January 11, 2016
3 min read

PPI use linked to increased risk for chronic kidney disease

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Using proton pump inhibitors was found to be associated with a higher risk for incident chronic kidney disease, according to study results published in JAMA Internal Medicine.

While PPIs have been linked to acute interstitial nephritis, “to our knowledge, no population-based studies have evaluated the association between PPI use and the risk of [chronic kidney disease],” the researchers wrote. “The objective of this study was to quantify the association between PPI use and incident kidney disease in the general population.”

From May to October 2015, researchers evaluated data on 10,482 patients (mean age, 63 ± 5.6 years; 43.9% men) enrolled in the Atherosclerosis Risk in Communities (ARIC) study who were followed from a baseline visit between February 1996 and the end of January 1999, through December 2011 (median follow-up, 13.9 years). All included patients had a minimum estimated glomerular filtration rate of 60 mL/min/1.73 m2. Findings were then replicated in an administrative cohort of 248,751 patients with the same minimum glomerular filtration rate who received care at the Geisinger Health System between February 1997 and October 2014 (median follow-up, 6.2 years).

Overall, 56 incident chronic kidney disease events occurred among the 322 patients in the ARIC cohort who used PPIs at baseline (14.2 per 1,000 person-years) and 1,382 events occurred among the 10,160 patients who did not use PPIs at baseline (10.7 per 1,000 person-years). In the replication cohort, 1,921 events occurred among 16,900 patients who used PPIs at baseline (20.1 per 1,000 person years) and 29,226 events occurred among 231,851 patients who did not use PPIs at baseline (18.3 per 1,000 person-years).

Unadjusted analysis of the ARIC cohort revealed an association between PPI use and incident chronic kidney disease (HR = 1.45; 95% CI, 1.11-1.9), which persisted after adjusting for potential confounders (HR = 1.5; 95% CI, 1.14-1.96), and when PPI use was modeled as a time-varying ever-use variable (HR = 1.35; 95% CI, 1.17-1.55).

“The 10-year estimated absolute risk of [chronic kidney disease] among the 322 baseline PPI users was 11.8%, while the expected risk had they not used PPIs was 8.5% (absolute risk difference, 3.3%),” the researchers wrote.

All analyses of the Geisinger Health System replication cohort also demonstrated an association between PPI use and chronic kidney disease, and a higher risk was associated with twice-daily PPI dosing (aHR = 1.46; 95% CI, 1.28-1.67) compared with once-daily dosing (aHR = 1.15; 95% CI, 1.09-1.21).

“The 10-year absolute risk of [chronic kidney disease] among the 16,900 baseline PPI users was 15.6%, and the expected risk had they not used PPIs was 13.9% (absolute risk difference, 1.7%),” the researchers wrote.

Sensitivity analyses showed PPI users also had an increased risk for chronic kidney disease compared with H2 receptor antagonist users in the ARIC cohort (adjusted HR = 1.39; 95% CI, 1.01-1.91) and in the replication cohort (aHR = 1.29; 95% CI, 1.19-1.4). The association was also demonstrated in baseline PPI users compared with propensity score-matched nonusers in the ARIC cohort (HR = 1.76; 95% CI, 1.13-2.74) and the replication cohort (HR = 1.16; 95% CI, 1.09-1.24), and also in a time-varying new-user design in the replication cohort (aHR = 1.24; 95% CI, 1.2-1.28).

Comparable associations between PPIs and acute kidney injury were also observed in both cohorts.

“In summary, we found that PPI use is an independent risk factor for [chronic kidney disease] and [acute kidney injury], but H2 antagonist use is not,” the researchers concluded.

“Although this is a large, high-quality observational study, additional confirmation would be helpful, especially since chronic kidney disease is a common condition,” Adam Jacob Schoenfeld, MD, and Deborah Grady, MD, MPH, from the University of California, San Francisco, wrote in a related editorial. “Given the evidence that PPI use is linked with a number of adverse outcomes, we recommend that patients and clinicians discuss the potential benefits and risks of PPI treatment, as well as potential alternative regimens such as histamine H2 receptor antagonists or lifestyle changes, before PPIs are prescribed. – by Adam Leitenberger

Disclosures: Grams reports she is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Schoenfeld and Grady report no relevant financial disclosures.