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Purpose <p>Thiazide (THZ) and thiazide-like (TL) diuretics are routinely prescribed and considered to be the gold-standard prophylaxis for kidney stones (KS) recurrence in current guidelines despite having limited evidence. Thus, we aimed to investigate the efficacy and safety of different doses of THZ and TL diuretics in preventing KS recurrence.</p> Methods <p>We searched for randomised controlled trials in PubMed, Web of Science, Embase, CENTRAL, and clinical trials registries from their inception through January 2025. The clinical or radiological KS recurrence was the primary endpoint, while the occurrence of adverse effects at any time was the secondary endpoint. We estimated odds ratio (OR) in a frequentist random-effects network meta-analysis with <i>P</i> &lt; 0.05. This study was prospectively registered (CRD42025650062).</p> Results <p>Nine trials (<i>n</i> = 999) were included. Chlorthalidone 50&#xa0;mg/d (OR: 0.18, 95% confidence interval [CI] 0.04–0.88), hydrochlorothiazide 50&#xa0;mg/d (OR: 0.52, CI 0.29–0.93), and trichlormethiazide 4&#xa0;mg/d (OR: 0.26, CI 0.10–0.68) were different from placebo in terms of KS recurrence. There was no evidence of dose-dependent effect when comparing hydrochlorothiazide 50&#xa0;mg/d to 12.5&#xa0;mg/d (OR: 0.58, CI 0.25–1.34) or 25&#xa0;mg/d (OR: 0.65, CI 0.28–1.48), nor comparing chlorthalidone 50&#xa0;mg/d to 25&#xa0;mg/d (OR: 0.80, CI 0.12–5.20). Only trichlormethiazide 4&#xa0;mg/d (OR: 49.96, CI 1.78–1 402.80) provoked more adverse effects than placebo.</p> Conclusion <p>Although some therapies were statistically different from placebo, the current evidence does not support their use in preventing KS recurrence due to several limitations, indicating that THZ and/or TL diuretics should not be routinely prescribed. Further well-designed trials are urgently needed to address head-to-head comparisons and provide high-quality evidence.</p>

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Thiazide and thiazide-like diuretics for kidney stones recurrence: a systematic review and network meta-analysis of randomised controlled trials

  • 期刊论文

  • 发表日期：

    2025年12月15日

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  • Alessandro V. Oliveira,
  • Ana Luiza N. Sampaio,
  • Rui W. Mascarenhas Jr.,
  • Luis Otávio A. D. Pinto,
  • Regis B. Andriolo

摘要

Purpose

Thiazide (THZ) and thiazide-like (TL) diuretics are routinely prescribed and considered to be the gold-standard prophylaxis for kidney stones (KS) recurrence in current guidelines despite having limited evidence. Thus, we aimed to investigate the efficacy and safety of different doses of THZ and TL diuretics in preventing KS recurrence.

Methods

We searched for randomised controlled trials in PubMed, Web of Science, Embase, CENTRAL, and clinical trials registries from their inception through January 2025. The clinical or radiological KS recurrence was the primary endpoint, while the occurrence of adverse effects at any time was the secondary endpoint. We estimated odds ratio (OR) in a frequentist random-effects network meta-analysis with P < 0.05. This study was prospectively registered (CRD42025650062).

Results

Nine trials (n = 999) were included. Chlorthalidone 50 mg/d (OR: 0.18, 95% confidence interval [CI] 0.04–0.88), hydrochlorothiazide 50 mg/d (OR: 0.52, CI 0.29–0.93), and trichlormethiazide 4 mg/d (OR: 0.26, CI 0.10–0.68) were different from placebo in terms of KS recurrence. There was no evidence of dose-dependent effect when comparing hydrochlorothiazide 50 mg/d to 12.5 mg/d (OR: 0.58, CI 0.25–1.34) or 25 mg/d (OR: 0.65, CI 0.28–1.48), nor comparing chlorthalidone 50 mg/d to 25 mg/d (OR: 0.80, CI 0.12–5.20). Only trichlormethiazide 4 mg/d (OR: 49.96, CI 1.78–1 402.80) provoked more adverse effects than placebo.

Conclusion

Although some therapies were statistically different from placebo, the current evidence does not support their use in preventing KS recurrence due to several limitations, indicating that THZ and/or TL diuretics should not be routinely prescribed. Further well-designed trials are urgently needed to address head-to-head comparisons and provide high-quality evidence.