibitors remain associated with a low risk of angioedema and fatalities, but overall withdrawal rates due to adverse events are lower with ARBs than with ACE inhibitors.

Clinical Implications

In clinical practice, healthcare providers should carefully weigh the benefits and risks of titrating up ACE inhibitors or ARBs for hypertension, taking into account the potential effects on electrolytes and the individual patient's risk profile.

• The study 6 highlights the importance of controlling blood pressure and proteinuria in patients with renal disease, and the use of ACE inhibitors or ARBs can be beneficial in achieving these goals.
• The study 7 suggests that ACEIs, angiotensin II receptor antagonists, and calcium antagonists are effective and well-tolerated antihypertensive agents, but should be considered alternative drugs for first-line therapy until randomized trials show that they are at least as effective as diuretics and beta-blockers in preventing cardiovascular morbidity and mortality.