No Reduction in Recurrent Kidney Stones with Hydrochlorothiazide

Full access

In patients with recurring kidney stones, hydrochlorothiazide does not reduce the incidence of further recurrences compared with placebo, reports a clinical trial in The New England Journal of Medicine.

The trial enrolled 416 adult patients with recurrent kidney stones with at least two episodes over the past 10 years and any previous stone containing at least 50% calcium oxalate and/or calcium phosphate. Patients were randomly assigned to receive once-daily hydrochlorothiazide at a dose of 12.5, 25, or 50 mg or placebo. A primary composite end point of symptomatic or radiologic kidney stone recurrence was evaluated at a median follow-up of 2.9 years.

No dose of hydrochlorothiazide was effective in reducing the risk of recurrent kidney stones. Compared with the 59% incidence with placebo, recurrence rates with hydrochlorothiazide were 59% at the 12.5-mg dose, 56% at the 25-mg dose, and 49% at the 50-mg dose. The symptomatic recurrence rate was similar across groups, with a 34% rate in the placebo group. The radiologic recurrence rate—a composite of stone growth or new stone formation—was lowest in the hydrochlorothiazide 25- and 50-mg dose groups.

Patients receiving hydrochlorothiazide had higher rates of hypokalemia, gout, new-onset diabetes, skin allergy, and plasma creatinine >150% of baseline. Serious adverse events were no more common with hydrochlorothiazide versus placebo.

Kidney stones are a common and frequently recurrent problem. Hydrochlorothiazide is widely prescribed to prevent recurrent stones, despite limitations of the research on this issue.

This randomized, placebo-controlled trial finds no significant reduction in the frequency of recurrent kidney stones in high-risk patients taking hydrochlorothiazide. This is so across the range of once-daily doses studied. The researchers note the lack of effectiveness despite decreased urinary calcium excretion in the hydrochlorothiazide group [Dhayat NA, et al. Hydrochlorothiazide and prevention of kidney-stone recurrence. N Engl J Med 2023; 388:781–791. doi: 10.1056/NEJMoa2209275].