Is thiazide diuretic (Thiazide Diuretic) therapy safe in patients with Chronic Kidney Disease (CKD)?

From the Guidelines

Thiazide diuretics can be used safely in patients with chronic kidney disease (CKD), but their effectiveness and safety depend on the stage of CKD and require close monitoring. For patients with mild to moderate CKD (stages 1-3, GFR >30 mL/min), thiazides like hydrochlorothiazide (12.5-25 mg daily) or chlorthalidone (12.5-25 mg daily) can still be effective for blood pressure control and volume management, as shown in a study published in the American Journal of Kidney Diseases 1. However, in advanced CKD (stages 4-5, GFR <30 mL/min), thiazides generally lose their effectiveness because they work by inhibiting sodium reabsorption in the distal tubule, which requires adequate kidney function. Some guidelines, such as the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APHA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults, suggest that loop diuretics like furosemide (20-80 mg once or twice daily) or torsemide (10-100 mg daily) are typically more appropriate for these patients 1. When using thiazides in CKD patients, close monitoring is essential for electrolyte imbalances (particularly hyponatremia, hypokalemia), worsening kidney function, and metabolic abnormalities like hyperuricemia and glucose intolerance. The decision to use thiazides should be individualized based on the patient's specific GFR, blood pressure goals, volume status, and tolerance to medication side effects. Key considerations include:

• Monitoring potassium levels closely when combining thiazide diuretics with loop diuretics or potassium-sparing diuretics
• Avoiding the use of thiazides in patients with significant CKD (e.g., GFR <45 mL/min) or those with a history of acute gout unless the patient is on uric acid–lowering therapy
• Being aware of the potential for hyperkalemia, especially in patients with CKD or those on K+ supplements or K-sparing drugs.

From the FDA Drug Label

Renal Disease: Cumulative effects of the thiazides may develop in patients with impaired renal function. In such patients, thiazides may precipitate azotemia. The use of thiazide diuretics, such as hydrochlorothiazide, may not be safe in patients with Chronic Kidney Disease (CKD) as they can precipitate azotemia in patients with impaired renal function 2.

• Key considerations:
  • Cumulative effects of thiazides may develop in patients with impaired renal function
  • Thiazides may precipitate azotemia in such patients It is recommended to exercise caution when using thiazide diuretics in patients with CKD.

From the Research

Safety of Thiazide Diuretic Therapy in Patients with CKD

• The safety and efficacy of thiazide diuretic therapy in patients with Chronic Kidney Disease (CKD) have been debated, with some studies suggesting that thiazides may not be effective in patients with advanced CKD 3.
• However, recent studies have shown that thiazide diuretics can be effective in lowering blood pressure and reducing cardiovascular risk in patients with CKD, even in those with advanced disease 4, 5, 6.
• The combination of thiazide diuretics with loop diuretics has been shown to be effective in controlling volume overload and lowering blood pressure in patients with CKD, particularly in those with severely impaired kidney function 4, 7.
• While thiazide diuretics may be associated with side effects such as electrolyte abnormalities, hypokalemia, and volume depletion, these can be managed with close monitoring and careful dosing 5, 6.

Efficacy of Thiazide Diuretics in CKD

• Studies have shown that thiazide diuretics can improve blood pressure control and reduce proteinuria in patients with CKD, including those with type 2 diabetic kidney disease 5, 7.
• The antihypertensive efficacy of chlorthalidone, a long-acting thiazide-like diuretic, has been documented in stage 4 CKD patients with poorly controlled hypertension 6.
• Thiazide diuretics have been shown to cause a negative sodium balance and reduce body fluids, which can lead to improvements in hypertension control 6.

Considerations for Thiazide Diuretic Use in CKD

• While thiazide diuretics may be effective in patients with CKD, their use should be carefully considered and monitored, particularly in those with advanced disease or significant electrolyte abnormalities 3, 5, 6.
• The combination of thiazide diuretics with loop diuretics may be effective in controlling volume overload and lowering blood pressure in patients with CKD, but requires careful dosing and monitoring 4, 7.