Approximately 15 million Americans use Proton Pump Inhibitors (PPIs) to treat conditions such as; Gastroesophageal reflux disease (GERD), Dyspepsia, Acid Reflux, Peptic or stomach ulcers. These medications include; Prilosec, Prevacid, AcipHex, Protonix, Nexium, Zegerid, Dexilant, Vimovo.
With over $14 billion in annual sales these are the commonly prescribed drugs in the U.S. and worldwide. These drugs are sold by prescription as well as over the counter and have long been touted as safe and effective with little risk of side effects.
A number of studies, however, have linked PPIs to kidney injury. In December 2014, the FDA required new warnings for proton pump inhibitors indicating that some users of the medications have experienced acute interstitial nephritis (AIN), and inflammation of the kidneys that can lead to chronic and permanent injury.
Evidence suggests, however, that this is not news to the manufacturers.
In October 1991, The American Journal of Medicine reported on a 74 year old woman admitted to the University of Arizona Health Sciences Center because of acute renal failure. She was diagnosed as having drug-induced acute interstitial nephritis due to omeprazole (PPI). The article stated that, "physicians who prescribe omeprazole should be aware of the association of acute interstitial nephritis with omeprazole."
Five years after the initial article, in 1997, additional research highlighted and expounded on the correlation between PPI use and AIN. The report by the European Renal Association-European Dialysis and Transplant Association stressed the need for caution and monitoring particularly of elderly patients on proton pump inhibitors.
In 2004, Nephrology Dialysis Transplantation, reported on a study again linking AIN to proton pump inhibitors. Research continued to accumulate connecting AIN and other kidney injuries to PPI use, however there was no label change or warnings given. By 2007, it was known and accepted that kidney damage is a confirmed injury related to PPI usage.
In 2013, BMC Nephrology reported a study in which "renal disease was positively associated with PPI use" finding in conclusion "Patients with a renal disease diagnosis were twice as likely to have used a previous prescription for a PPI. Therefore, it is necessary for physicians to increase recognition of patient complaints or clinical manifestations of this potentially harmful event in order to prevent further injury." Still the label remained unchanged.
In April 2015, a study published in CMAJ Open indicated that PPIs are an underappreciated cause of acute kidney injury and that users may be 2.5 times more likely to develop kidney injury than non-users. The study involved a review of data on 300,000 patients aged 66 and older who used PPIs between the years of 2002 and 2011. Elderly users were found to be at higher risk for kidney injury and the risk of AIN was tripled for those patients.
The medical journal JAMA Internal Medicine published a study in January 2016 addressing the link between PPIs and chronic kidney disease which may lead to kidney failure and the need for dialysis or kidney transplant. Data on 10,482 participants was reviewed from 1996-2011. The study found a 45% increased risk of chronic kidney disease with the use of PPIs.
Finally, a study released on April 14, 2016 in the Journal of the American Society of Nephrology found that patients taking PPIs had a 96% increased risk of developing kidney failure and a 28% increased risk of kidney disease compared to patients who took an alternative known as histamine H2 receptor blockers. These include Tagamet, Pepcid, and Zantac.