Proton Pump Inhibitor Use, CYP2C19 genotypes, and Subsequent Incidence of Chronic Kidney Disease

Background The widespread use of proton pump inhibitors (PPIs) has generated concerns about side effects Numerous studies have suggested that PPIs use may increase the risk of kidney disease. In particular, it is unclear whether genotype of the CYP2C19 enzyme system, the main metabolic pathway of PPIs, modifies the association between PPIs and the development of chronic kidney disease (CKD) or end-stage kidney disease (ESKD). Methods This was a prospective cohort study of white European participants from the UK Biobank. CKD and ESKD were determined by ICD-10 coding. Self-reported PPI use was recorded using an electronic questionnaire and confirmed by trained staff. The CYP2C19 genotype is defined by two of the most common CYP2C19 functional polymorphisms (rs4244285 and rs12248560). Multivariable Cox proportional hazards regression models were used to assess the associations of PPIs with incident CKD or ESKD. Results A total of 419670 participants were included in the study, of which 39,493 participants were PPIs users. Compared with non-user, PPI users had a significantly higher risk of developing CKD (HR 1.408, CI 1.352–1.467) and ESKD (HR 1.288, CI 1.03–1.609). This association persisted in sensitivity analyses. However, there was no significant difference in the risk of developing CKD among participants taking PPIs between the different CYP2C19 genotypes. Conclusion The use of PPIs was associated with the risks of developing CKD and ESKD. There was no evidence supporting the CYP2C19 genotype as a moderator on the relationship between PPIs and kidney diseases.