Can chlorthalidone (a diuretic) cause hyperuricemia (elevated uric acid levels)?

Chlorthalidone Does Cause Hyperuricemia

Yes, chlorthalidone definitively causes hyperuricemia as a known and well-documented adverse effect. 1 This is clearly established in clinical guidelines and drug information.

Mechanism and Evidence

Chlorthalidone, a thiazide-like diuretic, increases serum uric acid levels through several mechanisms:

• Decreases uric acid secretion in the renal tubules
• Increases uric acid reabsorption
• Creates competition for the same transport mechanisms in the kidney 2

The FDA drug label for chlorthalidone explicitly states: "Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving chlorthalidone." 1

Clinical Significance and Magnitude

The effect of chlorthalidone on uric acid levels is dose-dependent:

• Higher doses (≥50 mg daily) cause greater increases in serum uric acid (approximately 90 μmol/L or 1.5 mg/dL) 3
• Lower doses (≤25 mg daily) cause more modest increases (approximately 45 μmol/L or 0.75 mg/dL) 3
• In one study, reducing chlorthalidone from 50 mg daily to 50 mg three times weekly significantly decreased serum urate levels while maintaining most of the antihypertensive effect 4

Monitoring and Management

When prescribing chlorthalidone, the following approach is recommended:

1. Baseline assessment: Check serum uric acid levels before initiating therapy, especially in patients with risk factors for gout
2. Monitoring: Periodically monitor serum uric acid levels after starting chlorthalidone 3
3. Dose consideration: Use the lowest effective dose to minimize hyperuricemia 4
4. Risk assessment: Recognize that patients with pre-existing elevated uric acid levels are at higher risk for developing gout

Clinical Context and Outcomes

Despite causing hyperuricemia, several important points should be considered:

• The ALLHAT trial showed that chlorthalidone's cardiovascular benefits outweighed the risks of metabolic effects in most patients 5
• Hyperuricemia from chlorthalidone rarely progresses to clinical gout (only 15 cases among 3,693 participants over 5 years in the Hypertension Detection and Follow-up Program) 6
• Current guidelines acknowledge the hyperuricemic effect but still recommend thiazide-like diuretics as first-line agents for hypertension in most patients 5

Special Considerations

Exercise particular caution when using chlorthalidone in:

• Patients with a history of gout
• Patients with baseline hyperuricemia
• Patients taking other medications that can increase uric acid levels
• Patients with impaired renal function

Conclusion

Chlorthalidone consistently causes hyperuricemia, but the clinical significance varies by patient. The risk of developing symptomatic gout is relatively low compared to the cardiovascular benefits of the medication in most hypertensive patients.