Ibuprofen Use and Acute Kidney Injury Among Adults Admitted to the Hospital

Importance Although nonsteroidal anti-inflammatory drugs (NSAIDs) are the most effective nonopioid analgesics for acute pain, they may be underused in the inpatient setting due to uncertainty regarding the risk of acute kidney injury (AKI). Whether inpatient exposure to NSAIDs, such as ibuprofen, substantially increases AKI risk and how ibuprofen-associated AKI varies across patient subgroups remain unknown. Objective To determine whether ibuprofen use is associated with AKI in hospitalized patients and whether the finding varies across AKI risk factor subgroups. Design, Setting, and Participants A retrospective active-comparator cohort study of hospitalized patients (aged ≥18 years) without end-stage kidney disease or contraindications to NSAID treatment admitted from January 1, 2004, to June 30, 2017, in a large academic health system including 3 hospitals in Philadelphia, Pennsylvania, with follow-up until 48 hours after treatment end, hospital discharge, or 14 days elapsed, whichever occurred first. Analyses were conducted from March 2023 through August 2026. Exposures At least 24 hours of treatment with ibuprofen or oxycodone for acute pain. Main Outcomes and Measures The primary outcome was AKI, defined by changes in serum creatinine and incident kidney replacement therapy (KRT). Balancing weights were used to adjust for baseline covariates and weighted Poisson regression used to estimate incidence rate ratios (IRRs) and 95% CIs. Results This study included 78 656 patients (median age, 59 [IQR, 47-69] years; 38 092 females [48%]) treated with ibuprofen (n = 6313) or oxycodone (n = 72 343). There were 4799 AKI events (79% stage 1) during 270 472 days of follow-up (17.7 events per 1000 days). After adjustment for baseline differences, patients treated with ibuprofen had a higher rate of any AKI (IRR, 1.22; 95% CI, 1.09-1.38), severe AKI (IRR, 1.36; 95% CI, 1.08-1.72), and KRT (IRR, 3.29; 95% CI, 1.35-8.03). IRRs were greater in postoperative (IRR, 1.70 [95% CI, 1.28-2.27] vs 1.12 [95% CI, 0.98-1.28]) and critically ill (IRR, 1.65 [95% CI, 1.29-2.11] vs 1.16 [95% CI, 1.02-1.33]) patients. In patients at low risk (those non–critically ill, nonpostoperative, aged <60 years without kidney dysfunction; ibuprofen, n = 2966; oxycodone, n = 20 440), ibuprofen was not associated with higher AKI risk (IRR, 0.94; 95% CI, 0.75-1.18). Conclusions and Relevance This study in an inpatient cohort found that ibuprofen was associated with higher rates of AKI and KRT, but this excess risk was concentrated in patients at high risk. Patients at low risk may be able to receive ibuprofen safely yet were often prescribed oxycodone.