Proton pump inhibitors are associated with risk of chronic kidney disease, study findsBMJ 2016; 352 doi: https://doi.org/10.1136/bmj.i128 (Published 12 January 2016) Cite this as: BMJ 2016;352:i128
Proton pump inhibitor use is associated with a 20-50% higher risk of incident chronic kidney disease, an observational US study published in JAMA Internal Medicine has found. However, the authors said that further research was needed to determine whether the link is causal.1
Researchers followed up 10 482 participants in the Atherosclerosis Risk in Communities study for a median of 13.9 years and found that the risk of chronic kidney disease was 50% higher in self reported proton pump inhibitor users than in non-users.
They found 56 incident chronic kidney events among the 322 baseline users of proton pump inhibitors (14.2 per 1000 person years) and 1382 events among 10 160 non-users (10.7 per 1000 person years). After adjusting for potential confounders including socioeconomic status, comorbidities, and use of other medicines, the risk of kidney disease was 50% higher in patients who used proton pump inhibitors than in non-users (hazard ratio 1.50 (95% confidence interval 1.14 to 1.96); P=0.003).
The 10 year estimated absolute risk of chronic kidney disease among proton pump users was 11.8%, and the expected risk, had they not used them, was 8.5%, the study showed. Similar findings were demonstrated for the outcome of acute kidney injury.
The risk was specific to proton pump inhibitors because the use of H2 receptor antagonists, which are prescribed for the same indication, was not independently associated with chronic kidney disease.
The findings were then replicated in a second large cohort of 248 751 patients using proton pump inhibitors prescribed in the Geisinger Health System, who were followed for a median of six years. In this cohort the researchers found 1921 incident chronic kidney disease events among 16 900 users (20.1 per 1000 person years) and 28 226 events among 231 851 non-users (18.3 per 1000 years). Proton pump inhibitor use was significantly associated with chronic kidney disease (adjusted hazard ratio 1.24 (1.20 to 1.28)). The study also found that patients receiving proton pump inhibitors twice a day were at higher risk than those receiving them once a day.
The authors noted that participants in the study who had proton pump inhibitors prescribed may be at higher risk of chronic kidney disease for reasons unrelated to their use of the drugs.
“We note that our study is observational and does not provide evidence of causality,” they wrote. “However, a causal relationship between proton pump inhibitor use and chronic kidney disease could have a considerable public health effect given the widespread extent of use.
“More than 15 million Americans used prescription proton pump inhibitors in 2013, costing more than $10bn [£6.86bn; €9.18bn]. Study findings suggest that up to 70% of these prescriptions are without indication and that 25% of long term proton pump inhibitor users could discontinue therapy without developing symptoms.”
Cite this as: BMJ 2016;352:i128