Proton Pump Inhibitors Increase Risk of Developing CKD

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Using proton pump inhibitors (PPIs) increases the risk of developing chronic kidney disease (CKD) or kidney failure by 33%, according to a meta analysis presented at Kidney Week.

PPIs are one of the most commonly prescribed medications worldwide. They are used to treat gastroesophageal reflux disease (GERD). But a growing number of studies have linked them to serious adverse effects including kidney disease, fractures, Clostridium difficile infections, and vitamin deficiencies (Wilhelm SM, et al. Expert Rev Clin Pharmacol 2013; 6:443–451).

To assess the potential kidney risks, Charat Thongprayoon, MD, of the Bassett Medical Center in Cooperstown, New York, and his colleagues analyzed data from studies that compared the risk of developing CKD or kidney failure among PPI users and non-users. They included 5 studies with 536,902 participants. The relative risk of kidney disease was one-third higher among PPI users (RR 1.33 95% CI, 1.18–1.51).

“This study demonstrates a significant association between the use of PPIs and increased risks of chronic kidney disease and kidney failure,” said Thongprayoon.

He acknowledged that such observational data cannot prove that PPIs cause kidney injury, but he said the evidence is compelling enough to warrant more cautious use of these drugs.

“Although no causal relationship has been proven, providers should consider whether PPI therapy is indicated for patients,” Thongprayoon said. “Chronic use of PPIs should be avoided if not really indicated.”

Nephrologist Ziyad Al-Aly, MD, director of clinical epidemiology at VUS Department of Veterans Affairs St. Louis Health Care System, said the meta analysis helps synthesize the evidence to date linking PPIs with kidney disease. He noted there are a variety of potential mechanisms that might explain kidney-related adverse events in PPI users. The most plausible is that the drugs impair the ability of organelles called lysosomes, which act as the cell’s “garbage incinerator,” he explained.

“They impair the action of those organelles and they accelerate aging of the cells,” he said.

Currently, many physicians who prescribe PPIs monitor their patients for signs of acute kidney injury, Al-Aly noted. However, a recent study by Al-Aly and his colleagues showed that even PPI-using patients without signs of acute kidney injury may be at risk of renal disease (Xie Y, et al. Kidney Int 2017; 91:1482–1494).

“It could be happening insidiously without that warning sign,” he said.

He agreed that more caution should be used in prescribing these drugs. When they are indicated, such as when a patient has a bleeding ulcer, he said the lowest dose should be used for the shortest duration of time. He questioned why the drugs are being so widely prescribed and used, noting that data suggest 30–60% of PPI users may not need the drugs.

“When people who don’t have a medical need to be on a PPI in the first place, all they are getting is the side effects,” he said. “In that instance, the risks outweigh the benefits.”

“Proton Pump Inhibitors and Risk of Chronic Kidney Diseases: A Meta-Analysis” (Abstract 2763180)