Millions of americans take prescription drugs called PPIs, or proton pump inhibitors, to treat heartburn, ulcers and other gastrointestinal problems. And many of these PPIs are widely available as over-the-counter drugs under brand names that include Prevacid, Prilosec, Nexium and Protonix. While ppis are effective at reducing stomach acid, they have also been linked to health problems, including low magnesium levels, bone fractures and the gut infection C. Difficile.

A trio of studies conducted by researchers at Washington University School of Medicine indicates that longtime use of PPIs is associated with serious kidney damage, including kidney failure, as well as an increased risk of death.

“We advise people to limit the use of PPIs only to when they are medically necessary and for the shortest duration possible with the smallest effective dose,” says Ziyad Al-Aly, MD, a Washington University kidney specialist and senior author of the studies.

The research involved analyzing medical records in national Veteran’s Administration databases to identify more than 173,000 users of PPIs and, as a comparison, 20,000 users of other stomach-acid suppressing drugs called H2 blockers.

Following the study’s participants for five years, Al-Aly and a team of 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 age and other health conditions associated with PPI use, the team found a 28 percent increased risk of kidney damage among PPI users.

PPI users were also 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 people studied.

Among more than half of PPI users who developed chronic kidney damage, a follow-up study indicated that such problems developed silently, without symptoms, gradually eroding kidney function and leading to long-term kidney damage or, in some cases, kidney failure.

In a third study, PPI users had a 25 percent increased risk of dying over the next five years, compared with those taking H2 blockers. The database did not include information on cause of death. However, the researchers calculated that, for every 500 people taking PPIs for a year, there is one extra death that would not have otherwise occurred. Given the millions of people who take PPIs regularly, this could translate into thousands of excess deaths every year, Al-Aly says.

Although the recommended treatment regimen for most PPIs is short — two to eight weeks for ulcers, for example — many people end up taking the drugs for months or years.

“A lot of times people get prescribed PPIs for a good medical reason, and patients just keep getting refill after refill,” Al-Aly says. “Physicians and patients should regularly reassess the use of such medications, and physicians should stop prescribing the medications if they’re not necessary. Most of the time, people don’t need to take PPIs for years.”

Originally published by Washington University School of Medicine at medicine.wustl.edu/news