Patients who are taking proton pump inhibitors (PPIs) may be at increased risk for kidney function decline, chronic kidney disease (CKD), and kidney failure, according to a new study published online in the Journal of the American Society of Nephrology.

Proton pump inhibitors, commonly used to treat acid reflux and ulcers, are among the top 10 class of prescribed medications in the U.S. They work by suppressing gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. By acting specifically on the proton pump, these agents block the final step in acid production, thus reducing gastric acidity.

In this study, researchers used the Department of Veterans Affairs national databases to find new users of PPIs and histamine H2-receptor antagonists (H2-blockers); 173,321 PPI users and 20,270 H2-blocker users were included and were followed for over five years to ascertain renal outcomes. Compared to patients who used the H2-blockers, the PPI group had an increased risk of incident eGFR<60mL/min per 1.73m2 (hazard ratio [HR] 1.22; 95% confidence interval [95% CI], 1.18 to 1.26) and of incident CKD (HR 1.28; 95% CI, 1.23 to 1.34).

Related article: Do Acid Reflux Meds Increase CKD Risk? 

The PPI group also had significantly elevated risk of eGFR decline >30% (HR 1.32), end-stage renal disease (ESRD) (HR 1.96), and doubling of serum creatinine level (HR 1.53). In addition, there was a graded association between duration of PPI use and risk of renal outcomes, with those exposed the longest being more likely to develop kidney issues.

“The results emphasize the importance of limiting PPI use only when it is medically necessary, and also limiting the duration of use to the shortest duration possible,” said Dr. Ziyad Al-Aly, one of the team leaders,” A lot of patients start taking PPIs for a medical condition, and they continue much longer than necessary.”

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