Is Hydrochlorothiazide (HCTZ) nephrotoxic?

From the Guidelines

Hydrochlorothiazide (HCTZ) can be hard on the kidneys, especially in individuals with pre-existing kidney disease, elderly individuals, and those taking other medications that affect kidney function, as it can cause kidney problems, electrolyte imbalances, and dehydration, which can reduce blood flow to the kidneys. HCTZ is a thiazide diuretic that works by causing the kidneys to remove more sodium and water from the body, which can help lower blood pressure. While it's generally considered safe for most people when used as prescribed, HCTZ can cause kidney problems in some situations. People with pre-existing kidney disease, elderly individuals, and those taking other medications that affect kidney function may be at higher risk for kidney issues. HCTZ can also cause electrolyte imbalances, particularly potassium depletion, which indirectly impacts kidney health. Dehydration is another concern, as excessive fluid loss can reduce blood flow to the kidneys.

Key Considerations

• The use of thiazide diuretics, such as HCTZ, should be avoided in patients with impaired renal function (creatinine clearance less than 40 mL per min) 1.
• Loop diuretics are preferred over thiazide diuretics in patients with moderate-to-severe chronic kidney disease (CKD) (eGFR <30 mL/min) 1.
• The estimated glomerular filtration rate (eGFR) should be accurately determined to adjust dose requirements of renally cleared drugs, such as HCTZ, and the CKD-EPI equation is recommended for estimating eGFR in adults of any age 1.
• Regular blood tests to monitor kidney function and electrolyte levels are essential for patients taking HCTZ, especially in those with pre-existing kidney disease or elderly individuals.
• Patients taking HCTZ should be advised to stay adequately hydrated and report any unusual symptoms like extreme thirst, severe dizziness, or changes in urination to their healthcare provider.

Dosage and Administration

• The typical dosage of HCTZ ranges from 12.5 to 50 mg daily, and the doctor will prescribe the appropriate amount based on the patient's specific condition 1.
• The dosage of HCTZ may need to be adjusted in patients with impaired renal function or elderly individuals to minimize the risk of adverse effects.
• It is essential to monitor renal function and adjust the dosage of HCTZ accordingly to prevent kidney problems and other adverse effects.

From the FDA Drug Label

Hydrochlorothiazide is eliminated primarily by renal pathways. In patients with renal disease, plasma concentrations of hydrochlorothiazide are increased and the elimination half-life is prolonged Cumulative effects of the thiazides may develop in patients with impaired renal function. In such patients, thiazides may precipitate azotemia.

Hydrochlorothiazide may be hard on kidneys, especially in patients with pre-existing renal disease, as it may precipitate azotemia and its elimination is primarily through renal pathways, leading to increased plasma concentrations and a prolonged elimination half-life in patients with impaired renal function 2 2.

• Key points:
  • Increased plasma concentrations in renal disease
  • Prolonged elimination half-life in renal disease
  • May precipitate azotemia in patients with impaired renal function

From the Research

Effects of HCTZ on Kidneys

• The use of thiazide diuretics, such as HCTZ, in patients with chronic kidney disease (CKD) has been a topic of debate 3, 4, 5, 6.
• Some studies suggest that HCTZ can be effective in lowering blood pressure and reducing proteinuria in patients with CKD, even in advanced stages 4, 6.
• However, other studies have raised concerns about the potential negative effects of HCTZ on kidney function, particularly in patients with advanced CKD 3, 7.
• A study published in 2015 found that the combination of HCTZ and loop diuretics improved blood pressure levels and decreased proteinuria in patients with type 2 diabetic kidney disease, without negatively affecting kidney function 4.
• Another study published in 2014 suggested that thiazide diuretics, including HCTZ, can be effective in reducing blood pressure in patients with CKD, even in those with an estimated glomerular filtration rate (eGFR) below 50 ml/min/1.73m(2) 5.

Safety and Efficacy of HCTZ

• The safety and efficacy of HCTZ in patients with CKD depend on various factors, including the dose and duration of treatment, as well as the presence of other comorbidities 7, 6.
• Close monitoring of electrolyte levels and kidney function is necessary when using HCTZ in patients with CKD, as electrolyte abnormalities and changes in kidney function can occur 6.
• More research is needed to fully understand the effects of HCTZ on kidney function and to determine the optimal dose and duration of treatment for patients with CKD 3, 6.