title: Cathelicidin antimicrobial protein, vitamin D, and risk of death in critically ill patients.
abstract: BACKGROUND
  Decreased production of cathelicidin antimicrobial protein-18 (hCAP18) has been proposed to be a key mechanism linking decreased 25-hydroxyvitamin D (25D) levels with adverse outcomes among critically ill patients. However, few studies in humans have directly assessed plasma hCAP18 levels, and no study has evaluated the association between hCAP18 levels and adverse outcomes among critically ill patients.
  
  
  METHODS
  We performed a single-center, prospective cohort study among 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012. We measured plasma hCAP18, 25D, D-binding protein, and parathyroid hormone levels on ICU day 1. The primary endpoint was 90-day mortality. Secondary endpoints included hospital mortality, sepsis, acute kidney injury, duration of mechanical ventilation, and hospital length of stay.
  
  
  RESULTS
  ICU day 1 hCAP18 levels were directly correlated with 25D levels (Spearman's rho (rs) = 0.30, P = 0.001). In multivariate analyses adjusted for age and Acute Physiology and Chronic Health Evaluation II (APACHE II) score, patients with hCAP18 levels in the lowest compared to highest tertile on ICU day 1 had a 4.49 (1.08 to 18.67) greater odds of 90-day mortality, and also had greater odds of sepsis. ICU day 1 levels of other analytes were not associated with 90-day mortality.
  
  
  CONCLUSIONS
  Lower 25D levels on ICU day 1 are associated with lower hCAP18 levels, which are in turn associated with a greater risk of 90-day mortality. These findings provide a potential mechanistic basis for the frequently observed association between low 25D levels and poor outcomes in critically ill patients.
authors.affiliation: Division of Renal Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. deleaf@partners.org.
authors.forename: David E
authors.initials: DE
authors.lastname: Leaf
authors.affiliation: Division of Renal Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. hcroy@partners.org.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Croy
authors.affiliation: Division of Renal Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. sabrahams@partners.org.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Abrahams
authors.affiliation: Division of Renal Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. anasraed85@hotmail.com.
authors.forename: Anas
authors.initials: A
authors.lastname: Raed
authors.affiliation: Division of Renal Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. swaikar@partners.org.
authors.forename: Sushrut S
authors.initials: SS
authors.lastname: Waikar
mesh_terms: D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016638:Critical Illness / Q000401:mortality*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D010281:Parathyroid Hormone; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D054804:Cathelicidins