From the Guidelines
Chlorthalidone can potentially worsen Acute Kidney Injury (AKI) and should generally be avoided in patients with AKI or at high risk for developing it. As a thiazide-like diuretic, chlorthalidone reduces blood volume and blood pressure by increasing urinary excretion of sodium and water, which can decrease renal perfusion. In the setting of AKI, where kidney function is already compromised, chlorthalidone may further reduce kidney blood flow, exacerbate pre-renal azotemia, and delay recovery from kidney injury. Additionally, chlorthalidone can cause electrolyte abnormalities such as hypokalemia and hyponatremia, which may complicate management of AKI.
Some key points to consider when using chlorthalidone in patients with or at risk for AKI include:
- Monitoring for hyponatremia and hypokalemia, uric acid and calcium levels 1
- Using with caution in patients with history of acute gout unless patient is on uric acid–lowering therapy 1
- Avoiding use in combination with ARBs or direct renin inhibitor 1
- Being aware of the increased risk of hyperkalemia, especially in patients with CKD or in those on K+ supplements or K+-sparing drugs 1
- Recognizing the risk of acute renal failure in patients with severe bilateral renal artery stenosis 1
For patients with AKI, medication management typically involves temporarily discontinuing diuretics like chlorthalidone, correcting volume status, addressing the underlying cause of kidney injury, and monitoring kidney function and electrolytes closely. Once kidney function stabilizes and improves, a careful reassessment should determine if and when chlorthalidone can be safely reintroduced, often at a lower dose with close monitoring. The most recent and highest quality study, 1, supports the use of chlorthalidone with caution in patients with CKD, but emphasizes the importance of monitoring renal function and electrolytes.
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 use of chlorthalidone may worsen Acute Kidney Injury (AKI) in patients with severe renal disease or impaired renal function, as it may precipitate azotemia.
- Key points:
- Use with caution in severe renal disease
- May precipitate azotemia in patients with renal disease
- Cumulative effects may develop in patients with impaired renal function 2
From the Research
Acute Kidney Injury (AKI) and Chlorthalidone
- AKI is defined by a sudden loss of excretory kidney function, and its management in critical care settings is challenging 3.
- The use of diuretics, including chlorthalidone, in AKI has been studied, with some evidence suggesting that diuretics may be ineffective and even detrimental in the prevention and treatment of AKI 4, 5.
- Chlorthalidone has been shown to be effective in reducing blood pressure in patients with chronic kidney disease (CKD) and treatment-resistant hypertension, but its use may be associated with adverse effects such as hypokalemia, hyperuricemia, and reversible increases in serum creatinine 6, 7.
Potential Risks of Chlorthalidone in AKI
- Diuretics, including chlorthalidone, may worsen AKI by causing hypotension, reducing renal medullary oxygenation, and increasing the risk of hyperkalemia 4, 5.
- The use of chlorthalidone in patients with AKI may require careful monitoring of serum creatinine, potassium levels, and blood pressure to minimize the risk of adverse effects 6, 7.
Current Evidence and Recommendations
- The current evidence suggests that diuretics, including chlorthalidone, should not be used to prevent or treat AKI, but rather to manage volume overload and symptoms of pulmonary edema 4, 5.
- Further studies are needed to determine the safety and efficacy of chlorthalidone in patients with AKI and CKD, and to establish clear guidelines for its use in these populations 6, 7.