The side effect is rare, and the study doesn’t prove the drugs cause kidney failure. But earlier studies have also linked the pills to this side effect, and the association is worrisome because tens of millions of people a year take these pills, sold by prescription and over-the-counter in some countries, with brand names including Prilosec, Prevacid and Zegerid.
“There appears to be mounting observational evidence that PPIs – historically a class thought to be extremely safe – have some adverse effects,” said lead author Dr. Morgan Grams of Johns Hopkins University in Baltimore.
“Given the widespread use of PPIs, even relatively rare adverse effects can impact large numbers of people,” Grams added by email. “Thus, I think it wise to be judicious in the use of PPIs.”
PPIs stop cells in the stomach lining from producing too much acid. In that way, they help prevent ulcers and reduce reflux symptoms such as heartburn. While scientists aren’t certain how the drugs affect the kidneys, prior research has tied PPIs to a form of kidney inflammation known as interstitial nephritis.
For the study, Grams and colleagues analyzed two large sets of data to examine the connection between PPI use and kidney disease in the general population.
The analysis linked PPI use to an increased risk of chronic kidney disease in both data sets, although PPI users were also more likely than non-users to be overweight or on medication to lower blood pressure or cholesterol. High blood pressure can also increase the risk for kidney disease.
First, the researchers reviewed data on 10,482 people who were part of a study on atherosclerosis, or hardening of the arteries, tracking half of them for more than 14 years.
They found 56 incidents of chronic kidney disease among 322 people taking PPIs, compared with 1,382 incidents among 10,160 individuals who didn’t use the pills. In other words, if 1,000 PPI users were tracked for one year, researchers would see 14.2 new cases of chronic kidney disease, compared to a rate of 10.7 new cases if 1,000 non-PPI-users were followed for a year.
Researchers estimated that over 10 years, the absolute risk of chronic kidney disease was 11.8 percent among PPI users, versus 8.5 percent among nonusers.
In a second analysis, researchers examined data on 248,751 patients in the Geisinger Health System in Pennsylvania, with half of participants followed for at least six years.
This time, there were 1,921 incidents of chronic kidney disease among 16,900 PPI users, compared with 28,226 incidents among 231,851 non-users. The incident rate for PPIs was 20.1 per 1,000 person-years, compared with 18.3 per 1,000 person-years without the medication.
Researchers estimated that over 10 years, the absolute risk of chronic kidney disease among the Geisinger patients was 15.6 percent among PPI users, but just 13.9 percent if they didn’t take the pills.
It’s possible that the PPI users had other risk factors for kidney disease that were unrelated to the medications, the authors acknowledge in JAMA Internal Medicine.
Even so, the findings add to growing evidence suggesting that some patients may experience dangerous side effects from PPIs, Dr. Adam Schoenfeld and Dr. Deborah Grady of the University of California, San Francisco, note in an editorial.
Earlier research has linked the pills to kidney damage, heart problems, infections and fractures, they wrote.
“Doctors must weigh the risks and benefits before recommending PPIs and this study adds chronic kidney disease to the risk of rare, but serious side effects associated with PPI use,” Schoenfeld said by email.
Many patients with heartburn and indigestion don’t need PPIs, Schoenfeld added, noting that behavior and lifestyle changes such as getting more exercise and drinking less alcohol may have the same effect as PPIs for mild stomach symptoms.