Mitochondrial Sirt3 serves as a biomarker for sepsis diagnosis and mortality prediction

Abstract

AbstractThe purpose of this study is to determine whether the levels of serum Sirt3 correlate with disease severity and perfusion indicators in septic patients, as well as to assess the clinical value of Sirt3 as a potential novel marker for sepsis diagnosis and mortality prediction. A total of 79 patients in the ICU were included in the study, of which 28 were postoperatively noninfectious and the remaining 51 patients were all diagnosed with sepsis during the study period. The levels of Sirt3 were detected and dynamically monitored by enzyme-linked adsorption method, Pearson or Spearman coefficient for correlation analysis between Sirt3 and clinical indicators, ROC curve for evaluation of diagnosis and mortality prediction, Kaplan–Meier method for the significance of Sirt3 in 28-day survival. The serum levels of Sirt3 were lower in the sepsis patients on day 1 (P < 0.0001), and the septic shock group had lower Sirt3 levels than the sepsis group (P = 0.013). Sirt3 had good negative correlations with SOFA scores both in sepsis and septic shock groups (Pearson: r2 = − 0.424, − 0.518; P = 0.011, 0.040), and Sirt3 correlated strongly with ScvO2 in the septic shock group (Pearson: r2 = − 0.679, P = 0.004) and with PCT in the sepsis group (Pearson: r2 = − 0.409, P = 0.015). Sirt3 not only performed well in identifying sepsis (AUC = 0.995, 95% CI 0.987–1, P < 0.0001) but also greatly enhanced lactate's specificity in detecting septic shock (from 91.43 to 94.29%). Patients in the low Sirt3 group had higher ScvO2, lactate, APACHE II score, SOFA score, longer ICU stays, and worse indicators of inflammation (TNF-α, IL-6) and infection (PCT) than those in the high Sirt3 group (P < 0.05). Additionally, Sirt3 can predict mortality of sepsis (AUC = 0.746, 95% CI 0.571–0.921, P = 0.022), patients with serum Sirt3 < 10.07 pg/ml have a lower 28-day survival (log-rank P = 0.008). Low serum levels of Sirt3 are significantly correlated with the disease severity. At the same time, Sirt3 increases the sensitivity of lactate to detect “cellular hypoxia” in septic shock. Sirt3 is a promising biomarker for the diagnosis of sepsis and predicting mortality risk in septic patients.