NEUTROPHIL EXTRACELLULAR TRAPS (NETS) AS BIOMARKERS OF ADVERSE OUTCOMES IN CRITICAL ILLNESS-ASSOCIATED AKI

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NEUTROPHIL EXTRACELLULAR TRAPS (NETS) AS BIOMARKERS OF ADVERSE OUTCOMES IN CRITICAL ILLNESS-ASSOCIATED AKI

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Co-author 1

Hesham Kamal Habeeb Keryakos hesham.keryakos@mu.edu.eg Faculty of Medicine, Minia University Department of Internal Medicine and Nephrology El-Minya Egypt *

Co-author 2

Neama Ahmed AbdEl-Aziz neama.ahmed@med.suezuni.edu.eg Faculty of Medicine, Minia University Department of Internal Medicine El-Minya Egypt -

Co-author 3

Amel Mahmoud Kamal El-Din amal.mahmoud@mu.edu.eg Faculty of Medicine, Minia University Department of Clinical Pathology El-Minya Egypt -

Co-author 4

Hesham Abd El-Halim hisham_ali1993@yahoo.com Faculty of Medicine, Minia University Department of Internal Medicine El-Minya Egypt -

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Introduction

Acute kidney injury (AKI) in critical illness carries high mortality and risk of chronic kidney disease (CKD) progression. Neutrophil extracellular traps (NETs) play a role in inflammation and organ damage, but their prognostic role in AKI remains uncleare. We investigated NET levels in AKI patients and their associations with clinical outcomes.

Methods

This prospective observational study enrolled 73 critically ill AKI patients (KDIGO criteria, ICU stay >48 hours) and 33 healthy controls at Minia University Hospital (2022-2024). Exclusion criteria were pre-existing CKD, hematologic malignancies, or immunosuppression. Serum NETs were quantified by ELISA at admission and post-recovery. Primary outcomes were mortality and CKD progression; secondary outcomes included infection rates and length of stay. Correlations with APACHE II scores, inflammatory markers (CRP, WBC), and renal function were analyzed using Spearman’s rank test. ROC curves evaluated prognostic performance.

Results

Fig. 1 AKI patients had significantly higher NETs than controls (median 364 vs 264 pg/mL, p<0.001).

NETs correlated strongly with disease severity (APACHE II: r=0.519, p<0.001), inflammation (CRP: r=0.285, p=0.015; WBC: r=0.481, p<0.001), and renal dysfunction (creatinine: r=0.618, p<0.001).

Non-survivors had 82% higher baseline NETs than survivors (571 vs 313.5 pg/mL, p<0.001).

NETs predicted

• Mortality: AUC=0.838 (cutoff ≥399 pg/mL, 76% sensitivity, 77% specificity)

• CKD progression: AUC=0.919 (follow-up NETs ≥302 pg/mL, 100% sensitivity)

• Bloodstream infections: AUC=0.722 (baseline NETs ≥288 pg/mL)

Persistent NET elevation post-recovery (median 264 vs control 175 pg/mL, p<0.001) suggested ongoing subclinical inflammation.

Conclusion

NETs are elevated in AKI and independently predict mortality, CKD progression, and infections. Their dynamic changes reflect disease severity, offering utility for risk stratification and potential therapeutic targeting.

Kewords