Can Lisinopril Cause Hyponatremia (Low Sodium)?
Yes, lisinopril can cause hyponatremia, though this is a rare adverse effect that is far less commonly recognized than its well-known association with hyperkalemia (high potassium). 1, 2, 3, 4
Mechanism of Hyponatremia with ACE Inhibitors
The mechanism by which lisinopril causes hyponatremia differs fundamentally from its effect on potassium:
- ACE inhibitors block peripheral conversion of angiotensin I to angiotensin II, but increased circulating angiotensin I can still enter the brain where it is converted to angiotensin II. 4
- This central angiotensin II stimulates thirst and triggers inappropriate release of antidiuretic hormone (ADH) from the hypothalamus, leading to water retention and dilutional hyponatremia—essentially causing a syndrome of inappropriate antidiuretic hormone secretion (SIADH). 4
Clinical Presentation and Severity
Lisinopril-associated hyponatremia can be severe and symptomatic:
- Case reports document serum sodium levels as low as 101-109 mEq/L in patients on lisinopril, presenting with seizures, altered mental status, headaches, nausea, and neurological symptoms. 1, 2, 4
- The hyponatremia typically develops weeks to months after initiating or increasing the dose of lisinopril. 1, 4
- Laboratory findings consistent with SIADH include low serum osmolality, inappropriately concentrated urine (high urine osmolality), and elevated urine sodium. 1, 4
Contrast with Potassium Effects
It is critical to understand that lisinopril has opposite effects on sodium versus potassium:
- Lisinopril causes potassium RETENTION (hyperkalemia risk), not depletion, through inhibition of the renin-angiotensin-aldosterone system. 5
- This contrasts sharply with thiazide diuretics, which cause potassium depletion but sodium retention. 5
- The risk of hyperkalemia with lisinopril ≥10 mg daily is well-established and increases with renal dysfunction (creatinine >1.6 mg/dL), concomitant potassium supplements, or aldosterone antagonists. 6, 5
Management When Hyponatremia Occurs
When lisinopril-associated hyponatremia is suspected:
- Discontinue lisinopril immediately—case reports demonstrate rapid normalization of sodium levels after stopping the medication. 1, 2, 4
- Implement fluid restriction (typically 1000 mL/day) during the acute correction phase. 4
- Rule out other causes of SIADH including thyroid dysfunction, adrenal insufficiency, and pulmonary disease. 1, 4
- Switch to an alternative antihypertensive agent from a different class (e.g., calcium channel blockers like verapamil have been used successfully after lisinopril discontinuation). 1
- Monitor serum sodium closely during correction—in documented cases, sodium normalized within days to weeks and remained stable off lisinopril for years. 1, 4
Clinical Pitfalls and Monitoring
Key considerations to avoid missing this diagnosis:
- Hyponatremia from lisinopril is rare but serious—maintain a high index of suspicion in patients presenting with neurological symptoms or unexplained hyponatremia after starting or increasing ACE inhibitors. 3
- The FDA label for lisinopril specifically recommends starting at 2.5 mg once daily in patients with baseline hyponatremia (serum sodium <130 mEq/L) when used for heart failure, acknowledging this risk. 7
- Do not confuse the electrolyte effects: while hyperkalemia is the common and expected electrolyte disturbance with lisinopril, hyponatremia can occur through a completely different mechanism. 5, 4
- In patients with renal impairment, lisinopril accumulates and may have prolonged effects—dose adjustment is required when creatinine clearance is ≤30 mL/min. 7, 8