Which type of diuretic, thiazide (e.g. hydrochlorothiazide) or loop (e.g. furosemide), is more likely to cause hyponatremia?

From the Guidelines

Thiazide diuretics are more likely to cause hyponatremia than loop diuretics. This is because thiazide diuretics, such as hydrochlorothiazide, impair the kidney's ability to dilute urine by blocking sodium chloride reabsorption in the distal convoluted tubule, while simultaneously allowing continued water reabsorption, leading to relatively more water retention compared to sodium and resulting in dilutional hyponatremia 1. In contrast, loop diuretics, such as furosemide, block sodium reabsorption in the thick ascending limb of the loop of Henle, interfering with the kidney's concentrating mechanism and causing more balanced losses of both water and sodium.

The mechanism of action of these diuretics is crucial in understanding their effects on sodium and water balance in the body. Thiazide diuretics increase the fractional excretion of sodium to only 5% to 10% of the filtered load and tend to decrease free water clearance, which can lead to hyponatremia, especially in vulnerable patients such as the elderly, females, and those with low body weight 1. Loop diuretics, on the other hand, increase sodium excretion up to 20% to 25% of the filtered load and enhance free water clearance, making them less likely to cause hyponatremia.

Key points to consider in clinical practice include:

• Monitoring sodium levels closely in patients taking thiazide diuretics, especially during the first few weeks of therapy when the risk of hyponatremia is highest.
• Ensuring adequate sodium intake in vulnerable patients.
• Being aware of the potential for hyponatremia in patients with heart failure who are treated with thiazide diuretics, as hyponatremia can complicate heart failure management 1.
• Considering the use of loop diuretics instead of thiazide diuretics in patients at high risk of hyponatremia, or using them in combination with other diuretics in patients with refractory edema.

From the FDA Drug Label

WARNING Furosemide is a potent diuretic which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion. OVERDOSAGE The principal signs and symptoms of overdose with furosemide are dehydration, blood volume reduction, hypotension, electrolyte imbalance, hypokalemia and hypochloremic alkalosis, and are extensions of its diuretic action.

The FDA drug label does not answer the question.

From the Research

Comparison of Thiazide and Loop Diuretics

• Thiazide diuretics, such as hydrochlorothiazide, are more likely to cause hyponatremia compared to loop diuretics, such as furosemide 2, 3, 4.
• The mechanism of thiazide-induced hyponatremia involves impaired water excretion, cation depletion, and reduced ability to dilute urine 3, 5.
• Loop diuretics are less commonly associated with hyponatremia, as they primarily act on the loop of Henle and do not significantly impair water excretion 4.

Risk Factors for Thiazide-Induced Hyponatremia

• Elderly women are at higher risk of developing severe hyponatremia due to thiazide diuretics 2.
• Patients with high water intake, such as those with psychogenic polydipsia or heavy beer drinking, are also at increased risk 3.
• The use of non-steroidal anti-inflammatory drugs (NSAIDs) concurrently with thiazide diuretics can increase the risk of hyponatremia 2.

Clinical Manifestations and Treatment

• Thiazide-induced hyponatremia can present with a range of symptoms, from mild dizziness and headache to severe neurological symptoms, including lethargy and confusion 2, 5.
• Treatment involves cessation of thiazide use, cation repletion, and oral fluid restriction, with 3% saline solution indicated in severely symptomatic cases 5.
• Overly rapid correction of chronic hyponatremia should be avoided to prevent osmotic demyelination syndrome 2, 3, 5.