Proton Pump Inhibitor Use Linked to High Risk for Incident Chronic Kidney Disease

Proton pump inhibitors (PPIs) have been widely prescribed in the United States for several decades, and are some of the most commonly used drugs worldwide.^1,2

This is largely a result of their common use in patients with dyspepsia and those who are receiving antiplatelet therapy and require prevention of gastrointestinal bleeding, as well as the belief that PPIs have few adverse effects. However, growing evidence has shown that PPIs are often overprescribed, and that they may have several adverse effects. Benjamin Lazarus, MBBS, Department of Epidemiology, Johns Hopkins University, Baltimore, MD, and colleagues conducted a population-based cohort study and found that patients who use PPIs are at higher risk for incident chronic kidney disease (CKD).

As part of their research, the authors evaluated self-reported use of PPIs among patients who participated in the Atherosclerosis Risk in Communities study (N = 10,482; estimated glomerular filtration rate of ≥60 mL/min/1.73 m²), and outpatient’s PPI prescription from the Geisinger Health System (N = 248,751; estimated glomerular filtration rate of ≥60 mL/min/1.73 m²). The use of a histamine₂ receptor antagonist was considered a negative control and an active comparator.

The mean age of patients in the Atherosclerosis Risk in Communities study was 63.0 years; 43.9% were men. Patients who received PPIs were more often white, obese, and taking antihypertensive medication compared with those who did not receive PPIs. In addition, PPI use was associated with incident CKD (hazard ratio [HR], 1-45); after adjusting for demographic, socioeconomic, and clinical variables, HR was 1.50; and in an analysis evaluating PPI use as a time-varying variable, adjusted HR was 1.35. PPI association with incident CKD continued to be observed when patients receiving PPIs at baseline were compared directly with patients receiving histamine₂ receptor antagonists (adjusted HR, 1.39), and with propensity score–matched nonusers (HR, 1.76). In the Geisinger Health System replication cohort, use of PPIs was associated with CKD in all analyses, including a time-varying, new-user design (adjusted HR, 1.24). Furthermore, PPI dosing twice daily (adjusted HR, 1.46) was associated with a higher risk for CKD than once-daily dosing (adjusted HR, 1.15).

“PPI use is associated with a higher risk of incident CKD,” Mr Lazarus and colleagues concluded. “Future research should evaluate whether limiting PPI use reduces the incidence of CKD.”

References

1. Schoenfeld AJ, Grady D. Adverse effects associated with proton pump inhibitors. JAMA Intern Med. 2016:1-3.
2. Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016:238-246.