Abstract: SA-OR10
Neutrophil Extracellular Traps and Endothelial Injury in COVID-19 Associated AKI
Session Information
- COVID-19 and Kidney Diseases: From Bedside to Bench
November 06, 2021 | Location: Simulive, Virtual Only
Abstract Time: 04:30 PM - 06:00 PM
Category: Coronavirus (COVID-19)
- 000 Coronavirus (COVID-19)
Authors
- Pode shakked, Naomi, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
- Henry, Brandon M., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
- Benoit, Stefanie W., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Background
Neutrophil Extracellular Traps (NETs) release has been implicated in the pathomechanism underlying severe end-organ damage in COVID-19. While NETs are difficult to measure, cell free DNA (cfDNA) has been shown to be a surrogate measure for NETosis. The aim of this study was to determine whether circulating levels of cfDNA may be associated with development of acute kidney injury (AKI) in COVID-19.
Methods
Blood samples were collected prospectively in the emergency department from adult patients admitted to the hospital with COVID-19. cfDNA levels and serum biomarkers of AKI, thrombotic microangiopathy, and inflammation were correlated, as well as development of severe AKI defined by KDIGO SCr Stages 2+3 and need for renal replacement therapy (RRT).
Results
51 patients were enrolled, median age 50.5 years (IQR 41-66). Age, race, coronary artery disease, heart failure, chronic kidney disease, and chronic liver disease were associated with severe AKI, while hypertension was protective. cfDNA levels were higher in those who developed severe AKI (p<0.001) and needed RRT (p=0.020) during hospitalization. cfDNA positively correlated with SCr, NGAL, cystatin C, neutrophil count, neutrophil-to-lymphocyte ratio, C3a, C5a, Scb5-9, IL-6, IL-8, IL-10, TNF-α, LDH, CRP, ferritin, fibrinogen, and negatively correlated with ADAMTS13/VWF ratio and lymphocyte count. In the multivariable logistic regression model adjusted for age, comorbidities, and SCr, one unit increase in cfDNA value was associated with a 4.6% increased odds of severe AKI (OR=1.046; p=0.040). Diagnostic performance of cfDNA is shown in Table 1.
Conclusion
Intravascular NETosis could be an important factor in development of microthrombosis and COVID-19 associated AKI. Further research is urgently needed to understand the role of NETosis in COVID-19 and evaluate therapeutic avenues.
Diagnostic Performance of cfDNA for COVID-19 AKI
| cfDNA Cut-Off (ng/mL) | Sensitivity | Specificity | AUC (95%CI) | |
| Severe AKI | 161.3 | 0.67 | 0.92 | 0.82 (0.67-0.97) |
| Need for RRT | 142.0 | 0.75 | 0.77 | 0.76 (0.54-0.98) |