Abstract: SA-PO104
Kidney Epithelium Origin Cell-Free DNA: A Promising Biomarker in Prediction Sepsis-Induced AKI
Session Information
- AKI: Epidemiology, Risk Factors, Prevention - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 101 AKI: Epidemiology, Risk Factors, and Prevention
Authors
- You, Ruilian, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Quan, Xiangming, GenePlus-Beijing, Beijing, State..., China
- Xia, Peng, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Zhu, Huadong, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Yang, Ling, GenePlus-Beijing, Beijing, State..., China
- Chen, Limeng, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
Background
Sepsis-induced acute kidney injury (SI-AKI) is a common complication of sepsis with high morbidity and mortality, with the diagnosis based on serum creatinine (Scr) and urine volume. Tracing the origin of the kidney epithelium origin cell-free DNA (Kidney-ep cfDNA) using the methylome atlas is a promising diagnostic biomarker for SI-AKI and has not been reported yet.
Methods
We extracted plasma cfDNA from 7 sepsis non-acute kidney injury (SN-AKI) and 9 SI-AKI patients for TET-assisted pyridine borane sequencing, used a reference methylation atlas of 40 cell types to analyze sequence reads to quantitate the relative contribution of cfDNA from different cell types by using the UXM fragment-level deconvolution algorithm. We multiplied the contribution by the total concentration of cfDNA, to obtain the concentration of Kidney-ep derived molecules. We determined the correlation of Kidney-ep cfDNA measures to SI-AKI, and then evaluated the diagnostic value of the Kidney-ep cfDNA. Differential methylation regions (DMR) were analyzed, and then we performed GO/KEGG pathway enrichment analysis using these DMR-related genes.
Results
Compared to healthy controls, all sepsis patients showed significantly elevated concentrations of cfDNA (P < 0.01). Compared to SN-AKI patients, SI-AKI patients had approximately 8.57-fold higher levels of cfDNA, consistent with the disorders of coagulation cfDNA (P = 0.022). The relative contribution and concentration of Kidney-ep cfDNA in SI-AKI patients was higher than in non-AKI patients (P = 0.003). The Area Under Curve (AUC) in differentiating SI-AKI from spesis patients reached 0.9206, which was higher than that of the cfDNA concentration (0.9206 vs. 0.8889). Also, there was a significant negative correlation between the concentration of kidney-ep cfDNA and the number of days after being diagnosed with SI-AKI (R=0.81, P = 0.028). Except for coagulation dysfunction, the concentration of Kidney-ep cfDNA was not affected by age, hypertension or septic shock (P<0.05). The pathways enriched the DMR genes, including complement and coagulation pathway, lymphocyte differentiation, etc.
Conclusion
Our study first showed the kidney-ep cfDNA is a novel biomarker of the SI-AKI diagnosis with real-time functional response.