Proton Pump Inhibitors Are Not Associated With Acute Kidney Injury in Critical Illness

Recent epidemiologic data linking proton pump inhibitor (PPI) use to acute and chronic kidney dysfunction is yet to be validated in other populations, and mechanisms have not been explored. Using a large, well phenotyped inception cohort of 15 063 critically ill patients, we examined the risk of acute kidney injury (AKI), as defined by the Kidney Disease Improving Global Outcomes criteria guidelines, according to prior use of a PPI, histamine‐2 receptor antagonist (H2RA), or neither. A total of 3725 (24.7%) patients reported PPI use prior to admission, while 905 (6.0%) patients reported H2RA use. AKI occurred in 747 (20.0%) and 163 (18.0%) of PPI and H2RA users respectively, compared to 1712 (16.2%) of those not taking acid suppressive medications. In unadjusted analysis, PPI and H2RA users had a 28% (95%CI 1.17‐1.41, P < .001) and 10% (95%CI 0.91‐1.30, P = .31) higher risk of AKI compared to those taking neither class of medication. However, in sequential models that included adjustment for demographics, cardiovascular comorbidities, indications for PPI use, and severity of illness, the effect of PPI on the risk of AKI was attenuated, and in the adjusted analysis, PPI was not associated with AKI (OR 1.02; 95%CI 0.91‐1.13, P = .73). The presence of sterile pyuria and hypomagnesemia did not modify the association between PPI use and AKI. In summary, after adjustment for demographics, illness severity, and the indication for PPI use, PPI use prior to admission is not associated with critical illness AKI.