Patients taking a popular type of heartburn drug may be at an increased risk for kidney damage, a new series of studies suggests. Researchers at the world’s most prestigious universities have linked proton pump inhibitors, some of the world’s most commonly-prescribed drugs, to conditions ranging from acute kidney injury to renal failure.
Scientists Find Evidence Of Kidney Risk
While the FDA has not yet made an announcement on the subject, mounting medical evidence suggests that Nexium, Prilosec, Prevacid and other proton pump inhibitors (PPIs) may impair kidney function to a devastating degree.
But this new data shouldn’t come as much of a surprise. In reality, the medical community has suspected a link between PPI use and kidney damage for at least 24 years.
Acute Interstitial Nephritis
Researchers have long suspected that PPIs can cause a kidney condition called “acute interstitial nephritis,” or AIN. Acute interstitial nephritis is usually an adverse reaction to a drug, much like an allergic reaction. In 1992, doctors described the case of one patient who, after being prescribed a proton pump inhibitor, had suffered from an inflamed kidney – a textbook case of AIN. By 2004, the evidence for a link was insurmountable. That year, a group of Australian researchers at the American Society of Nephrology said:
“with the ever more widespread use of this class of medications, PPI-induced AIN is likely to become more frequent. There is now evidence to incriminate all the commercially available PPIs, suggesting there is a class effect.”
That’s right. It doesn’t matter which proton pump inhibitor you take. The risk of developing acute interstitial nephritis exists with all of them. Here’s a full list of currently-available proton pump inhibitors, both active ingredients and brand names when applicable:
- Dexilant (active ingredient: dexlansoprazole)
- Nexium (active ingredient: esomeprazole)
- Prevacid (active ingredient: lansoprazole)
- Generic lansoprazole
- Prilosec (active ingredient: omeprazole)
- Generic omeprazole
- Protonix (active ingredient: pantoprazole)
- Generic pantoprazole
- AcipHex (active ingredient: rabeprazole)
As we just noted, the risk of kidney injury appears to be equally distributed among all of these popular medications.
Acute Kidney Injuries
Perhaps even more troubling, researchers have noted another possibility: acute interstitial nephritis often progresses to acute renal failure (ARF). In other words, proton pump inhibitors are certainly causing AIN, a condition that itself can be life-threatening, but often turns into full-blown kidney failure.
To arrive at their conclusion, now widely accepted within the medical community, the Australian researchers looked at health records from just two hospitals in Australia, searching for examples of kidney impairment that had been linked to proton pump inhibitors. Their review discovered:
- 18 cases of “biopsy-proven PPI-induced AIN causing ARF”
- 31 cases of “biopsy-proven interstitial nephritis”
- 10 cases of “suspected interstitial nephritis”
- 20 cases of “unclassified acute renal failure”
- 26 cases of “renal impairment”
Moreover, all of the 5 then-available proton pump inhibitors had been implicated in at least one of these cases. In their conclusion, the scientists advised caution: “increased awareness might facilitate more rapid diagnosis and management of this potentially reversible condition.”
Atypical Symptoms Make Diagnosis Hard
Vigilance is certainly important here. Acute interstitial nephritis is often signaled by a triad of symptoms: fever, rash and joint pain. But as Donald Klepser, a professor of pharmacy at the University of Nebraska, wrote in 2013, “in case reports of PPI-induced AIN, the triad of symptoms was present in a minority of subjects.” Instead, these patients present with a roster of “nonspecific” symptoms, things like fatigue, weight loss and nausea that could be caused by numerous other conditions. Thus, from the start, it’s difficult for doctors to confirm a diagnosis of acute interstitial nephritis caused by proton pump inhibitors.
That necessary diagnosis becomes even more difficult when physicians are ill-informed. But pharmaceutical manufacturers have never been particularly prompt in warning patients or the health community. In fact, the companies behind proton pump inhibitors were remarkably slow to mention acute interstitial nephritis in their product labeling. So slow that the FDA was forced to step in, mandating a warning for AIN in October 2014. Even with this new warning in place, doctors in Toronto were still calling acute kidney injuries an “underappreciated” side effect of PPIs in 2015.
