Background and Aims

Proton pump inhibitors (PPIs) are widely prescribed and have effects on gut ion absorption and urinary ion concentrations. PPIs might therefore protect against or contribute to development of kidney stones. We investigated the association between PPI use and kidney stones.

Methods

We performed a retrospective study using data from the Women’s Veteran’s Cohort Study, which comprised men and women, from October 1, 1999 through September 30, 2017. We collected data from 465,891 patients on PPI usage over time, demographics, laboratory results, comorbidities, and medication usage. Time-varying Cox proportional hazards and propensity matching analyses determined risk of PPI use and incident development of kidney stones. Use of histamine-2 receptor antagonists (H2RAs) was measured and levothyroxine use was a negative control exposure.

Results

PPI use was associated with kidney stones in the unadjusted analysis, with PPI use as a time-varying variable (hazard ratio [HR], 1.74; 95% CI, 1.67–1.82), and persisted in the adjusted analysis (HR, 1.46; CI, 1.38–1.55). The association was maintained in a propensity score-matched subset of PPI users and nonusers (adjusted HR, 1.25; CI 1.19–1.33). Increased dosage of PPI was associated with increased risk of kidney stones (HR, 1.11; CI, 1.09–1.14 for each increase in 30 defined daily doses over a 3-month period). H2RAs were also associated with increased risk (adjusted HR, 1.47; CI 1.31–1.64). We found no association, in adjusted analysis, of levothyroxine use with kidney stones (adjusted HR, 1.06; CI 0.94–1.21).

Conclusions

In a large cohort study of veterans, we found PPI use to be associated with a dose-dependent increase in risk of kidney stones. H2RA use also has an association with risk of kidney stones, so acid suppression might be an involved mechanism. The effect is small and should not change prescribing for most patients.

中文翻译：

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使用质子泵抑制剂会增加发生肾结石的风险。

背景和目标

质子泵抑制剂 (PPI) 被广泛使用，对肠道离子吸收和尿离子浓度有影响。因此，PPI 可能会预防或促进肾结石的形成。我们调查了 PPI 使用与肾结石之间的关联。

方法

我们使用 1999 年 10 月 1 日至 2017 年 9 月 30 日期间女性退伍军人队列研究的数据进行了一项回顾性研究。我们从 465,891 名患者中收集了有关 PPI 使用情况、人口统计学、实验室结果、合并症、和药物使用。时变 Cox 比例风险和倾向匹配分析确定了 PPI 使用和肾结石事件发展的风险。测量了组胺-2 受体拮抗剂 (H2RA) 的使用，左旋甲状腺素的使用是一种阴性对照暴露。

结果

在未经调整的分析中，PPI 的使用与肾结石相关，PPI 的使用作为一个时变变量（风险比 [HR]，1.74；95% CI，1.67-1.82），并在调整后的分析中持续存在（HR，1.46； CI，1.38-1.55）。该关联在 PPI 用户和非用户的倾向得分匹配子集中保持（调整后的 HR，1.25；CI 1.19-1.33）。PPI 剂量的增加与肾结石风险的增加有关（HR，1.11；CI，1.09-1.14，在 3 个月内每增加 30 次定义的每日剂量）。H2RA 也与风险增加有关（调整后的 HR，1.47；CI 1.31-1.64）。在调整后的分析中，我们发现左旋甲状腺素的使用与肾结石没有关联（调整后的 HR，1.06；CI 0.94-1.21）。

结论

在一项针对退伍军人的大型队列研究中，我们发现 PPI 的使用与肾结石风险的剂量依赖性增加有关。H2RA 的使用也与肾结石的风险有关，因此抑酸可能是一种涉及的机制。效果很小，不应改变大多数患者的处方。