Proton pump inhibitors and the risk of hospital-acquired acute kidney injury in children

Abstract

INTRODUCTION: Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide and have been linked to acute kidney injury (AKI) in adults. However, the effect of PPIs on the risk of AKI in children has not been well studied. METHODS: We conducted a multicenter cohort study in hospitalized children aged 1 month to 18 years from 25 tertiary hospitak across Chbia during 2013-2015. Patientlevel data were obtained from the electronic hospitalization iaformation system. The outcome was hospital-acquired (HA-) AKI. AKI was defined as an increase in serum creatinine (SCr) by 26.5 umol/L (0.3 mg/dl) within 48 hours or a 50% increase in SCr from the baseline within seven days according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Patients who developed AKI after at least two days of admission were identified as having HA-AKL Multiple sensitivity analyses, including propensity score matching, were performed to evaluated the consistency and robustness of the findings from our study. RESULTS: Among 42,374 hospitalized children who met the inclusion and exclusion criteria, induding 10,715 PPI users (25.2%), 1666 histamine 2 receptor antagonist (H2RA) users (4.0%) and 29,993 non-users (70.8%), a total of3529 HA-AKI events (8.3%) were identified. Over 90% of PPIs were prescribed for prophylaxis of gastroduodenal lesions in children need for intensive care or received operation. Compared with non-users and H2RA users, PPI users had a 37% (Odds Ratio [OR] ,1.37; 95% CI, 1.23-1.53) and a24% increased (OR, 1.24; 95% CI, 1.01-1.53) risk of HA-AKI, respectively. The associations were consistent across different subgroups of children, subtypes of PPIs and methods of administration. Children with chronic kidney disease or those taking non-steroid anti-inflammatory drugs had an higher odds of PPI-related AKI. The effect of PPIs on the risk of HA-AKI was dose-independent. Sensitivity analyses showed consistent associations between PPI use and a higher risk of HA-AKI. CONCLUSIONS: PPIs were widely used and associated with an increased risk of HAAKI in hospitalized children. These results call for appropriate prescriptions of PPIs in children worldwide. (Table Presented) .