Thiazides for kidney stone recurrence prevention

Abstract

Purpose of review: Kidney stones are the most common condition affecting the kidney, and characterized by a high rate of recurrence. Thiazide and thiazide-like diuretics (thiazides) are commonly prescribed to prevent the recurrence of kidney stones. This review offers a comprehensive up-to-date assessment of the evidence supporting the use of thiazides for kidney stone recurrence prevention, highlights potential harms associated with treatment, and identifies areas of knowledge that require further investigation.

Recent findings: The clinical routine to prescribe thiazides for kidney stone prevention has recently been challenged by the findings of the large NOSTONE trial that failed to show superiority of hydrochlorothiazide at doses up to 50 mg daily over placebo in preventing a composite of clinical or radiological recurrence in patients at high risk of recurrence. Yet, adverse events such as new onset diabetes mellitus and gout were more common in patients receiving hydrochlorothiazide compared to placebo. As demonstrated by a novel meta-analysis presented in this review encompassing all randomized placebo-controlled trials with thiazide monotherapy, current trial evidence does not indicate that thiazide monotherapy is significantly better than placebo in preventing kidney stone recurrence.

Summary: Given the limited efficacy and possible adverse effects, we advocate for a restrictive use of thiazides for kidney stone recurrence prevention. Clearly, there remains a high unmet medical need for effective, targeted therapies to prevent recurrence of kidney stones.

Box 1

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FIGURE 1

Random effects meta-analysis (using empirical Bayes (Paule Mandel) model with Knapp Hartung standard errors) of all placebo-controlled trials evaluating a thiazide (note: trials without placebo control or concomitant potassium supplementation were not considered). Size of squares is proportional to the weight of each trial in the meta-analysis with lines indicating the 95% confidence interval. The diamond shows the meta-analytic estimate with 95% confidence interval. The line indicates the 95% prediction interval. Heterogeneity statistics: τ² = 0.14, I² = 47%, H² = 1.89. CI, confidence interval; N, number; PY, patient years.