Proton pump inhibitors (PPIs), which are commonly used to reduce acid in the stomach, appear to be associated with an increased risk of chronic kidney disease (CKD), but more research is needed to determine whether PPI use causes kidney damage, according to an article published online in JAMA Internal Medicine.
PPIs are among the most commonly prescribed medications in the U.S., and an estimated 25% to 70% of prescriptions for these drugs may have no appropriate indication for use. Other observational studies have linked PPIs to serious adverse health outcomes. However, the authors note that no population-based studies have looked at the association between PPI use and the risk of CKD.
Morgan E. Grams, MD, PhD, of Johns Hopkins University, Baltimore, and his coauthors quantified the association between PPI use and incident CKD in the general population using data on self-reported PPI use in the Atherosclerosis Risk in Communities (ARIC) study, in which 10,482 participants were followed for a median period of nearly 14 years. The authors also used an outpatient PPI prescription database at the Geisinger Health System in Pennsylvania, which followed 248,751 people for a median period of six years.
At baseline, PPI users in both databases were more likely to have a higher body mass index and to be taking antihypertensive, aspirin, or statin medications.
In the ARIC group, 56 incident CKD events occurred among 322 baseline PPI users (14.2 per 1,000-person years), and 1,382 events occurred among 10,160 baseline nonusers (10.7 per 1,000 person-years). PPI use was associated with a risk of incident CKD in both unadjusted and adjusted analyses. The 10-year estimated absolute risk of CKD among the 322 baseline PPI users was 11.8%, whereas the expected risk had they not used PPIs was 8.5%, according to the results.
In the replication group at Geisinger, 1,921 incident CKD events occurred among 16,900 baseline PPI users (20.1 per 1,000 person-years), and 28,226 events occurred among 231,851 baseline nonusers (18.3 per 1,000 person-years). The 10-year absolute risk of CKD among the 16,900 baseline PPI users was 15.6%, and the expected risk had they not used PPIs was 13.9%.
The authors note several study limitations, including the fact that participants who were prescribed PPIs may have been at increased risk of CKD for reasons unrelated to their PPI use.
“We note that our study is observational and does not provide evidence of causality. However, a causal relationship between PPI use and CKD could have a considerable public health effect given the widespread extent of use. More than 15 million Americans used prescription PPIs in 2013, costing more than $10 billion. Study findings suggest that up to 70% of these prescriptions are without indication and that 25% of long-term PPI users could discontinue therapy without developing symptoms. Indeed, there are already calls for the reduction of unnecessary use of PPIs,” the authors conclude.
Adam Jacob Schoenfeld, MD, and Deborah Grady, MD, MPH, of the University of California, San Francisco, wrote a related editorial summarizing recent data on the adverse effects of PPI use.
“A large number of patients are taking PPIs for no clear reason –– often remote symptoms of dyspepsia or ‘heartburn’ that have since resolved. In these patients, PPIs should be stopped to determine if symptomatic treatment is needed,” they remarked.