For decades, hydrochlorothiazide (HCTZ) has been recommended to prevent kidney stone recurrence in patients with calcium stones. A recent study published in the New England Journal of Medicine
calls this long-standing guidance into question. The NOSTONE trial randomized 416 adults with a history of two or more calcium stones to three doses of once-daily HCTZ (12.5 mg, 25 mg, 50 mg) or placebo. The primary outcome was a composite of symptomatic or radiologic stone recurrence. After a median follow-up of 2.9 years, there was no significant difference between any of the treatment arms (59%, 56%, 49%, 59%, respectively).
The results of this study are surprising given that HCTZ reduces urinary calcium concentrations, and theoretically, this should suppress stone formation. The authors note that supersaturation ratios for calcium oxalate and calcium phosphate - measures associated with stone formation - were unchanged in the HCTZ groups, possibly explaining the overall lack of efficacy.