Long-Term PPI Use Linked to Increased Incident CKD Risk

HealthDay News – Duration of proton pump inhibitor (PPI) therapy correlates with increased risk of developing chronic kidney disease (CKD) and CKD progression, according to research published in the Journal of the American Society of Nephrology. These findings are of clinical significance in the practice of rheumatology because many patients are prescribed PPIs to address gastrointestinal effects of corticosteroid use. 

The new study findings are based on medical records from 173,321 Veterans Affairs patients who were prescribed a PPI and 20,270 other patients prescribed a histamine H2-receptor antagonist (H2-blocker).

Over five years, 15% of PPI users were diagnosed with chronic kidney disease, versus 11% of those on H2-blockers. After the researchers weighed other factors, PPI users still had a 28% greater risk. PPI users were also 28% more likely to develop CKD than the H2-blocker group (HR, 1.28; 95% CI, 1.23 – 1.34). Few study patients — less than 0.2% — developed end-stage kidney failure. But the odds were almost doubled among PPI users.

“Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31-90, 91-180, 181-360, and 361-720 days compared with those exposed for ≤30 days,” the authors noted. 

“I think people see these medications at the drug store and assume they’re completely safe,” Ziyad Al-Aly, MD, a kidney specialist with the Veterans Affairs St. Louis Health Care System, told HealthDay. “But there’s growing evidence they’re not as safe as we’ve thought.” 

And, Dr Al-Aly said, the risk increased the longer people used the medications: Patients on PPIs for one to two years had a three-fold higher risk of kidney failure than those who used the drugs for a month or less.

Summary and Clinical Applicability

“The results emphasize the importance of limiting PPI use to only when it is medically necessary, and also limiting the duration of use to the shortest duration possible,” Dr Al-Aly stated in an accompanying news release.


The study does not provide direct causal linkage between PPI use and CKD. The population examined in this study was limited to those enrolled in Veterans Affairs databases.  It also does not address the time frame in which kidney function may recover if PPIs are discontinued once CKD has already occurred. 


Xie Y, Bowe B, Li T, Xian H, Balasubramanian S, Al-aly Z. Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD. J Am Soc Nephrol. 2016; [Epug ahead of print] April 14, 2016, doi:10.1681/ASN.2015121377