Is sodium reabsorbed with thiazide (diuretic) therapy?

From the Guidelines

Thiazide diuretics inhibit sodium reabsorption in the distal convoluted tubule of the kidney, rather than promoting it. According to the 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults 1, thiazide diuretics act in the distal portion of the tubule to increase the fractional excretion of sodium to only 5% to 10% of the filtered load. This mechanism of action is distinct from loop diuretics, which act at the loop of Henle to increase sodium excretion up to 20% to 25% of the filtered load. The key points to consider when using thiazide diuretics include:

• Inhibition of sodium reabsorption in the distal convoluted tubule
• Increase in sodium and water excretion in the urine
• Reduction in blood volume and subsequent lowering of blood pressure
• Potential for electrolyte imbalances, particularly hypokalemia, due to potassium and magnesium loss
• Decreased calcium excretion, which can be beneficial in certain patients

As noted in the guidelines 1, thiazide diuretics may be preferred in hypertensive HF patients with mild fluid retention because they confer more persistent antihypertensive effects. However, their effectiveness is reduced in patients with impaired renal function, making loop diuretics a better option for most patients with heart failure.

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.

• Sodium reabsorption is blocked by thiazide diuretics, such as hydrochlorothiazide.
• The use of thiazide diuretics increases the quantity of sodium traversing the distal tubule.
• This results in an increase in the volume of water excreted. 2

From the Research

Mechanism of Thiazide Diuretics

• Thiazide diuretics increase salt and water excretion primarily by inhibiting mechanisms for electroneutral sodium and chloride transport by distal convoluted tubule cells 3.
• They inhibit the electroneutral Na(+)-Cl(-) cotransporter located on the apical membrane of the early segment of the distal convoluted tubule 4.
• This inhibition of sodium and chloride absorption leads to increased distal tubule fluid flow rate, which in turn stimulates potassium secretion and calcium absorption 3.

Effect on Sodium Reabsorption

• Thiazide diuretics do not promote sodium reabsorption; instead, they inhibit sodium reabsorption in the distal convoluted tubule 3, 4.
• The inhibition of sodium reabsorption leads to increased sodium excretion in the urine, which is the primary mechanism by which thiazide diuretics lower blood pressure 4, 5.

Clinical Implications

• Thiazide diuretics are effective in treating hypertension and edematous states, and are often used in combination with other antihypertensive agents 4, 5, 6.
• They can cause electrolyte changes and metabolic abnormalities, particularly at high doses, but these effects can be minimized at low doses 4, 7.
• Thiazide diuretics can also cause hyponatremia, particularly in frail elderly patients or those with high water intake, due to impaired water excretion and cation depletion 7.