Hydrochlorothiazide was not superior to placebo in preventing recurrence of kidney stones, according to the findings of the NOSTONE trial published in the New England Journal of Medicine.¹

In this randomized placebo-controlled trial, investigators examined the efficacy of hydrochlorothiazide in preventing recurrence of calcium-containing kidney stones compared to placebo. The composite of symptomatic or radiologic recurrence of kidney stones as seen on CT scan was the primary endpoint of the study. For this, they selected 416 patients, from March 2017 to October 2019, who had had recurrent calcium-containing kidney stones in the preceding decade. They were randomized to receive 12.5 mg, 25 mg, 50 mg of hydrochlorothiazide or placebo once daily. The participants were aged 49 years (median) and majority (80%) were men.

Over a follow-up period of nearly 3 years, recurrence of symptomatic or radiologic nephrolithiasis occurred in 59% (62/105) patients on 12.5 mg hydrochlorothiazide vs 59% (60/102) in the placebo recipients. The recurrence occurred in 56% (61/108) patients on 25 mg hydrochlorothiazide vs 49% (49/101) patients who received 50 mg hydrochlorothiazide. The prevalence of adverse effects such as gout, incident type 2 diabetes, skin allergy, hypokalemia and increased serum creatinine levels was higher among those taking hydrochlorothiazide than in those on placebo.

Thiazide and thiazide-like diuretics have been widely used to prevent recurrence of kidney stones. However, findings of this study show no advantage of hydrochlorothiazide in preventing recurrence with different doses of the drug. Moreover, patients on hydrochlorothiazide also experienced more adverse effects. It is still uncertain whether these observations will influence clinical practice. Larger studies are required, according to the authors, to further evaluate the role of thiazides in preventing kidney stone recurrence.

Reference

Dhayat NA, et al. Hydrochlorothiazide and prevention of kidney-stone recurrence. N Engl J Med. 2023 Mar 2;388(9):781-791. doi: 10.1056/NEJMoa2209275