Evidence map›Paper›PMID 41849060›Full record

ArticleInternational urology and nephrology2026

Genetic causal association between kidney stones and proton pump inhibitors.

Yaohui Jiang, Lede Lin, Chao Cheng, Liang Zhou

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Article in International urology and nephrology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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4 authors.

Yaohui Jiang *Department of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Lede Lin *Department of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Chao ChengDepartment of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Liang ZhouDepartment of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China. zhouliang1990@scu.edu.cn.

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6 · The paper itself

Abstract

purposeKidney stone disease is a common metabolic disorder with high recurrence rates and an associated risk of chronic kidney disease, while proton pump inhibitors (PPIs) are widely used medications with potential links to renal complications. Previous observational studies have suggested an association between PPI use and kidney stones, but the causal relationship remains unclear. This study aimed to investigate the causal effect of PPIs on kidney stones using the Mendelian randomization (MR) analysis.

methodsWe utilized large-scale genome-wide association study (GWAS) data to construct genetic instruments for PPI use (including esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) from the UK Biobank, with kidney stone outcomes derived from the FinnGen Consortium. Additionally, a drug target MR (DTMR) analysis was performed using genetic proxies of the H⁺/K⁺-ATPase (encoded by ATP4A and ATP4B), the core target of PPIs. Five MR models were applied to assess causality, with sensitivity analyses to validate robustness.

resultsThe results showed no significant causal association between genetically predicted PPIs use and kidney stone risk (esomeprazole: OR = 0.99, 95% CI 0.90-1.09, p = 0.884; lansoprazole: OR = 1.04, 95% CI 0.92-1.17, p = 0.559; omeprazole: OR = 1.03, 95% CI 0.91-1.17, p = 0.628; rabeprazole: OR = 1.02, 95% CI 0.99-1.05, p = 0.088; pantoprazole: OR = 1.01, 95% CI 0.97-1.05, p = 0.687). DTMR analysis also revealed no significant association between genetic proxies of ATP4A/ATP4B and kidney stones across multiple sensitivity thresholds.

conclusionIn conclusion, this study found no evidence supporting a causal role for PPIs in increasing kidney stone risk, providing genetic-level evidence to support the safe use of PPIs in patients with gastric ulcers or gastroesophageal reflux disease.

Indexed as

H(+)-K(+)-Exchanging ATPaseKidney CalculiProton Pump InhibitorsEsomeprazoleGenome-Wide Association StudyHumansLansoprazoleMendelian Randomization AnalysisOmeprazolePantoprazoleRabeprazoleEsomeprazoleH(+)-K(+)-Exchanging ATPaseLansoprazoleOmeprazolePantoprazoleProton Pump InhibitorsRabeprazoleGenome-wide association studyKidney stonesMendelian randomizationProton pump inhibitors

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.