Proton pump inhibitors and acute kidney injury: a nested case-control study

Proton pump inhibitors (PPI) are a widely-used class of drugs for the treatment of gastro-esophageal reflux disease and other acid-related disorders of the gastrointestinal tract. As a class, PPIs have demonstrated a favorable safety profile. However, case reports have suggested that this class of drugs may be linked to acute kidney injury, which may in turn lead to chronic injury or failure. The objective of this study was to determine if an association between PPIs and kidney failure exists and to estimate an effect size for the relationship between PPI use and renal disease.

A nested case-control study was conducted in a privately insured population in a single Midwestern state including a total of 184,480 patients aged 18 years or older who were continuously enrolled with the insurer for at least 24 months between September 2002 and November 2005.

Renal disease was positively associated with PPI use (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.27, 2.32, p < 0.001) even after controlling for potential confounding conditions. After removing patients with potential confounding disease states from the study population, the number of cases (195 of the 854) and controls (607) was lower, but the relationship between renal disease and PPI use remained consistent (OR 2.25, CI 1.09-4.62, p < 0.001).

Patients with a renal disease diagnosis were twice as likely to have used a previous prescription for a PPI. Therefore, it is necessary for physicians to increase recognition of patient complaints or clinical manifestations of this potentially harmful event in order to prevent further injury.