Hydrochlorothiazide does not reduce the risk of kidney stone recurrence (NOSTONE)

Reference

Dhayat NA, Bonny O, Roth B, et al. Hydrochlorothiazide and prevention of kidney-stone recurrence. N Engl J Med 2023;388(9):781-791.

Synopsis

Thiazide diuretics like hydrochlorothiazide (HCTZ) have long been recommended as a way to prevent the recurrence of kidney stones, presumably by reducing the excretion of calcium. However, previous studies that found a benefit had significant methodologic shortcomings. This trial randomized 416 adults with at least 2 episodes of calcium-containing kidney stones in the past 10 years to receive placebo, HCTZ 12.5 mg, HCTZ 25 mg, or HCTZ 50 mg, each given once daily. Groups were balanced at baseline and the median duration of follow-up was 2.9 years. The median age of participants was 49 years, 99% were white, 20% were women, and most had experienced 2 or 3 episodes of stones in the past 10 years. Enrolled patients had previous stones that were at least 50% calcium oxalate, calcium phosphate, or a mixture of both. The rate of nonadherence (missing more than 20% of assigned doses) was 23% overall and did not vary substantially among the groups. At the end of the study period, 59% of participants had experienced a symptomatic or radiologic stone, but there was no difference among groups. Although there was a small reduction in radiologic recurrence for the 25 mg and 50 mg dose groups (32% and 34% vs 45% for 12.5 mg and 49% for placebo), there was no difference in symptomatic recurrences. Patients assigned to HCTZ (especially the higher doses) were more likely to experience hypokalemia, gout, or new-onset diabetes mellitus.