Circulating mitochondrial DNA in patients in the ICU as a marker of mortality: derivation and validation. Academic Article uri icon

Overview

MeSH

  • Aged
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies

MeSH Major

  • Biomarkers
  • DNA, Mitochondrial
  • Hospital Mortality
  • Intensive Care Units

abstract

  • Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients. Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness [BWH RoCI, n = 200] and Molecular Epidemiology of Acute Respiratory Distress Syndrome [ME ARDS, n = 243]). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6-15.8, p = 1×10(-7)) and ME ARDS (OR 8.4, 95% CI 2.9-24.2, p = 9×10(-5)) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10(-4)) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers. Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients.

publication date

  • December 2013

has subject area

  • Aged
  • Biomarkers
  • DNA, Mitochondrial
  • Female
  • Hospital Mortality
  • Humans
  • Intensive Care Units
  • Male
  • Middle Aged
  • Prospective Studies

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3876981

Digital Object Identifier (DOI)

  • 10.1371/journal.pmed.1001577

PubMed ID

  • 24391478

Additional Document Info

start page

  • e1001577; discussion e1001577

volume

  • 10

number

  • 12