Risk and Timing of De Novo Sepsis in Critically Ill Children Following Acute Kidney Injury

Background: Acute kidney injury (AKI) is common among critically ill children and is associated with an increased risk for de novo infection, however little is known about the epidemiology and temporal relationship between AKI and AKI-associated infection in this cohort. Methods: We conducted a single-center retrospective cohort study of children admitted to the pediatric and cardiac ICUs at a tertiary pediatric care center. The relationship between non-septic AKI and the development of hospital-acquired sepsis was assessed using Cox proportional-hazards models using AKI as a time-varying covariate. Results: Among the 5695 children included in the study, AKI occurred in 20.2% from ICU admission through 30 days. Hospital-acquired sepsis occurred twice as often among children with AKI compared to those without AKI (10.1% vs. 4.6%) with an adjusted hazard ratio of 1.42 (95% CI 1.12-1.81). Among the 117 children who developed sepsis following AKI, 80.3% developed sepsis within 7 days and 96.6% within 14 days of AKI onset, with a median time from AKI onset to sepsis of 2.6 days (IQR 1.5-4.7). When assessing change in risk over time, the hazard rate for sepsis remained elevated for children with stage 3 AKI compared to children without AKI at 13.5 days following AKI onset, after which the estimation of hazard rates was limited by the number of children remaining in the hospital. Conclusions: AKI is an independent risk factor for de novo sepsis. Critically ill children with stage 3 AKI remain at increased risk for sepsis at 13.5 days following AKI onset.