Stomach acid drugs linked to chronic kidney disease

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Taking a class of drugs commonly used to reduce acid in the stomach is linked to a higher risk of developing chronic kidney disease, compared with not taking them.
Stomach and esophagus
Over 15 million Americans used prescription PPIs - drugs that reduce stomach acid - in 2013, at a cost of over $10 billion.

This was the finding of a new study led by the Johns Hopkins University in Baltimore, MD, and published in JAMA Internal Medicine.

However, the authors also point out that finding a link between use of proton pump inhibitors (PPIs) and chronic kidney disease does not prove the drugs actually cause the disease - that is for further studies to establish.

It could be, they suggest, that the participants who were prescribed PPIs may have been at higher risk of chronic kidney disease for reasons unrelated to their PPI use.

However, the researchers also note that previous studies have linked use of PPIs to a form of kidney inflammation called acute interstitial nephritis.

PPIs are among the most commonly used drugs worldwide. They are used to relieve symptoms of acid reflux and gastroesophageal reflux disease (GERD). They are also prescribed for treating peptic or stomach ulcers and damage to the lower esophagus caused by acid reflux.

PPIs work by reducing the amount of stomach acid made by cells in the lining of the stomach. They are not the same as antacids, which work by neutralizing excess acid after it has entered the stomach.

There are many types and brands of PPI; examples include omeprazole (brand name Prilosec, also available without a prescription), esomeprazole (Nexium) and lansoprazole (Prevacid). The side effects vary from drug to drug.

In an accompanying editorial article - where they summarize recent evidence on the adverse effects of taking PPIs - Drs. Adam Jacob Schoenfeld and Deborah Grad, of the University of California-San Francisco, note that:

"A large number of patients are taking PPIs for no clear reason - often remote symptoms of dyspepsia or 'heartburn' that have since resolved."
10-year risk of kidney disease higher for PPI users

For their study, the Johns Hopkins researchers and their colleagues first analyzed data on 10,482 participants followed up for a median of nearly 14 years in the Atherosclerosis Risk in Communities (ARIC) study.

Fast facts about acid reflux

    Acid reflux, or gastroesophageal reflux (GER), happens when stomach contents come back up into the esophagus
    It is felt as heartburn when stomach acid touches the lining of the esophagus
    A more serious, persistent form - gastroesophageal reflux disease (GERD) - affects about 20% of the US population.



They then replicated the results in a bigger cohort of 248,751 participants followed up for a median of 6 years - these participants were members of the Geisinger Health System in Pennsylvania.

They found that at the beginning of the monitoring period, PPI users in both groups were more likely to have a higher body mass index (BMI) and to be taking aspirin, statins or drugs to control high blood pressure.

In the ARIC group, 56 of 332 participants using PPIs developed chronic kidney disease, compared with 1,382 of 10,160 non-users. These figures translate to 14.2 and 10.7 per 1,000-person years, respectively. Participants were classed as a PPI user if they were taking the drugs at the start of the follow-up.

Further analysis of these ARIC figures revealed that the 10-year absolute risk of developing chronic kidney disease in the PPI users was 11.8%, compared with 8.5% if they had not used PPIs.

When they repeated this same analysis in the Geisinger cohort, the researchers found 1,921 of 16,900 PPI users and 28,226 of 231,851 of non-users developed chronic kidney disease, which translates to 20.1 and 18.3 per 1,000 person-years, respectively.

Again, further analysis of the larger cohort showed PPI use was associated with higher risk of disease. The 10-year absolute risk of developing chronic kidney disease among the PPI users was 15.6%, compared with 13.9% had they not used the drugs.

Commenting on their own findings, the authors emphasize the point that their study "is observational and does not provide evidence of causality," but should the link between PPI use and chronic kidney disease prove to be causal, then it could have important implications for public health, given the widespread use of the drugs.

Over 15 million Americans used prescription PPIs in 2013 at a cost of over $10 billion, they note, and conclude:

    "Study findings suggest that up to 70% of these prescriptions are without indication and that 25% of long-term PPI users could discontinue therapy without developing symptoms. Indeed, there are already calls for the reduction of unnecessary use of PPIs."

In 2010, Medical News Today reported how a study by researchers from Seoul National University Hospital in South Korea, published in the Canadian Medical Association Journal, also found that use of PPIs and another class of acid reflux drug called histamine2 receptor antagonists may be linked to higher risk of pneumonia.