Abstract: SA-PO624
Retrospective Population Scale Analysis Reveals Associations of Proton-Pump Inhibitor Use with Kidney Related Disorders
Session Information
- Pharmacology
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Makunts, Tigran, UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences , La Jolla, California, United States
- Cohen, Isaac V., UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences , La Jolla, California, United States
- Abagyan, Ruben, UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences , La Jolla, California, United States
- Awdishu, Linda, UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences , La Jolla, California, United States
Background
Proton pump inhibitors (PPIs) are one of the most widely prescribed and sold drugs globally. Recent studies have revealed associations between PPI use and acute kidney injury (AKI), chronic kidney disease (CKD), and end stage renal disease (ESRD). The growing concern over potentially serious adverse events (AE) associated with their use warrants an evaluation of post marketing surveillance.
Methods
This is a retrospective study of 9.5 million voluntary adverse event (AE) reports to the FDA Adverse Event Reporting System (FAERS) from January 2004 to August 2017. Two cohorts were constructed from these reports: (1) PPI (n=665,735) and (2) histamine receptor antagonists (H2RA) (n=124,251) cohorts. Any report of patients taking concurrent nephrotoxins or where age was not reported was excluded resulting in 150,361 PPI and 29,115 H2RA AE reports. Outcomes were CKD, AKI, ESRD, nephrolithiasis and electrolyte disorders (hypomagnesemia, hypocalcemia and hypokalemia) defined by coding data. Frequencies of all reported AEs and corresponding odds ratios (OR) were calculated in each cohort.
Results
Patients who received PPIs had a significant increase in the number of reports for CKD OR 1.87 95% CI [1.3, 2.7], AKI 1.23 [1.1, 1.4], nephrolithiasis 2.16 [1.6, 2.9], hypomagnesemia 2.62 [2, 3.4], and hypocalcemia 1.95 [1.5, 2.5]. There was no significant difference in the frequency of hypokalemia 1.15 [0.91, 1.5] and ESRD 7.17 [0.99, 52]. Significant increases in CKD reports were identified for omeprazole 1.89 [1.3, 2.8], esomeprazole 1.95 [1.3, 2.9], dexlansoprazole 10.65 [3.3, 35]. Omeprazole and pantoprazole were significantly associated with increased AKI reports, 1.54 [1.4, 1.7] and 1.64 [1.4, 1.9], respectively whereas esomeprazole had a decrease in AKI reports 0.85 [0.75, 0.96].
Conclusion
In this study, we replicated the association between PPI exposure and the increased risk of AKI, CKD and electrolyte abnormalities from the AE reports in the FAERS database. To our knowledge this is the first large scale study showing a significant association of PPI use with nephrolithiasis. We found differences in AE reporting risk for individual PPIs. Further studies evaluating individual drug effects are warranted to confirm these findings.