Should Hydrochlorothiazide (HCTZ) be added to the management of patients with diabetes and kidney disease?

From the Guidelines

Hydrochlorothiazide (HCTZ) is generally not recommended for patients with diabetes and kidney disease, particularly those with moderate to severe kidney dysfunction. For patients with diabetes and kidney disease, other antihypertensive medications like ACE inhibitors (such as lisinopril) or ARBs (such as losartan) are preferred first-line agents as they provide both blood pressure control and kidney protection 1. If additional blood pressure management is needed, calcium channel blockers or beta-blockers would typically be added before considering thiazide diuretics. HCTZ becomes less effective when kidney function declines (eGFR <30 mL/min/1.73m²), and it can worsen glucose control, increase uric acid levels, and potentially accelerate kidney function decline in these vulnerable patients. Loop diuretics like furosemide are generally more effective for fluid management in patients with reduced kidney function. Additionally, HCTZ can increase the risk of electrolyte abnormalities, particularly hyponatremia and hypokalemia, which may be more problematic in patients with diabetic kidney disease who may already have electrolyte imbalances.

Some key points to consider in the management of patients with diabetes and kidney disease include:

• The use of ACE inhibitors or ARBs as first-line agents for blood pressure control and kidney protection 1
• The consideration of calcium channel blockers or beta-blockers as additional agents for blood pressure management if needed
• The potential risks and limitations of using HCTZ in patients with moderate to severe kidney dysfunction, including decreased effectiveness and increased risk of electrolyte abnormalities
• The importance of monitoring kidney function and electrolyte levels in patients with diabetic kidney disease, particularly when using diuretics like HCTZ 1.

It's also worth noting that recent guidelines and studies have emphasized the importance of comprehensive and multidisciplinary care for patients with diabetes and kidney disease, including lifestyle interventions, pharmacotherapy, and regular monitoring of kidney function and other health outcomes 1.

From the FDA Drug Label

WARNINGS ... Diabetes and Hypoglycemia: Latent diabetes mellitus may become manifest and diabetic patients given thiazides may require adjustment of their insulin dose.

Renal Disease: Cumulative effects of the thiazides may develop in patients with impaired renal function. In such patients, thiazides may precipitate azotemia.

Hydrochlorothiazide (HCTZ) should be used with caution in patients with diabetes and kidney disease. The FDA drug label warns that thiazides, such as HCTZ, may precipitate azotemia in patients with impaired renal function and may require adjustment of insulin dose in diabetic patients. There is no direct evidence to support the addition of HCTZ to the management of patients with diabetes and kidney disease. In fact, the label suggests that HCTZ may exacerbate renal disease and worsen glycemic control. Therefore, HCTZ should not be added to the management of patients with diabetes and kidney disease without careful consideration of the potential risks and benefits 2.

From the Research

Addition of HCTZ to Management of Diabetic Patients with Kidney Disease

• The use of Hydrochlorothiazide (HCTZ) in patients with diabetes and kidney disease has been studied in various clinical trials 3, 4, 5, 6, 7.
• A study published in 2015 found that the addition of HCTZ to loop diuretics improved blood pressure levels and decreased proteinuria in patients with type 2 diabetic kidney disease 3.
• Another study published in 2016 found that the addition of HCTZ to angiotensin receptor blocker therapy achieved a lower sodium balance without accelerating the intrarenal renin-angiotensin system in patients with chronic kidney disease 4.
• However, a meta-analysis published in 2016 found that HCTZ treatment induced metabolic effects in type 2 diabetes, including increased fasting glucose and HbA1c, and decreased high-density lipoprotein-cholesterol 7.

Renoprotective Effects of HCTZ

• The renoprotective effects of HCTZ have been observed in several studies, including a study published in 2015 that found that the combination of HCTZ and loop diuretics improved blood pressure levels and decreased proteinuria in patients with type 2 diabetic kidney disease 3.
• Another study published in 2012 found that angiotensin II receptor blocker-based combination therapy, including HCTZ, was preferred for blood pressure control in hypertensive patients with diabetic and non-diabetic renal impairment 5.

Potential Side Effects of HCTZ

• The potential side effects of HCTZ, including metabolic effects, have been observed in several studies, including a meta-analysis published in 2016 that found that HCTZ treatment induced metabolic effects in type 2 diabetes 7.
• However, a study published in 1999 found that treatment with HCTZ and amiloride was well tolerated and did not have any significant side effects in patients with nephrogenic diabetes insipidus 6.