#VisualAbstract: Hydrochlorothiazide does not impact risk of kidney-stone recurrence

1. In this randomized controlled trial, among patients with recurrent kidney stones, hydrochlorothiazide did not alter the risk of symptomatic or radiographic stone recurrence.

2. Hydrochlorothiazide was associated with an increased risk of adverse events as compared to placebo.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Kidney stones are a common medical condition. In many patients, these stones can be recurrent, resulting in significant distress, impaired quality of life, and healthcare burden. Calcium oxalate and calcium phosphate comprise the most common forms of kidney stones, and hypercalciuria is the most common metabolic disturbance predisposing patients to kidney stones. Thiazides, namely hydrochlorothiazide, are diuretic agents that have been utilized to prevent a recurrence, with limited evidence only supporting higher doses that are associated with higher risks of adverse events. The current study was a randomized placebo-controlled trial to investigate the efficacy and safety of hydrochlorothiazide, at 12.5mg, 25mg, and 50mg, in preventing symptomatic or radiographic recurrence of kidney stones in susceptible patients. None of the doses resulted in significant changes in the risk of stone recurrence compared to the placebo. The hydrochlorothiazide-treated patients were more likely to develop side effects, including gout and new-onset diabetes. The trial was limited by demographic underrepresentation and a short median follow-up of 2.9 years. However, overall, these results showed that hydrochlorothiazide did not differ significantly from placebo in the prevention of kidney stone recurrence in patients at high risk.

Click here to read the study in NEJM

In-Depth [randomized controlled trial]: The current study was a randomized controlled trial to assess the efficacy of hydrochlorothiazide in preventing kidney stone recurrence. Patients aged 18 or older who had at least two episodes of kidney stones in the preceding ten years were included. Exclusion criteria included secondary nephrolithiasis and medications interfering with kidney stone formation. The primary outcome was a composite of symptomatic or radiologic recurrence of kidneys, identified via regular follow-ups every three months or via low-dose computed tomographic study. Overall, 416 patients were randomized 1:1:1:1 to receive hydrochlorothiazide at 12.5mg, 25mg, or 50mg, or placebo once daily. The median follow-up was 2.9 years. The primary outcome occurred in 60 of 102 patients (59%) in the placebo group, in 62 of 105 (59%) in those receiving 12mg hydrochlorothiazide (Rate Ratio [RR] 1.33; 95% Confidence Interval [CI] 0.92 to 1.93), in 61 of 108 patients receiving 25mg hydrochlorothiazide (RR 1.24; 95% CI 0.86 to 1.79), and in 49 of 101 patients receiving 50mg hydrochlorothiazide (RR 0.92; 95% CI 0.63 to 1.36). The 25mg- and 50 mg-hydrochlorothiazide groups were associated with lower radiographic recurrence rates. Notably, compared to placebo, patients treated with hydrochlorothiazide were more likely to develop new-onset diabetes mellitus, hypokalemia, gout, skin allergy, and high plasma creatinine level from baseline. These results suggest that hydrochlorothiazide may not effectively prevent kidney stone recurrence in susceptible patients.

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