Do thiazide diuretics (thiazide diuretics) increase serum sodium levels?

From the Guidelines

Thiazide diuretics do not increase sodium levels in the body, but rather decrease them by promoting sodium and water excretion in the urine. These medications, such as hydrochlorothiazide and chlorthalidone, work by blocking sodium reabsorption in the distal convoluted tubule of the kidney 1. The use of thiazide diuretics is recommended for the management of hypertension, and they may be effective even in patients with advanced chronic kidney disease (CKD) 1. Some key points to consider when using thiazide diuretics include:

• They can cause electrolyte level abnormalities, including hyponatremia, particularly in the elderly 1
• They may be effective for blood pressure lowering and are associated with a lower risk of incident heart failure 1
• Electrolyte levels and eGFR should be checked within 4 weeks of initiation of treatment with a thiazide and after dose escalation 1
• Typical doses range from 12.5-50 mg daily for hydrochlorothiazide or 12.5-25 mg daily for chlorthalidone
• Patients taking thiazide diuretics should be monitored for electrolyte imbalances, particularly potassium depletion (hypokalemia), and may require potassium supplements or potassium-sparing diuretics in combination with thiazides to maintain proper electrolyte balance.

From the FDA Drug Label

Hydrochlorothiazide blocks the reabsorption of sodium and chloride ions, and it thereby increases the quantity of sodium traversing the distal tubule and the volume of water excreted.

• Thiazide diuretics, such as hydrochlorothiazide, do not increase sodium in the body, but rather increase the excretion of sodium in the urine.
• The drug blocks the reabsorption of sodium ions in the distal tubule, leading to an increase in sodium excretion. 2

From the Research

Thiazide Diuretics and Sodium Levels

• Thiazide diuretics are known to increase salt and water excretion primarily by inhibiting mechanisms for electroneutral sodium and chloride transport by distal convoluted tubule cells 3.
• The use of thiazide diuretics can lead to hyponatremia, a condition where the concentration of sodium in the blood is lower than normal 4, 5.
• Thiazides may impair diluting ability in several ways, including inhibition of sodium and chloride transport at cortical diluting sites, stimulation of vasopressin release, and reduction of glomerular filtration and enhanced proximal water reabsorption 5.
• Urinary sodium excretion did not differ significantly between patients with thiazide-induced hyponatraemia and controls 4.
• Thiazide diuretics reduce blood pressure, although the mechanisms by which they chronically lower BP remain unknown, and they present a flat dose-response curve that explains why high doses are associated with adverse effects, particularly electrolyte changes and metabolic abnormalities 6.

Mechanism of Action

• Thiazides and thiazide-like diuretics inhibit the electroneutral Na(+)-Cl(-) cotransporter located on the apical membrane of the early segment of the distal convoluted tubule 6.
• The inhibition of sodium and chloride absorption by thiazides can stimulate potassium secretion and calcium absorption 3.
• Thiazides can also inhibit carbonic anhydrase, which can contribute to the diuresis, but is largely buffered by the reserve transport capacity of the loop of Henle 3.

Clinical Implications

• Thiazide diuretics should be avoided in frail elderly patients with chronically high water intake or in others who depend on the excretion of maximally dilute urine to maintain fluid balance 5.
• The ability to dilute the urine is restored when the diuretic is discontinued and volume deficits are repaired, which can lead to inadvertent rapid correction of hyponatremia 5.
• Thiazide diuretics remain an effective and safe therapeutic alternative in the treatment of hypertension, particularly at low doses, and their ability to increase the efficacy of nearly all other classes of antihypertensives makes them a highly versatile therapeutic intervention 6.