Hydrochlorothiazide no better than placebo for preventing kidney stone recurrence
A randomized, double-blind, placebo-controlled trial in Switzerland found that patients with a history of recurring kidney stones were no less likely to experience symptomatic or radiologic recurrence with hydrochlorothiazide versus placebo.
Patients with recurring kidney stones do not appear to benefit from treatment with hydrochlorothiazide, a new study found.
Researchers performed a randomized double-blind trial that assigned patients with recurrent calcium-containing kidney stones to receive hydrochlorothiazide at a dose of 12.5 mg, 25 mg, or 50 mg once daily or placebo once daily. All patients also received guideline-based dietary recommendations for kidney stone prevention. The study's main goal was to investigate the dose-response effect for the primary end point, a composite of symptomatic or radiologic recurrence of kidney stones. Radiologic recurrence was defined as the appearance of new stones on imaging or the enlargement of pre-existing stones on the baseline image. Patients had a follow-up visit three months after randomization, then yearly, along with a telephone visit every three months. The trial also assessed safety. Results were published March 2 by the New England Journal of Medicine.
Four hundred sixteen patients in Switzerland were randomized and followed for a median of 2.9 years. Median age was 49 years, and most (80%) were men. The median number of kidney stone events during the 10 years before randomization was three, with 139 patients (33%) reporting four or more kidney stone events in that time period. The primary end point occurred in 60 of 102 patients (59%) in the placebo group versus in 62 of 105 patients (59%) in the 12.5-mg hydrochlorothiazide group (rate ratio, 1.33; 95% CI, 0.92 to 1.93), 61 of 108 patients (56%) in the 25-mg group (rate ratio, 1.24; 95% CI, 0.86 to 1.79), and 49 of 101 patients (49%) in the 50-mg group (rate ratio, 0.92; 95% CI, 0.63 to 1.36). No relationship was observed between hydrochlorothiazide dose and occurrence of the primary end point (P=0.66). Hypokalemia, gout, new-onset diabetes, skin allergy, and a plasma creatinine level that exceeded 150% of the baseline level were more common in patients receiving hydrochlorothiazide.
The researchers noted that women and non-White patients were underrepresented in the trial and that the three-year follow-up period may not have been sufficient to detect a treatment effect in all cases. They said that differences in citrate and oxalate excretion between the hydrochlorothiazide groups and the placebo group may have counteracted the observed lower urinary calcium excretion induced by hydrochlorothiazide, leading to no evident treatment differences. “The results of our trial show that treatment with hydrochlorothiazide did not appear to differ substantially from placebo in preventing the recurrence of kidney stones in patients at high risk for recurrence,” they concluded.
An accompanying editorial noted that the last trials supporting thiazides for recurrent kidney stones were conducted almost 30 years ago, when higher doses were more common, and it said that while the current results are not yet practice-changing, they call into question use of thiazides for this indication and should prompt additional larger studies. “Regardless of the effectiveness of thiazides in the treatment of kidney stones, thiazide therapy clearly confers an array of frequent side effects, including hypokalemia, hyponatremia, hypercalcemia, hyperuricemia, dysglycemia, and dyslipidemia; the risk of such conditions prevents many patients from taking them,” the editorialist wrote. “Thus, it is time for new, more effective medical therapies with fewer side effects to be developed for this common, costly medical problem.”