Long-Term Proton Pump Inhibitor Use and the Risk of Kidney Disease, Dementia, and Fractures: A Systematic Review

Chronic use of proton pump inhibitors (PPIs), although effective for acid-related disorders, has raised concerns regarding their association with various long-term adverse health outcomes. This systematic review aimed to synthesize evidence from observational studies and meta-analyses evaluating the potential risks linked to prolonged PPI exposure, including cognitive decline, chronic kidney disease, bone fractures, and cardiovascular events. A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Embase, focusing on studies involving adult human populations and reporting adjusted risk estimates. Eight studies met the inclusion criteria, encompassing prospective cohorts, cross-sectional analyses, and systematic reviews. A narrative synthesis approach was adopted due to the heterogeneity of study designs and outcome measures. While findings across studies varied, several demonstrated statistically significant associations between long-term PPI use and increased risks of adverse outcomes, particularly in elderly or comorbid populations. However, many studies were limited by confounding, bias, and the inability to establish causality. The evidence underscores the need for cautious and judicious prescribing of PPIs, with periodic reassessment of the indication and consideration of deprescribing in low-risk patients. Further high-quality prospective studies and randomized trials are warranted to clarify these associations and guide clinical decision-making.