Can triamterene (HCTZ) [hydrochlorothiazide] cause hyponatremia, especially in patients with a history of kidney disease or impaired renal function?

Triamterene-HCTZ and Hyponatremia Risk

Yes, triamterene-HCTZ can cause hyponatremia, though the primary culprit is the hydrochlorothiazide component rather than triamterene itself. Thiazide diuretics are well-established causes of hyponatremia, particularly in elderly patients, and this risk persists even when combined with potassium-sparing agents like triamterene.

Mechanism and Risk Profile

The hydrochlorothiazide component causes hyponatremia through impaired free water excretion at low antidiuretic hormone levels, combined with increased water intake and reduced urea-mediated water excretion 1. This mechanism is distinct from the potassium-sparing effects of triamterene, which primarily blocks epithelial sodium channels in the collecting duct 2.

Thiazide-induced hyponatremia is associated with markedly impaired free water excretion even when ADH and aquaporin-2 levels are suppressed 1. Patients who develop this complication demonstrate higher ad libitum water intake (2543 ± 925 ml vs 1828 ± 624 ml in controls) and lower urea excretion, which predicts the severity of sodium decline 1.

High-Risk Patient Populations

Elderly patients, particularly women, face substantially elevated risk for thiazide-induced hyponatremia 3, 4. Additional risk factors include:

• Patients with chronic kidney disease: Those with severe CKD show hyponatremia rates of 47.1% compared to 34.4% in those with normal renal function 4
• Heart failure patients: Hydrochlorothiazide use independently predicts hyponatremia across all stages of renal function 4
• Concurrent use of mineralocorticoid receptor antagonists: This combination increases hyponatremia risk in patients with normal renal function and mild-to-moderate CKD 4
• Female sex and alcohol consumption: These are independent predictors in patients with normal renal function 4

Clinical Presentation and Severity

Hyponatremia from thiazide diuretics typically presents with nonspecific symptoms including generalized weakness, which can begin within 2 weeks of initiating therapy 3. Severe cases can present with sodium levels as low as 120 mmol/L, requiring hospitalization 3. The condition is potentially life-threatening if not promptly recognized and treated 3.

Critical Monitoring Requirements

Check serum sodium within 5-7 days after initiating triamterene-HCTZ therapy, then continue monitoring every 5-7 days until values stabilize 5. This is particularly crucial in:

• Elderly patients (especially women)
• Those with any degree of renal impairment
• Patients on concurrent loop diuretics or mineralocorticoid receptor antagonists
• Those with heart failure

Management Algorithm

If hyponatremia develops (sodium <135 mEq/L):

1. Immediately discontinue the hydrochlorothiazide component 3
2. Implement free water restriction 3
3. Check concurrent medications: Avoid combining with other drugs that impair sodium balance, including mineralocorticoid receptor antagonists in patients with normal renal function 4
4. Monitor sodium levels closely until normalization occurs

For patients requiring continued diuretic therapy after hyponatremia resolution:

• Consider switching to loop diuretics (furosemide, bumetanide, torsemide), which have lower hyponatremia risk 6
• If blood pressure control is the primary indication, consider dihydropyridine calcium channel blockers, which show protective effects against hyponatremia across all CKD stages 4
• Avoid re-challenging with thiazide diuretics, as patients with prior thiazide-induced hyponatremia remain at high risk for recurrence 1

Important Caveats

The triamterene component itself can cause different electrolyte disturbances, most notably hyperkalemia rather than hyponatremia 6, 5. In rare cases, triamterene has been associated with irreversible renal failure due to intratubular crystal deposition 7. Monitor both sodium and potassium levels, as well as renal function, when using this combination 5.

Do not assume the potassium-sparing properties of triamterene protect against thiazide-induced hyponatremia—the mechanisms are independent, and both electrolyte disturbances can occur simultaneously or separately 2, 1.