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Abstract: TH-PO043

Exosomal Mitochondrial DNA Is a Prognostic Factor in Septic AKI Patients

Session Information

Category: Acute Kidney Injury

  • 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

  • Tsuji, Naoko, Hamamatsu University School of Medicine, Hamamatsu, Japan
  • Tsuji, Takayuki, Hamamatsu University School of Medicine, Hamamatsu, Japan
  • Kato, Akihiko, Hamamatsu University School of Medicine, Hamamatsu, Japan
  • Yasuda, Hideo, Hamamatsu University School of Medicine, Hamamatsu, Japan
Background

We reported the amount of circulating mitochondrial DNA (mtDNA) was increasing in septic rodent models and contributed development of AKI via toll-like receptor 9. The levels of mtDNA in septic patients have varied according to reports, which might occur because of the difference of the blood plasma fraction due to different centrifugal processing. We assayed mtDNA according to blood plasma fractions and evaluated whether mtDNA in circulating exosome was a prognostic factor in septic shock and septic AKI patients.

Methods

Septic patients who needed polymyxin B immobilized hemoperfusion (PMX) in intensive care unit of Hamamatsu University School of Medicine from November 2013 to March 2017 were enrolled. Patient’s plasma was collected from just before the PMX initiation followed by centrifugation at 17,000g for 15 minutes to remove dead cell and cell debris. Exosome was obtained by ultracentrifugation at 200,000g for 1 hour. We extracted exosomal DNA and quantified exosomal mtDNA (Ex-mtDNA) by using real-time PCR. We prospectively observed their outcomes.

Results

The level of Ex-mtDNA in septic shock patients with hospital death (n=6) was significantly higher than those survivors (n=16) and health volunteers (n=4) (log2.80±1.19 vs log0.91±0.81 vs log-0.56±1.09, p<0.05). The ROC curve analysis revealed that Ex-mtDNA is the best prediction for in-hospital death compared with total mtDNA and blood lactic acid and SOFA score and urine volume [AUC: 0.90 (0.74-1.08) vs 0.86 (0.69-1.03), 0.80 (0.58-1.03), 0.84 (0.64-1.06)] and has high sensitivity and specificity and also odds ratio [0.83 (0.36-1.00), 0.93 (0.66-1.00), 65.0 (2.27-125), p<0.05, cut-off value: log1.91] The level of Ex-mtDNA in AKI patients was also higher than those in non-AKI patients (log1.84±1.20 vs log0.63±1.10, p<0.05) but was not better prediction than blood lactic acid and SOFA score [AUC: 0.76 (0.53-1.00) vs 0.82 (0.63-1.01), 0.85 (0.67-1.02)].

Conclusion

Ex-mtDNA has a potential as a good predictor of survival and AKI in septic shock patients.