Proton Pump Inhibitors Might Cause Chronic Kidney Disease

Public Citizen’s Health Research Group has long warned about the serious risks of the commonly used group of heartburn drugs known as proton pump inhibitors (PPIs; examples include omeprazole [PRILOSEC] and lansoprazole [PREVACID]).[1] Now, two recent studies have identified chronic kidney disease as another potential side effect.

The studies

The first study was published in February in the Journal of the American Medical Association (JAMA) Internal Medicine.[2] Researchers analyzed two sets of observational data to see whether the results were consistent across two different patient populations. One data set involved more than 10,000 patients followed for a median of about 14 years, while the other included nearly 250,000 patients followed for a median of six years.

No patients had evidence of chronic kidney disease at the beginning of the study. Patients using PPIs had up to a 50 percent increased risk of chronic kidney disease compared with non-users and up to a 39 percent increased risk compared with users of another commonly used class of heartburn drugs known as histamine-2-receptor antagonists (H2As; examples include famotidine [PEPCID] and ranitidine [ZANTAC]).

The authors speculated that PPIs might increase the risk of chronic kidney disease by repeatedly causing acute (sudden-onset) kidney injury. Indeed, PPIs have been linked in previous studies with a type of acute kidney injury known as acute interstitial nephritis.[3] The JAMA Internal Medicine study also found that PPIs significantly increased the risk of acute kidney injury, by up to 64 percent compared with non-users and by up to 58 percent compared with those on H2As.

The dose of the PPI also mattered: Twice-daily PPI use was associated with an even higher risk for both chronic kidney disease and acute kidney injury than once-daily use in this study. Unlike PPIs, H2As were not associated with an increased risk of either chronic or acute kidney disease.

The second study, published in April in the Journal of the American Society of Nephrology, found a 28 percent increased risk of chronic kidney disease, and a 96 percent increased risk of end-stage kidney disease (kidney disease requiring dialysis or a kidney transplant), in over 173,000 new PPI users when compared with over 20,000 new patients on H2As.[4] The risk of kidney harms grew the longer PPIs were used.

Despite being non-randomized in nature, both of these studies were particularly well-done for several reasons. The fact that the results of the earlier February study were consistent across two different patient populations makes it more likely that the observed increased risk is real. The authors of that study also accounted for multiple differences in patients, which minimizes the chance that some factor other than PPI use may have been responsible for the increased risk of chronic kidney disease and acute kidney injury.

Both studies compared PPIs with H2As, a class of drugs usually prescribed for the same conditions, in order to minimize the chance that something associated with the underlying disease being treated with the PPIs (as opposed to the PPIs) was responsible for the kidney outcomes.

Finally, the findings that the association with kidney harm increases with higher doses and longer durations of PPI use heightens the concern about the drugs’ link to kidney disease.

Other risks of PPIs

An editorial accompanying the February study described some other serious risks of PPIs that have been documented in a number of studies.[5] These include a severe type of diarrhea caused by the Clostridium difficile bacteria, low blood magnesium levels (which can lead to life-threatening heart rhythm disorders), hip and spine fractures in osteoporotic patients, and, possibly, pneumonia.

The authors of the editorial concluded, “Given the evidence that PPI use is linked with a number of adverse outcomes, we recommend that patients and clinicians discuss the potential benefits and risks of PPI treatment, as well as potential alternative regimens such as H2As or lifestyle changes, before PPIs are prescribed.”[6]

What You Can Do

All prescription PPIs, except dexlansoprazole (DEXILANT, KAPIDEX) and pantoprazole (PROTONIX), are effective, approved treatments for a gastrointestinal ulcer.

If you have heartburn, there are many nondrug approaches you can adopt to try to relieve your symptoms. Avoiding excessive amounts of alcohol, coffee, chocolate or foods high in fat, and, for nighttime heartburn, avoiding eating too close to bedtime and raising the head of the bed at night, can go a long way toward relieving heartburn symptoms.

If your symptoms persist, you can try drugs that are also effective but safer than PPIs. Over-the-counter antacids are the oldest and safest treatments for heartburn and have few side effects (except for in those with kidney disease, who should avoid antacids until consulting their doctors). If these do not work, then H2As should be tried before resorting to PPIs, as they are less potent suppressors of stomach acid and cause fewer serious side effects.

If you do eventually require a PPI, you should first discuss the risks of treatment with your doctor. Having such a discussion with one’s doctor is especially important given that PPIs are heavily overused, often for conditions for which they have not been approved as effective treatments.[7] To see a complete discussion of risks other than chronic kidney disease, see our in-depth article on PPIs in the November 2011 issue of Worst Pills, Best Pills News, also available at WorstPills.org.[8]

Proton Pump Inhibitors Approved in the U.S. (combination drugs excluded)

*We classify all prescription PPIs as Limited Use for heartburn. All prescription PPIs, except dexlansoprazole and pantoprazole, are approved for, and effective in treating, gastrointestinal ulcers.
**Over-the-counter PPIs are approved only for the short-term (14 days maximum) treatment of heartburn. We recommend that you use over-the-counter PPIs only after seeing a doctor for your heartburn symptoms.

References

[1] Proton pump inhibitors: Dangerous and habit-forming heartburn drugs. Worst Pills, Best Pills News. November 2011. /newsletters/view/772. Accessed April 13, 2016.

[2] Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176(2):238-246.

[3] Antoniou T, Macdonald EM, Hollands S, et al. Proton pump inhibitors and the risk of acute kidney injury in older patients: A population-based cohort study. CMAJ Open. 2015;3(2):E166-E171.

[4] Xie Y, Bowe B, Li T, et al. Proton pump inhibitors and risk of incident CKD and progression to ESRD. J Am Soc Nephrol. April 14, 2016. doi: 10.1681/ASN.2015121377.

[5] Schoenfeld AJ, Grady D. Adverse effects associated with proton pump inhibitors. JAMA Intern Med. 2016;176(2):172-174.
[6] Ibid.

[7] Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: What the clinician needs to know. Therap Adv Gastroenterol. 2012;5(4):219-232.

[8] Proton pump inhibitors: Dangerous and habit-forming heartburn drugs. Worst Pills, Best Pills News. November 2011. /newsletters/view/772. Accessed April 13, 2016.