Does lisinopril (angiotensin-converting enzyme inhibitor) lower uric acid levels in patients with hyperuricemia?

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Does Lisinopril Lower Uric Acid Levels?

Lisinopril does not significantly lower uric acid levels in patients with hyperuricemia, and when combined with hydrochlorothiazide, it may actually increase uric acid levels due to the diuretic component.

Evidence for ACE Inhibitors and Uric Acid

The angiotensin-converting enzyme (ACE) inhibitors captopril, enalapril, and ramipril have been shown to mildly increase uricosuria by lowering net reabsorption of uric acid in the proximal tubule 1. However, the clinical effect of lisinopril on uric acid levels is minimal and not sufficient to treat hyperuricemia 1.

Key Findings on Lisinopril Specifically

  • When lisinopril is used alone, it does not significantly affect serum uric acid levels 2
  • When combined with hydrochlorothiazide, serum uric acid levels actually increase significantly (p < 0.05) due to the diuretic's effect 2
  • ACE inhibitors including lisinopril can blunt the rise in uric acid provoked by diuretics only when used at sufficiently high doses relative to the diuretic dose 1

Comparison with Other Antihypertensive Agents

Agents That Raise Uric Acid

  • Diuretics significantly elevate serum uric acid by increasing net uric acid reabsorption in the proximal tubule, starting at low doses (e.g., 12.5 mg hydrochlorothiazide) 1, 3
  • Beta-blockers tend to elevate serum uric acid and reduce glomerular filtration rate 1, 3
  • Alpha-1 blockers raise serum uric acid levels, particularly in men 3

Agents That Lower Uric Acid

  • Losartan is the only angiotensin receptor blocker that augments uricosuria and decreases serum uric acid 1, 4, 5
  • The American College of Rheumatology recommends choosing losartan preferentially as an antihypertensive agent for patients with gout due to its unique uric acid-lowering properties 6
  • In a direct comparison, losartan reduced uric acid from 0.44 to 0.39 mmol/L over 24 weeks, while candesartan increased it from 0.46 to 0.48 mmol/L (p = 0.01) 5

Neutral Agents

  • Calcium channel blockers do not increase serum uric acid levels 3
  • Other ACE inhibitors and angiotensin receptor blockers (excluding losartan) do not significantly increase serum uric acid 3

Clinical Recommendations

For hypertensive patients with hyperuricemia or gout:

  • Choose losartan as the preferred antihypertensive agent if an angiotensin system blocker is indicated 6
  • Avoid diuretics, beta-blockers, and alpha-1 blockers as they worsen hyperuricemia 3
  • If lisinopril is already prescribed and hyperuricemia develops, consider switching to losartan rather than adding urate-lowering therapy 5
  • Calcium channel blockers are acceptable alternatives that do not affect uric acid levels 3

Important Caveats

  • Multiple regression analysis confirms that diuretics and beta-blockers significantly contribute to hyperuricemia in patients on antihypertensive medication 3
  • The combination of lisinopril with hydrochlorothiazide will increase uric acid levels due to the diuretic component, negating any potential mild uricosuric effect of the ACE inhibitor 2
  • Gender differences exist in the effects of beta-blockers and alpha-1 blockers on uric acid metabolism 3

References

1
Research

Cardiovascular drugs and serum uric acid.

Cardiovascular drugs and therapy, 2003

6
Guideline

Telmisartan and Uric Acid Levels

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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