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Popular heartburn drugs may cause serious kidney damage

Research indicates proton pump inhibitors should be used only sparingly

by Kristina SauerweinMay 5, 2016

Robert Boston

Extended use of drugs to treat heartburn, ulcers and acid reflux may lead to serious kidney damage, including kidney failure, according to a study by researchers at Washington University School of Medicine in St. Louis and Veterans Affairs St. Louis Health Care System.

More than 15 million Americans have prescriptions for so-called proton pump inhibitors (PPIs), which decrease gastric acid production and generally have been considered safe.

Furthermore, researchers found the risk of kidney problems rises the longer patients take the medications, sold under the brand names Prevacid, Prilosec, Nexium and Protonix, among others.

The epidemiological study is available online in the Journal of the American Society of Nephrology.

“We advise patients to limit the use of PPIs only to when they are medically necessary and for the shortest duration possible,” said Ziyad Al-Aly, MD, an assistant professor of medicine at Washington University and the study’s senior author.

In collaboration with scientists at the Veterans Affairs’ Clinical Epidemiology Center, Washington University researchers examined national VA databases to identify 173,321 new users of PPIs and 20,270 new users of an alternative class of stomach-acid suppressing drugs called histamine H2 receptor blockers. Following the patients for five years, the researchers found that chronic kidney disease affected 15 percent of PPI users who took the drugs over the course of the study compared with 11 percent of H2 blockers. After controlling for factors such as age and other health conditions that PPIs were associated with, researchers found a 28 percent increased risk of kidney damage among PPI users.

PPI users also were at a significantly higher risk – 98 percent – of developing kidney failure compared with users of H2 blockers, although this occurred in less than 1 percent of the overall patients studied.

“The general assumption is that PPIs as a drug class are safe,” said Al-Aly, who also is the VA’s associate chief of staff for research and education and co-director of the Clinical Epidemiology Center. “PPIs do not receive the same level of scrutiny as many other drugs in terms of indication for initiating treatment and duration of therapy.”

Similar studies – including one published earlier this year by researchers at Johns Hopkins University in The Journal of the American Medical Association – reached similar conclusions about the elevated risks of PPIs. Other studies have linked PPIs to health problems such as fractured bones and infections.

“Nephrologists have been aware that PPIs can cause injury to the kidneys through an allergic reaction, but this has been felt to be exceedingly rare,” said Benjamin Humphreys, MD, PhD, an associate professor and director of the School of Medicine’s Division of Nephrology. “This important study suggests that kidney damage may be far more common than anyone suspected. The large number of patients analyzed provides significant power to bolster the team’s conclusions.”

The new research does not provide direct evidence that PPIs cause kidney damage. However, potential negative connections need to be taken seriously, especially since PPI use is so widespread, said Yan Xie, the study’s lead author and a biostatistician at the Clinical Epidemiology Center.

Xie added that the number of people taking PPIs is likely higher than 15 million because the figure does not include PPIs bought over-the-counter without prescriptions. The drugs are popular because they quickly relieve symptoms of heartburn and other conditions linked to increased stomach acid.

“The constellation of findings – the totality of evidence – is compelling,” Xie said. “The public and the medical community should be aware of the possible risk and should exercise judicious use of PPI and limit use to where it is medically necessary and to the shortest duration possible.”

The researchers called for further study about the safety of PPIs. “We are interested in leveraging the availability of big data, including VA data and other data sources, to advance our understanding of potential long-term adverse events of widely prescribed pharmaceuticals,” Xie said. “The goal is to transform data into knowledge that would promote better vigilance around pharmaceuticals as well as advance and protect public health.”

Washington University School of Medicine‘s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.