title: Urinary Glycosaminoglycans Predict Outcomes in Septic Shock and Acute Respiratory Distress Syndrome.
abstract: Degradation of the endothelial glycocalyx, a glycosaminoglycan (GAG)-rich layer lining the vascular lumen, is associated with the onset of kidney injury in animal models of critical illness. It is unclear if similar pathogenic degradation occurs in critically ill patients.
  
  
  
  To determine if urinary indices of GAG fragmentation are associated with outcomes in patients with critical illnesses such as septic shock or acute respiratory distress syndrome (ARDS).
  
  
  
  We prospectively collected urine from 30 patients within 24 hours of admission to the Denver Health Medical Intensive Care Unit (ICU) for septic shock. As a nonseptic ICU control, we collected urine from 25 surgical ICU patients admitted for trauma. As a medical ICU validation cohort, we obtained serially collected urine samples from 70 patients with ARDS. We performed mass spectrometry on urine samples to determine GAG (heparan sulfate, chondroitin sulfate, and hyaluronic acid) concentrations as well as patterns of heparan sulfate/chondroitin sulfate disaccharide sulfation. We compared these indices to measurements obtained using dimethylmethylene blue, an inexpensive, colorimetric urinary assay of sulfated GAGs.
  
  
  
  In septic shock, indices of GAG fragmentation correlated with both the development of renal dysfunction over the 72 hours after urine collection and with hospital mortality. This association remained after controlling for severity of illness and was similarly observed using the inexpensive dimethylmethylene blue assay. These predictive findings were corroborated using urine samples previously collected at three consecutive time points from patients with ARDS.
  
  
  
  Early indices of urinary GAG fragmentation predict acute kidney injury and in-hospital mortality in patients with septic shock or ARDS. Clinical trial registered with www.clinicaltrials.gov (NCT01900275).
authors.affiliation: 1 Department of Medicine, and.|2 Department of Medicine, University of Colorado Denver, Aurora, Colorado; and.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Schmidt
authors.affiliation: 1 Department of Medicine, and.
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Overdier
authors.affiliation: 3 Department of Chemistry, and.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Sun
authors.affiliation: 3 Department of Chemistry, and.
authors.forename: Lei
authors.initials: L
authors.lastname: Lin
authors.affiliation: 3 Department of Chemistry, and.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Liu
authors.affiliation: 2 Department of Medicine, University of Colorado Denver, Aurora, Colorado; and.
authors.forename: Yimu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 4 Department of Surgery, Denver Health Medical Center, Denver, Colorado.
authors.forename: Lee Anne
authors.initials: LA
authors.lastname: Ammons
authors.affiliation: 1 Department of Medicine, and.
authors.forename: Terra D
authors.initials: TD
authors.lastname: Hiller
authors.affiliation: 5 Department of Biology, Rensselaer Polytechnic Institute, Troy, New York.
authors.forename: Matt A
authors.initials: MA
authors.lastname: Suflita
authors.affiliation: 3 Department of Chemistry, and.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Yu
authors.affiliation: 3 Department of Chemistry, and.
authors.forename: Yin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 3 Department of Chemistry, and.
authors.forename: Fuming
authors.initials: F
authors.lastname: Zhang
authors.affiliation: 4 Department of Surgery, Denver Health Medical Center, Denver, Colorado.
authors.forename: Clay
authors.initials: C
authors.lastname: Cothren Burlew
authors.affiliation: 2 Department of Medicine, University of Colorado Denver, Aurora, Colorado; and.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Edelstein
authors.affiliation: 1 Department of Medicine, and.|2 Department of Medicine, University of Colorado Denver, Aurora, Colorado; and.
authors.forename: Ivor S
authors.initials: IS
authors.lastname: Douglas
authors.affiliation: 3 Department of Chemistry, and.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003120:Colorado; D006025:Glycosaminoglycans / Q000652:urine*; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D013058:Mass Spectrometry / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012772:Shock, Septic / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000652:urine*; D015599:Trauma Severity Indices; D014947:Wounds and Injuries / Q000145:classification / Q000601:surgery / Q000652:urine*
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans
keywords: chondroitin sulfate; glycocalyx; glycomics; heparan sulfate; hyaluronic acid