Inappropriate PPI use linked with CKD risk

70% of prescriptions are unnecessary; 25% of long-term PPI users may be discontinued

Editors: Dr. Reuben C. Ricallo . Dr. Ereka C. Ricafranca

PROTON PUMP inhibitors (PPIs) are almost routinely given every time there is clinical suspicion of an acid peptic disease, or as a prophylactic measure to prevent upper gastro-intestinal (GI) bleeding when the patients are given drugs that can potentially cause gastritis.

Physicians are warned that PPIs may be associated with increased risk for chronic kidney disease (CKD), based on two population-based analyses published online January 11, 2016 in JAMA Internal Medicine.

Although known CKD risk factors, such as diabetes mellitus and hypertension, are also increasing in prevalence, the authors wrote that it’s possible, too, that PPIs might be partly to blame for the rapid increase in CKD prevalence more than what one would expect based on its traditional risk factors.

Benjamin Lazarus, MBBS, from the Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, and the Department of Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Australia, and his colleagues wrote: “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.”

He added that in 2013, more than 15 million Americans used prescription PPIs, costing more than $10 billion. “Study findings suggest that up to 70 percent of these prescriptions are without indication and that 25 percent of long-term PPI users could discontinue therapy without developing symptoms. Indeed, there are already calls for the reduction of unnecessary use of PPIs,” Lazarus added.

In the study, rates of incident CKD between patients taking PPIs and those not taking PPIs were compared among 10,482 subjects in the Atherosclerosis Risk in Communities (ARIC) study. Patients were followed up for a median of 13.9 years. At baseline, 322 (3.1 percent) of the ARIC participants were taking PPIs.

The same approach was also done using data from 248,751 subjects in the Geisinger Health System in Pennsylvania, who were followed up for a median of 6.2 years; and wherein, at baseline, 16,900 (6.8 percent) of the Geisinger patients had prescriptions for outpatient PPIs.

Excluded in both studies were individuals with baseline estimated glomerular filtration rates of below 60 mL/min per 1.73 m2. Hazard ratios were adjusted for demographic, socioeconomic, and clinical variables.

Looking at omeprazole, the first PPI in the United States, which was launched in 1988, the authors wrote that PPI use increased dramatically in both cohorts. For example in the ARIC cohort, from 1996 through 1999 and final follow-up in 2011, PPI use dramatically increased from 3.1 percent to more than 25 percent.

Noting the increase in PPI use over time, the researchers modeled PPI as a time-varying ever-use variable, and this process also showed a significant increase in CKD risk associated with ever using PPIs (HR, 1.35; 1.17 – 1.55; P < .001) compared with no PPI use.

“The 10-year estimated absolute risk of CKD among the 322 baseline PPI users was 11.8 percent while the expected risk had they not used PPIs was 8.5 percent (absolute risk difference, 3.3 percent),” the authors reported.

The researchers further reported that in the Geisinger Health System cohort, there were 1,921 incident CKD cases among 16,900 baseline PPI users (20.1 per 1000 person-years) compared with 28,226 incident cases among 231,851 baseline nonusers (18.3 per 1000 person-years. After adjusting for potential confounders, the CDK HR was 1.17 (CI, 1.12 – 1.23; P < .001). In the time-varying ever-use model, the adjusted HR was 1.22 (P < .001).

Based on the analysis, the risk appears to be linked with PPI use itself and not other agents as histamine¬2 receptor antagonists, which are also used to treat gastroesophageal reflux.

Other editorialists commenting on the study in the same JAMA issue—Jacob Schoenfeld, MD, from the University of California, San Francisco, and Deborah Grady, MD, MPH, from the University of California, San Francisco, and VA Medical Center, San Francisco—recommended that clinicians prescribe alternatives to PPI such as histamine H2 receptor antagonists or lifestyle changes before prescribing PPIs. “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 wrote. With Medscape and JAMA Internal Medicine reports

Vital Signs Issue 83 Vol. 4, January 1-31 2016