From the Guidelines
Chlorthalidone 25 mg should be reduced to 12.5 mg daily or switched to HCTZ 25 mg daily to prevent further renal deterioration while maintaining blood pressure control, as recommended by 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 1. The patient's dehydration and significant GFR reduction from 60 to 40 can be attributed to the potency of chlorthalidone 25 mg, which is approximately 1.5-2 times more potent than hydrochlorothiazide (HCTZ) 25 mg. Key considerations for managing this patient include:
- Ensuring adequate hydration by maintaining fluid intake of at least 2 liters daily unless contraindicated
- Temporarily holding the diuretic during acute illness with decreased oral intake
- Close monitoring of renal function and follow-up within 1-2 weeks for electrolyte and renal function assessment
- Chlorthalidone has a longer half-life (40-60 hours versus 6-15 hours for HCTZ) and greater volume of distribution, resulting in more sustained diuretic effect and blood pressure control, but also increasing the risk of dehydration and electrolyte abnormalities, particularly in patients with borderline renal function 1. The GFR drop suggests the current dose is excessive for this patient's renal capacity, and dose adjustment is necessary to prevent further renal deterioration while maintaining blood pressure control, in line with the principles outlined in the guideline for the management of chronic heart failure in adults 1 and the consensus recommendations for sick day medication guidance for people with diabetes, kidney, or cardiovascular disease 1.
From the FDA Drug Label
Chlorthalidone should be used with caution in severe renal disease. In patients with renal disease, chlorthalidone or related drugs may precipitate azotemia. The AUC for hydrochlorothiazide is increased by 70 and 700% for patients with mild and moderate renal insufficiency, respectively.
The patient's drop in GFR from 60 to 40 with dehydration on chlorthalidone suggests that chlorthalidone may be more likely to precipitate azotemia in this patient compared to HCTZ.
- Chlorthalidone should be used with caution in patients with severe renal disease.
- HCTZ has a decreased renal clearance in patients with mild and moderate renal impairment. Given the patient's renal impairment, it is recommended to use HCTZ with caution and monitor renal function closely. 2 3
From the Research
Comparison of Chlorthalidone and HCTZ
- Chlorthalidone 25 mg and HCTZ 25 mg are both used to treat hypertension, but their effects on kidney function and cardiovascular events differ 4.
- A study found that chlorthalidone use was associated with a higher risk of eGFR decline and cardiovascular events compared to HCTZ use, particularly in patients with higher eGFR 4.
- Another study showed that chlorthalidone may reduce blood pressure in patients with moderate to advanced chronic kidney disease, but it also increased the risk of hypokalemia and other adverse events 5.
Effects on Kidney Function
- Chlorthalidone use was associated with a higher risk of eGFR decline of 30% or greater compared to HCTZ use, with a hazard ratio of 1.24 (95% CI, 1.13-1.36) 4.
- The risk of eGFR decline was more pronounced in patients with higher eGFR, suggesting that chlorthalidone may be more harmful to kidney function in patients with better baseline kidney function 4.
Cardiovascular Events
- Chlorthalidone use was associated with a higher risk of cardiovascular events, including myocardial infarction, coronary revascularization, heart failure, and atrial fibrillation, compared to HCTZ use 4.
- The hazard ratio for cardiovascular events was 1.12 (95% CI, 1.04-1.22) for chlorthalidone compared to HCTZ 4.
Dehydration and Kidney Function
- Dehydration can exacerbate kidney function decline, and chlorthalidone may increase the risk of dehydration due to its diuretic effects 5.
- A patient with a drop in GFR from 60 to 40 with dehydration on chlorthalidone may be at higher risk of further kidney function decline and cardiovascular events 4, 5.