Proton Pump Inhibitors

What are proton pump inhibitors (PPIs)?

Proton pump inhibitors, or PPIs, were introduced in the late 1980s and are used to treat acid-related disorders of the upper gastrointestinal tract, including peptic ulcers, gastroesophageal reflux disease (GERD), Zollinger-Ellison syndrome, and for the prevention of gastrointestinal adverse events caused by non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin. They are also used in combination with antibiotics for eradicating Helicobacter pylori, a bacterium that together with acid causes ulcers of the stomach and duodenum.

PPIs work to prevent ulcers and assist in the healing of ulcers in the esophagus, stomach, or duodenum by reducing the production of acid in the stomach wall.

These drugs are available both over-the-counter and by prescription and are among the most commonly used classes of medications in the United States. According to the National Health and Nutrition Examination Survey, the use of PPIs has increased from 3.4 percent to 7.0 percent among men and from 4.8 percent to 8.5 percent among women from 1999-2000 to 2011-2013. The survey also found that 14.9 million people received 157 million prescriptions for PPIs in 2012.

Proton Pump Inhibitors and Kidney Disease

In 2017, a study published in the journal Kidney International found that people who used proton pump inhibitors were more likely to develop chronic kidney disease (CKD) even if they haven’t suffered acute kidney injury (AKI) previously. According to the study, PPI users had a 26% increased risk of CKD than users of another common class of acid-reducing medications known as H2 blockers.

Another study published in JAMA Internal Medicine found that PPI users were also more likely to suffer from CKD than people who did not use PPIs. Researchers also noted that many PPI users were taking the drugs 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.

In a study published in BMC Nephrology in August 2016, researchers concluded that proton pump inhibitors were associated with an increased risk of chronic kidney disease and death. Chronic kidney disease can result when acute interstitial nephritis (AIN) goes undiagnosed.

Proton Pump Inhibitors and Death

A new study published in the British medical journal The BMJ investigating the death rates among PPI users found that people who used the drug were at an increased risk of dying from cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. The study, led by Ziyad Al-Aly, M.D., with Washington State University School of Medicine in St. Louis, focused on 157,000 veterans who were prescribed PPIs for the first time and followed them for 10 years. The longer the PPI use, the greater the risk of death, Al-Aly found. Likewise, a patient’s history of these conditions did not influence the results of the study.

Proton Pump Inhibitors and COVID-19

A study published August 2020 in the American Journal of Gastroenterology found that people who used PPIs were at increased risk of contracting COVID-19. Specifically, individuals who took PPIs twice daily were more likely to test positive for the virus than those using lower doses once a day. Likewise, people who used a class of heartburn drugs known as histamine-2 receptor antagonists, or H2 blockers, were not at increased risk of contracting COVID-19.