Can Angiotensin-Converting Enzyme (ACE) inhibitors cause hyponatremia?

ACE Inhibitors and Hyponatremia

ACE inhibitors can cause hyponatremia, particularly in patients with heart failure, though this is not among their most common adverse effects. The risk is highest in specific patient populations and clinical scenarios.

Mechanism and Risk Factors

ACE inhibitors may contribute to hyponatremia through several mechanisms:

1. Syndrome of Inappropriate Antidiuretic Hormone (SIADH):

   • Rare but documented cases show ACE inhibitors can induce SIADH 1, 2, 3
   • This can occur regardless of how long the patient has been taking the medication

2. Heart Failure Context:

   • In heart failure patients, severe hyponatremia (serum sodium <130 mmol/L) increases the risk of symptomatic hypotension when starting ACE inhibitors 4
   • Paradoxically, ACE inhibitors can also improve hyponatremia in some heart failure patients by increasing the kidney's diluting ability 5

High-Risk Patient Populations

The American College of Cardiology/American Heart Association guidelines identify patients at highest risk for ACE inhibitor-related complications including hyponatremia 4:

• Patients with severe heart failure (Class IV)
• Patients with pre-existing hyponatremia
• Patients after recent marked diuresis
• Patients with hypovolemia
• Patients with renal insufficiency

Monitoring and Management

When using ACE inhibitors:

• Monitor serum sodium levels:

  • At baseline before starting therapy
  • Within 1-2 weeks of initiation
  • After dose increases
  • When additional factors affecting water/salt homeostasis arise 1

• If hyponatremia develops:

  • Consider discontinuing the ACE inhibitor if severe or symptomatic
  • Evaluate for other contributing factors (diuretics, fluid intake)
  • Reduce diuretic doses if possible 4
  • Liberalize salt intake if no significant fluid retention 4

Clinical Implications

While hyponatremia is not among the most commonly reported adverse effects of ACE inhibitors (compared to cough, hypotension, or hyperkalemia), clinicians should remain vigilant, especially in high-risk populations 6.

The risk of hyponatremia should not necessarily preclude the use of ACE inhibitors in appropriate patients, as these medications provide significant mortality benefits in heart failure and other conditions. However, appropriate monitoring and awareness of this potential adverse effect are essential for safe prescribing.