Large study connects proton pump inhibitors with risks for CKD, AKI

Issue: May 2019

A study that examined the use of common heartburn medications in a large patient population showed ties between the medications and CKD — and acute kidney failure — later in life.

Perspective from Leanna Tyshler, MD

University at Buffalo researchers reviewed the medical records of 190,000 patients older than 15 years of age and found acid reflux drugs increased the risk of kidney disease by 20% and the risk of kidney failure by four times compared to individuals unexposed to the drugs. Risks were highest among people at least 65 years old, the researchers said.

Proton pump inhibitors (PPIs) have been linked previously with causing kidney disease, including AKI.

“Although PPIs are one of the most commonly prescribed medications, 25% to 70%

of these prescriptions are estimated to have no appropriate indication,” Emily Hart, PharmD, and colleagues from the department of pharmacy practice at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, wrote. “Indications such as gastroesophageal reflux disease require only short-term treatment with PPIs (ie, up to 4 to 8 weeks), but chronic use appears to be common. About 40% to 55% of primary care patients and up to 65% of hospitalized patients have no documented ongoing indications for PPIs. Consequently, patients often take these medications without benefit and are therefore subject to unnecessary adverse events.”

The researchers looked at the medical history of adult patients with no evidence of pre-existing renal disease and who were started on PPI therapy and continuously enrolled in a Western New York HMO for at least 12 months between July 1993 and September 2008. Kidney health was compared between patients who underwent PPI therapy and a control group. Examined PPIs included esomeprazole (Vimovo, Horizon Pharma), lansoprazole (Prevacid, TAP Pharmaceuticals), omeprazole (Prilosec, AstraZeneca), pantoprazole (Protonix, Pfizer) and rabeprazole (Aciphex, Eisai Inc.).

In the AKI cohort, there were 148 events among 16,593 patients exposed to PPIs and 67 events among 76,742 unexposed patients. In the CKD cohort, there were 2,370 events among 14,514 PPI users and 4,501 events among 70,086 nonusers.

“This study adds to a growing list of concerning side effects and adverse outcomes associated with PPIs,” David Jacobs, PharmD, PhD, a co-author on the study and assistant professor of pharmacy practice in the University of Buffalo’s School of Pharmacy and Pharmaceutical Sciences, said in a press release. “Given the increasing global use of PPIs, the relationship between PPIs and renal disease could pose a substantial disease and financial burden to the health care system and public health.” – by Mark E. Neumann

Reference:

www.buffalo.edu/news/releases/2019/03/0220.html

Disclosures: Jacobs reports support from the NIH/National Heart, Lung, and Blood Institutes Loan Repayment Program (1 L30 HL138791-01). The research was supported in part by the National Center for Advancing Translational Sciences award UL1 TR001412 to the University at Buffalo. The other study co-authors report no relevant financial disclosures.

Perspective

Leanna Tyshler, MD

In this article, Hart and colleagues report strong associations between use of PPIs and prevalence of AKI, CKD and ESRD. Though this was a retrospective cohort study, it adds to previously reported findings suggestive of association with PPI use and kidney disease. While it is known that PPIs can cause AKI, presumably due to acute interstitial nephritis, the mechanism of chronic kidney injury is less defined. In this study, the effect of PPIs does not appear to be dose or duration dependent. We also don’t know which patients are at risk of developing renal complications from PPI use.

PPIs are widely available, easily accessible for patients and commonly used. Therefore we, as kidney care providers, have a responsibility to educate our patients on potential risks associated with PPI use. It may be worthwhile to monitor renal function in patients on PPIs and establish a low threshold for discontinuing PPIs when patients present with signs of renal dysfunction

Leanna Tyshler, MD

CKD and clinical quality initiatives medical advisor administration

Northwest Kidney Centers

Seattle

Nephrology News & Issues Editorial Advisory Board member

Disclosures: Tyshler reports no relevant financial disclosures.

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Sources/Disclosures

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Source:

Hart E, et al. Pharmacotherapy. 2019;doi:https://doi.org/10.1002/phar.2235.