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Use of Proton Pump Inhibitors Increases Risk of Incident Kidney Stones

Simonov M, Abel EA, Skanderson M, Masoud A, Hauser RG, Brandt CA, Wilson FP, Laine L

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2021

465,891 participants · 17 citations

Abstract

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,…

How strong is the evidence?

Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 465,891 participants or records.

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