Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence
In the NOSTONE randomized trial, hydrochlorothiazide at doses up to 50 mg daily was not significantly better than placebo at preventing recurrence of calcium-containing kidney stones, challenging a 40-year cornerstone of stone prophylaxis.
Background
Nephrolithiasis is among the most common kidney conditions and carries a high recurrence risk. Thiazide diuretics have been used for decades to prevent recurrence of calcium-containing stones, but placebo-controlled and dose-response data have been limited, leaving the true efficacy and optimal dose uncertain.
Study design
NOSTONE was a double-blind, multicenter, placebo-controlled trial that randomized 416 patients with recurrent calcium-containing kidney stones to hydrochlorothiazide 12.5 mg, 25 mg, or 50 mg once daily, or placebo. Patients were followed for a median of 2.9 years. The primary endpoint was a composite of symptomatic or radiologic stone recurrence, with a focus on dose-response.
Key findings
A primary-endpoint event occurred in 59% of the placebo group versus 59%, 56%, and 49% in the 12.5 mg, 25 mg, and 50 mg hydrochlorothiazide groups, respectively, with no significant dose-response relationship (P = 0.66). Rate ratios versus placebo were not significant at any dose. Hypokalemia, gout, new-onset diabetes, skin allergy, and a rise in plasma creatinine were more common with hydrochlorothiazide than with placebo.
Clinical implications
These results suggest hydrochlorothiazide may not meaningfully reduce stone recurrence across the doses tested, and treatment carries metabolic and other adverse effects. The findings argue for a more restrictive, individualized use of thiazides for stone prevention, though some commentators note the trial included patients without overt hypercalciuria, which may have attenuated the observed effect.
Category
Research
Source
New England Journal of Medicine
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