Erin Stenson, MD
Assistant Professor
Cincinnati Children's Hospital
Aurora, CO
Disclosure information not submitted.
Zhiying You, MD, PhD
Associate Research Professor
UC Denver, United States
Disclosure information not submitted.
Ron Reeder, PhD
Associate Professor
University of Utah, United States
Disclosure information not submitted.
Halden Scott, MD, MS
Associate Professor of Pediatrics
University of Colorado School of Medicine
Aurora
Disclosure information not submitted.
Brad Dixon, MD
Associate Professor
Childrens Hospital Colorado, United States
Disclosure information not submitted.
Peter Mourani, MD
Professor
Arkansas Children's Hospital, United States
Disclosure information not submitted.
Title: Complement activation fragments are increased in pediatric sepsis-associated acute kidney injury
INTRODUCTION/HYPOTHESIS: Critically ill children with sepsis-associated acute kidney injury (SA-AKI) suffer from high morbidity and mortality rates, and lack treatment options. Emerging evidence implicates the role of complement activation in SA-AKI pathogenesis, which could potentially be treated with complement inhibitors. The purpose of this study is to evaluate the association between complement activation fragments and SA-AKI in critically ill children.
Methods: A biorepository of critically ill children requiring mechanical ventilation >72 hours from a prior multi-site study was leveraged to identify children with stage 3 AKI (based on serum creatinine KDIGO criteria) and matched to patients without AKI based on PELOD-2 (illness severity) scores. Patients with stage 3 AKI were divided into SA-AKI and non-septic-AKI (non-SA-AKI). Specimens were analyzed for plasma and urine complement activation fragments of factor B (factor Ba and factor Bb), C3a, C4a, and sC5b-9. Kruskal-Wallis test was performed for statistical analysis.
Results: 5 children with stage 3 SA-AKI were compared to 9 children with stage 3 non-SA-AKI and 14 children with no AKI. Urine factor Ba was significantly elevated in SA-AKI patients (median 2280; IQR 881-5013) compared to non-SA-AKI patients (median 422; IQR 215-1257) and no-AKI patients (median 174; IQR 39-542), p = 0.014. There was significant elevation of plasma C4a in patients with SA-AKI (median 1685; IQR 1383-2020) compared to non-SA-AKI (median 1299; IQR 1078-1856) and no AKI (median 474; IQR 235-802), p 0.002. Similar results were seen with plasma C3a levels: SA-AKI (median 362; IQR 143-439); non-SA-AKI (median 144; IQR 100-266); no AKI (median 78; IQR 50-143); p 0.042. Plasma factor Bb and sC5b-9 levels trended in a similar direction but did not reach significance.
Conclusions: Plasma and urine complement activation fragments are significantly increased in patients with SA-AKI compared to non-SA-AKI and no-AKI levels. These pilot findings suggest the need for further specific investigations of the role of complement activation in critically ill children at risk of SA-AKI. Complement activation fragments may identify patients to study complement inhibition to treat or prevent AKI in critically ill, septic children.