In the Journals

Proton pump inhibitors may increase risks of AKI, CKD

Proton pump inhibitor use was associated with increased risks for acute kidney injury and chronic kidney disease, according to a published study.

“Although initially intended for time-limited treatment of acute disorders, such as gastric ulcers and esophagitis, [proton pump inhibitors] PPIs are now commonly used for prolonged durations and are considered safe for over-the-counter access,” Tigran Makunts, of the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego, and colleagues wrote. “Recent studies have raised concern over associations between PPI use and AKI, CKD, ESRD and electrolyte abnormalities. In this study of over 10 million FDA Adverse Event Reporting System records, we provided evidence of kidney injury and electrolyte imbalances in an alarming number of patients taking PPIs.”

To evaluate the frequencies of reported adverse events related to kidney injury and electrolyte disturbances in patients taking PPIs, researchers combined reports from the FDA Adverse Event Reporting System and the FDA Safety Information and Adverse Event Reporting Program. These reports were divided into either the PPI-only cohort (n = 42,537) or the H2RA-only cohort (n = 8,309). The renal adverse drug reaction frequencies of both the PPI-only cohort and the H2RA-only cohort were compared.

Researchers then further split the PPI-only cohort into individual PPI cohorts which consisted of omeprazole (n = 7,749), esomeprazole (n = 27,053), pantoprazole (n = 3,651), lansoprazole (n = 3,360) and rabeprazole (n = 724). The renal adverse drug reaction frequency of each group was also compared to the H2RA-only cohort.

Researchers found that, compared to those who took H2RAs, patients who used PPIs had a greater incidence of CKD (OR = 28.4; 95% CI, 12.7-63.5), AKI (OR = 4.2; 95% CI, 2.8-6.3) and ESRD (OR = 35.5; 95% CI, 5-250).

Proton pump inhibitors 
Proton pump inhibitor use was associated with increased risks for acute kidney injury and chronic kidney disease.
Source: Adobe Stock

When examining the renal adverse drug reaction frequency of each individual PPI, researchers observed an increase in the incidence of AKI with omeprazole, esomeprazole, pantoprazole and lansoprazole, while patients who received omeprazole, esomeprazole or lansoprazole had an increased incidence of CKD and ESRD.

Finally, it was determined that all five of the PPIs were associated with an increase in electrolyte imbalance.

“The observed increased risks of renal and electrolyte adverse effects of PPIs warrant more careful consideration in clinical practice,” the researchers wrote. “The risk-benefit ratio should be considered for the individual patient with respect to the adverse effects. When clinically indicated, PPIs should be used for the shortest duration necessary and chronic use is not recommended except for treatment of pathological hypersecretory conditions ... and maintenance healing of erosive esophagitis.” – by Melissa J. Webb

Disclosures: The authors report no relevant financial disclosures.

Proton pump inhibitor use was associated with increased risks for acute kidney injury and chronic kidney disease, according to a published study.

“Although initially intended for time-limited treatment of acute disorders, such as gastric ulcers and esophagitis, [proton pump inhibitors] PPIs are now commonly used for prolonged durations and are considered safe for over-the-counter access,” Tigran Makunts, of the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego, and colleagues wrote. “Recent studies have raised concern over associations between PPI use and AKI, CKD, ESRD and electrolyte abnormalities. In this study of over 10 million FDA Adverse Event Reporting System records, we provided evidence of kidney injury and electrolyte imbalances in an alarming number of patients taking PPIs.”

To evaluate the frequencies of reported adverse events related to kidney injury and electrolyte disturbances in patients taking PPIs, researchers combined reports from the FDA Adverse Event Reporting System and the FDA Safety Information and Adverse Event Reporting Program. These reports were divided into either the PPI-only cohort (n = 42,537) or the H2RA-only cohort (n = 8,309). The renal adverse drug reaction frequencies of both the PPI-only cohort and the H2RA-only cohort were compared.

Researchers then further split the PPI-only cohort into individual PPI cohorts which consisted of omeprazole (n = 7,749), esomeprazole (n = 27,053), pantoprazole (n = 3,651), lansoprazole (n = 3,360) and rabeprazole (n = 724). The renal adverse drug reaction frequency of each group was also compared to the H2RA-only cohort.

Researchers found that, compared to those who took H2RAs, patients who used PPIs had a greater incidence of CKD (OR = 28.4; 95% CI, 12.7-63.5), AKI (OR = 4.2; 95% CI, 2.8-6.3) and ESRD (OR = 35.5; 95% CI, 5-250).

Proton pump inhibitors 
Proton pump inhibitor use was associated with increased risks for acute kidney injury and chronic kidney disease.
Source: Adobe Stock

When examining the renal adverse drug reaction frequency of each individual PPI, researchers observed an increase in the incidence of AKI with omeprazole, esomeprazole, pantoprazole and lansoprazole, while patients who received omeprazole, esomeprazole or lansoprazole had an increased incidence of CKD and ESRD.

Finally, it was determined that all five of the PPIs were associated with an increase in electrolyte imbalance.

“The observed increased risks of renal and electrolyte adverse effects of PPIs warrant more careful consideration in clinical practice,” the researchers wrote. “The risk-benefit ratio should be considered for the individual patient with respect to the adverse effects. When clinically indicated, PPIs should be used for the shortest duration necessary and chronic use is not recommended except for treatment of pathological hypersecretory conditions ... and maintenance healing of erosive esophagitis.” – by Melissa J. Webb

Disclosures: The authors report no relevant financial disclosures.