title: The Role of Cell-Free Plasma DNA in Critically Ill Patients with Sepsis.
abstract: BACKGROUND
  The identification of highly reliable outcome predictors in severe sepsis is important to define disease severity, predict bedside prognosis and monitor response to treatment. Cell-free plasma DNA (cfDNA) has been recently proposed as a possible prognostic marker of clinical outcome in septic patients. In this study, we investigated the prognostic value of cfDNA in patients with sepsis and its possible correlation with caspase-3, IL-6 and IL-18 levels.
  
  
  METHODS
  We enrolled 34 patients admitted to the intensive care unit (ICU). Out of these 34, 27 patients were septic and 7 were non-septic. cfDNA was extracted from plasma and quantified by real time PCR. Plasma levels of caspase-3, IL-6 and IL-18 were measured by ELISA.
  
  
  RESULTS
  We observed significantly higher levels of cfDNA in septic patients. No significant differences were found between cfDNA levels in patients with Gram+, Gram- and fungal infections. Out of the 27 septic patients, 12 developed acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT), and cfDNA levels resulted to be higher in this group. Out of the 27 septic patients, 11 had a negative outcome during the ICU stay. The cfDNA concentrations at admission were higher in non-survivors than in survivors. Caspase-3, IL-6 and IL-18 levels were significantly higher in septic patients when compared to these levels in non-septic patients and correlated with cfDNA levels.
  
  
  CONCLUSIONS
  cfDNA can be considered a good prognostic marker of clinical outcome in septic patients. Its levels increase in case of AKI complicating sepsis, in particular if CRRT is needed, and are associated with poor outcome. Caspase-3, IL-6 and IL-18 levels are higher in septic patients and correlate to cfDNA concentrations.
authors.affiliation: IRRIV-International Renal Research Institute, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Clementi
authors.forename: Grazia Maria
authors.initials: GM
authors.lastname: Virzì
authors.forename: Alessandra
authors.initials: A
authors.lastname: Brocca
authors.forename: Silvia
authors.initials: S
authors.lastname: Pastori
authors.forename: Massimo
authors.initials: M
authors.lastname: de Cal
authors.forename: Stefano
authors.initials: S
authors.lastname: Marcante
authors.forename: Antonio
authors.initials: A
authors.lastname: Granata
authors.forename: Claudio
authors.initials: C
authors.lastname: Ronco
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D053148:Caspase 3 / Q000097:blood / Q000235:genetics; D016638:Critical Illness; D004247:DNA / Q000097:blood*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007362:Intensive Care Units; D020382:Interleukin-18 / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D017582:Renal Replacement Therapy; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000401:mortality; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; C000589760:IL18 protein, human; C508600:IL6 protein, human; D020382:Interleukin-18; D015850:Interleukin-6; D004247:DNA; C505407:CASP3 protein, human; D053148:Caspase 3