Chronic Kidney Disease
Later research has only strengthened the association, while further investigating the conditions that acute kidney injuries can cause.
In one of the most recent studies, researchers at Johns Hopkins University and Yale looked into the association between proton pump inhibitors and chronic kidney disease, a progressive impairment of kidney function and potential consequence of acute interstitial nephritis.
Out of 10,482 patients, people taking PPIs were around 45% more likely to suffer chronic kidney disease (CKD). After controlling for other factors that predict for chronic kidney disease, the risk increased, to around 50%. To provide more forceful results, the researchers performed an identical analysis using another data set. Again, proton pump inhibitors were associated with an increased risk for chronic kidney disease. For patients who had just been placed on PPIs, the risk appeared to increase by 24%. Dosage also seemed to play a role. While patients who took only one dose per day were at a 15% increased risk of developing CKD, patients taking two doses per day were observed at a 46% increased risk.
Strong Early Evidence Confirmed
The study was published in the Journal of the American Medical Association (JAMA) in February 2016. Later that month, a second group of researchers provided the medical community with strikingly similar results. Their intent was somewhat different, however. Rather than comparing PPI patients to members of the general population, the researchers used data from St. Louis’ Veterans Affairs Health Care System to contrast proton pump inhibitors and H2 receptor antagonists, another drug class used to treat stomach acid disorders.
Like the JAMA article, this second study found an elevated risk among patients taking proton pump inhibitors. Where chronic kidney disease was concerned, PPI users were 28% more likely to suffer the condition than their peers. But the risk of end-stage renal disease, or kidney failure, was even higher. Patients on PPIs were 96% more likely to suffer kidney failure than patients taking H2 receptor antagonists.
Length Of Treatment Matters
Perhaps most importantly, this newest study suggests that the risk of kidney disease increases with time. The patients involved (numbering 10,482) had been followed over the course of 10 years.
Short courses of treatment are crucial when it comes to proton pump inhibitors. The drugs have a relatively positive risk-to-benefit profile when prescribed for brief periods of time. In fact, many researchers consider PPIs the most effective, and safest, option for patients suffering from gastroesophegeal reflux disease, stomach ulcers and other conditions in which gastric acid is a problem. But now that PPIs have become commonplace, and with at least 11 generic formulations on the market, doctors have begun prescribing proton pump inhibitors for longer courses of treatment.
This is a problem. We just don’t know how long-term proton pump inhibitor use will alter the human body. Now, we’re receiving early warnings that kidney disease may be one of the risks.
The Continuum Of Kidney Disease
Researchers now believe that proton pump inhibitors may be responsible for triggering a cascade of ever-more-serious kidney conditions. Like dominoes, the acute interstitial nephritis caused by PPIs can itself lead to long-term kidney impairment, and eventually, chronic kidney disease and renal failure.
Noting this progression, researchers led by Donald Klepser reviewed the insurance records of 184,480 patients covered continuously between September 2002 and November 2005. Of those patients, 854 people who had made at least two claims involving a diagnosis of acute renal disease – the first domino to fall – were identified. After matching these patients to healthier peers, the researchers found that people who had been diagnosed with renal diseases were 72% more likely to have been prescribed proton pump inhibitors. After controlling for other factors that may predispose patients to developing kidney disease, the association grew even stronger. With these “confounding” factors eliminated, PPI users were 2.25 times more likely to suffer renal disease.
The study was published by BioMed Central Nephrology on July 16, 2013.
Have Any Lawsuits Been Filed Yet?
On May 3, 2016, a man from Illinois filed suit against AstraZeneca, the manufacturer of blockbuster PPI Nexium, claiming the “Purple Pill” caused his kidney failure.
The man says AstraZeneca ignored years of medical research, choosing to push its heartburn drug toward greater profits rather than warn patients of its risks. In his words, “despite clear knowledge that Nexium causes a significantly increased risk of CKD and acute kidney injuries,
The case, filed in the US District Court for the Southern District of Illinois, is now progressing through pre-trial proceedings. It was logged as case number 3:16-cv-00493-SMY-DGW.