Does Lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor) cause hyperkalemia (elevated potassium levels) or hypokalemia (decreased potassium levels)?

From the Guidelines

Lisinopril, an ACE inhibitor, can cause hyperkalemia (elevated potassium levels) rather than hypokalemia. This occurs because ACE inhibitors block the formation of angiotensin II, which normally stimulates the release of aldosterone. With reduced aldosterone, the kidneys retain more potassium instead of excreting it, leading to increased potassium levels in the blood. According to the most recent study 1, treatment with ACE inhibitors can cause hyperkalemia, and serum creatinine and potassium should be monitored after initiation of treatment.

Key Points to Consider

• Patients taking lisinopril should monitor their potassium levels regularly, especially those with kidney disease, diabetes, or those taking potassium supplements or potassium-sparing diuretics.
• Normal potassium levels range from 3.5-5.0 mEq/L, and levels above 5.0 mEq/L indicate hyperkalemia.
• Symptoms of hyperkalemia include muscle weakness, fatigue, numbness, and in severe cases, cardiac arrhythmias.
• Patients should avoid high-potassium foods and supplements while taking lisinopril, and healthcare providers may need to adjust the medication dosage if significant hyperkalemia develops.
• The risk of hyperkalemia is higher in patients with reduced glomerular filtration, and serum creatinine and potassium should be monitored during treatment and following uptitration of these medications 1.

Recommendations for Clinical Practice

• Regularly monitor serum creatinine and potassium levels in patients taking lisinopril, especially those with kidney disease or diabetes.
• Adjust medication dosage if significant hyperkalemia develops.
• Educate patients on the risks of hyperkalemia and the importance of monitoring potassium levels.
• Consider alternative treatments or adjust medication regimens to minimize the risk of hyperkalemia in high-risk patients.

From the FDA Drug Label

Serum potassium should be monitored periodically in patients receiving lisinopril. Drugs that inhibit the renin angiotensin system can cause hyperkalemia Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes Lisinopril attenuates potassium loss caused by thiazide-type diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) can increase the risk of hyperkalemia. Clinical Laboratory Test Findings Serum Potassium: In clinical trials hyperkalemia (serum potassium greater than 5.7 mEq/L) occurred in 2.2% and 4.8% of lisinopril-treated patients with hypertension and heart failure, respectively

Lisinopril increases the risk of hyperkalemia (elevated potassium levels) in patients, especially those with renal insufficiency, diabetes mellitus, or those taking potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes 2, 2, 2.

• Key factors that contribute to the development of hyperkalemia include:
  • Renal insufficiency
  • Diabetes mellitus
  • Concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes
• Clinical trial findings indicate that hyperkalemia occurred in 2.2% and 4.8% of lisinopril-treated patients with hypertension and heart failure, respectively 2.

From the Research

Effect of Lisinopril on Potassium Levels

• Lisinopril, an Angiotensin-Converting Enzyme (ACE) inhibitor, can cause an increase in potassium levels, leading to hyperkalemia 3, 4.
• The risk of hyperkalemia is higher in patients with chronic kidney disease (CKD) or renal insufficiency, as they have impaired potassium excretion 3, 5.
• Studies have shown that ACE inhibitors, including lisinopril, can increase serum potassium levels by reducing aldosterone levels, which leads to decreased potassium excretion in the urine 6, 4.

Factors Influencing the Risk of Hyperkalemia

• Patients with diabetes, heart failure, or those taking potassium-sparing diuretics or potassium supplements are at higher risk of developing hyperkalemia when taking lisinopril 3, 5.
• The risk of hyperkalemia also increases with declining renal function, as measured by estimated glomerular filtration rate (eGFR) 3, 5.
• Concomitant use of diuretics can reduce the risk of hyperkalemia by increasing potassium excretion in the urine 5.

Clinical Implications

• Monitoring of serum potassium levels is recommended when initiating lisinopril therapy, especially in patients with CKD or renal insufficiency 3, 4.
• Patients should be educated on the signs and symptoms of hyperkalemia, such as muscle weakness, palpitations, and arrhythmias, and seek medical attention if they occur 4.
• Healthcare providers should be aware of the potential risk of hyperkalemia when prescribing lisinopril and take steps to minimize this risk, such as monitoring serum potassium levels and adjusting the dose or discontinuing the medication if necessary 3, 5.