Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation

• DOI: 10.1371/journal.pmed.1001577
• Publication Date: 2013-12-31T21:32:08Z
• Authors: Kiichi Nakahira; Sun-Young Kyung; Angela J. Rogers; Lee Gazourian; Sojung Youn; Anthony F. Massaro; Carolina Quintana; Juan C. Osorio; Zhaoxi Wang; Yang Zhao; Laurie A. Lawler; Jason D. Christie; Nuala J. Meyer; Finnian R. Mc. Ca...; Sushrut S. Waikar; Aaron B. Waxman; Raymond T. Chung; Raphael Bueno; Ivan O. Rosas; Laura E. Fredenburgh; Rebecca M. Baron; David C. Christiani; Gary M. Hunninghake; Augustine M. K. Choi
• Keywords: Male; 0301 basic medicine; Critical Care and Emergency Medicine; R; 610; Middle Aged; DNA, Mitochondrial; 3. Good health; Intensive Care Units; 03 medical and health sciences; Respiratory Failure; Sepsis; Medicine; Humans; Female; Hospital Mortality; Prospective Studies; Biomarkers; Research Article; Aged

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 biomarker in intensive care unit (ICU). We hypothesized that circulating cell-free levels would be associated with mortality improve risk prediction ICU patients.Analyses were performed on blood samples obtained from two prospective observational cohort studies patients (the Brigham Women's Hospital Registry Critical Illness [BWH RoCI, n = 200] Molecular Epidemiology Acute Respiratory Distress Syndrome [ME ARDS, 243]). plasma assessed by measuring copy number NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical an elevated (≥3,200 copies/µl plasma) had increased odds dying within 28 d admission both BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6-15.8, p 1×10(-7)) ME ARDS (OR 8.4, 2.9-24.2, 9×10(-5)) cohorts, while no evidence association was noted non-medical patients. The addition improved net reclassification index (NRI) 28-d among medical when added to clinical models (NRI 79%, standard error 14%, p<1×10(-4)) 55%, 20%, 0.007) cohorts. In cohort, those death, even analyses limited sepsis or acute respiratory distress syndrome. Study limitations include lack data elucidating concise pathological roles patients, numbers measurements some biomarkers.Increased are mortality, inclusion improves Our suggest could serve viable