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

Abstract

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.

Critical illness myopathy and trajectory of recovery in acute kidney injury requiring continuous renal replacement therapy: a prospective observational trial protocol

“…5 After discharge, AKI survivors are at increased risk of developing chronic kidney disease (CKD), end-stage kidney disease, cardiovascular disease and death. 6 Other studies suggest that AKI predisposes to disparate sources of morbidity including infection, [7][8][9][10] bone fracture, 11 stroke, 12 gastrointestinal haemorrhage 13 and dementia. 14 While muscle wasting is well described in patients with CKD, 15 16 the contribution of AKI-RRT to muscle wasting in critically ill patients has not been previously studied.…”

Sepsis and AKI: A Two-Way Street

“…In this issue of Kidney360 , Formeck and colleagues 8 fill this gap in knowledge by evaluating the temporal relationship of sepsis after an AKI event in 5695 children admitted to pediatric and cardiac intensive care units (ICU) at a tertiary care center between 2010 and 2014. AKI occurred in 20% ( N =1153) of children.…”

“…The pediatric timeline for sepsis development post-AKI is similar to that reported in adults and neonates. 3 , 6 Formeck et al 8 found that sepsis occurred at a median of 2.6 (1.5–4.7) days post-AKI, with 80% developing sepsis within 7 days and 97% within 2 weeks of AKI. Significant risk factors for development of sepsis post-AKI included surgery before ICU admission, male sex, higher severity of illness scores within 24 hours of ICU admission, leukopenia, and the presence of an indwelling central line.…”

“…Significantly, Formeck et al 8 point out that the risk for sepsis remained high for up to 2 weeks after AKI by which time approximately two-third of the patients had recovered kidney function on the basis of return of creatinine to baseline. These data mirror the evidence reported in adults who maintain a significant risk of infection despite the recovery of serum creatinine to baseline and further strengthen the clinical evidence of ongoing immunocompromise well past the recovery of creatinine to baseline.…”

“…Often the factors that increase the risk of AKI are the same that increase the risk of infection. Formeck and colleagues 8 tried to account for potential confounders, such as severity of illness, surgery, and history of malignancy, in their analysis plan using a time-varying Cox model of sepsis development. While surgery before ICU admission, severity of illness scores, leukopenia, and indwelling central lines were significant risk factors for sepsis, AKI, at any stage, remained an independent predictor of sepsis development.…”