Abstract: FR-PO1174
Association of Elevated Circulating Histone-DNA Complex Level with CKD Progression and All-Cause Mortality: Results from CMERC-HI
Session Information
- CKD: Screening, Diagnosis, Serum and Urine Biomarkers, and Scoring Indices
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Joo, Young Su, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Kim, Jwa-kyung, Hallym University Sacred Heart Hospital, Anyang-si, Gyeonggi-do, Korea (the Republic of)
- Ko, Ye Eun, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Kang, Shin-Wook, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Park, Sungha, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
- Yoo, Tae-Hyun, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
Background
Previous studies have demonstrated that neutrophil extracellular traps (NETs) play a causative role in endothelial dysfunction in chronic inflammatory diseases. However, the presence of NETs in patients with chronic kidney disease (CKD) and their association with CKD progression and mortality have not been evaluated. In this study, we investigated the association between circulating histone–DNA complexes (nucleosomes), a surrogate marker of NETs, and the risk of CKD progression and all-cause mortality in patients with CKD.
Methods
A total of 819 participants with CKD were identified from participants in the Cardiovascular and Metabolic disease Etiology Research Center–High Risk (CMERC-HI) study database. Key exclusion criteria included individuals with receiving KFRT at baseline and those with preserved kidney function without proteinuria. Circulating levels of nucleosomes and P-selectin were measured using enzyme-linked immunosorbent assay (ELISA) kits. Participants were stratified by baseline nucleosome levels into Quartiles 1–3 versus Quartile 4. The primary outcome was a composite of CKD progression or all-cause mortality. CKD progression was defined as either a ≥50% decline in estimated glomerular filtration rate (eGFR) from baseline or the initiation of KFRT.
Results
The mean age was 58.4±12.5 years and 54.5% were male. Over 4,567 person-years of follow-up, CKD progression and death occurred in 291 (35.5%) and 89 (10.8%) participants, respectively. In crude Cox regression, elevated nucleosome levels (Quartile 4) were associated with increased risk of the composite outcome compared to Quartiles 1–3 (HR 1.43; 95% CI 1.12–1.83), and this remained significant after adjusting for confounding factors including age, sex, eGFR and proteinuria (HR 1.46; 95% CI 1.14–1.88). High nucleosome levels were also independently associated with CKD progression and mortality when assessed separately. Nucleosome levels showed no correlation with eGFR (r=0.005, P=0.88), but were modestly correlated with P-selectin (r=0.098, P=0.005) in the Pearson correlation analysis.
Conclusion
Presence of NETs is associated with an increased risk of CKD progression and mortality. Elevated nucleosome levels correlated with P-selectin, suggesting that NETs may contribute to kidney injury through endothelial dysfunction.