Hydrochlorothiazide shows little improvement in kidney stone recurrence

The incidence of kidney stone recurrence did not significantly differ among patients who received hydrochlorothiazide compared with those who received placebo, according to a study published in The New England Journal of Medicine.

Nasser A. Dhayat, MD, of the departments of nephrology and hypertension at the University of Bern in Switzerland, and colleagues wrote that previous studies have suggested thiazide and thiazide-like diuretic agents — particularly hydrochlorothiazide — “effectively prevent the recurrence of stones.”

“However, previous studies have had methodologic limitations such as inadequate concealment of treatment assignment, a lack of double-blinding, a lack of an intention-to-treat analysis, the use of outdated dietary recommendations, and the use of imaging methods with low sensitivity and specificity,” they wrote. “Furthermore, only high

doses of thiazides were studied; such dose levels are known to increase the risk of adverse effects.”

Dhayat and colleagues conducted a double-blind, randomized, placebo-controlled trial to determine the efficacy of hydrochlorothiazide in preventing kidney stone recurrence. The researchers randomly assigned 416 patients (median age, 49 years; 80% men) to either 12.5 mg (n = 105), 25 mg (n = 108) or 50mg (n = 101) of hydrochlorothiazide, or placebo (n = 102). The patients had a clinical follow-up 3 months after randomization and then every year afterwards for a maximum of 3 years.

The study’s primary endpoint event was the composite of symptomatic or radiologic recurrence of kidney stones. Symptomatic recurrence was defined as stones that clearly passed or needed surgical removal, while radiologic recurrence was defined as new stones that appeared on CT scans or the enlargement of stones previously identified at baseline.

Dhayat and colleagues found that a primary endpoint event occurred in:

• 59% of patients in the placebo group;
• 59% of patients in the 12.5 mg hydrochlorothiazide group (RR = 1.33; 95% CI, 0.92-1.93);
• 56% of patients in the 25 mg hydrochlorothiazide group (RR = 1.24; 95% CI, 0.86-1.79); and
• 49% of patients in the 50 mg hydrochlorothiazide group (RR = 0.92; 95% CI, 0.63-1.36).

Additionally, the researchers found that new onset diabetes mellitus, gout, skin allergy, hypokalemia and a plasma creatinine level that surpassed 150% of the baseline levels were more frequent in patients in the hydrochlorothiazide groups than those assigned placebo.

“The differences in citrate and oxalate excretion between the hydrochlorothiazide groups and the placebo group may have counteracted the observed lower urinary calcium excretion that was induced by hydrochlorothiazide, thus resulting in no evident differences among patients receiving hydrochlorothiazide and those receiving placebo with respect to relative supersaturation ratios,” the researchers wrote.

Dhayat and colleagues noted several limitations to the study, including an underrepresentation of women and races, and the shorter duration of the follow-up, which may have affected hydrochlorothiazide effect.

“Whether our results also apply to longer-acting thiazides remains to be determined,” Dhayat and colleagues concluded.