Are PPIs associated with CKD?
PPIs are widely used and maintain a fairly good safety profile; however, recent observational evidence has described an association of PPI use with a variety of risks, including hip fractures, cardiovascular events, pneumonia, Clostridium difficile infection, and most recently CKD and end-stage kidney disease (ESKD). Higher-dose PPI use was associated with a greater incident risk of CKD, an association that remained significant with a time-varying model. The duration of PPI use was also significantly associated with incident CKD and ESKD. One can hypothesize that CKD and ESKD occurring in the setting of chronic PPI use is due to unrecognized (and untreated) AIN, which then transitions into chronic interstitial nephritis. However, little is known beyond the epidemiological observation of association. Therefore the precise mechanism as well as whether PPI therapy itself is causative is unclear.