title: Urinary exosomal activating transcriptional factor 3 as the early diagnostic biomarker for sepsis-induced acute kidney injury.
abstract: An early sepsis-induced acute kidney injury (sepsis-AKI) biomarker is currently in needed. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a candidate of sepsis-AKI biomarker but with different cut-point values. Urinary exosomal activating transcriptional factor 3 (uATF3) has been mentioned as an interesting biomarker.
  
  
  
  We conducted experiments in mice and a prospective, multicenter study in patients as a proof of concept that urine exosome is an interesting biomarker. An early expression of ATF3 in kidney of CD-1 mice at 6 h after cecal ligation and puncture implied the possibility of uATF3 as an early sepsis-AKI biomarker. Increase serum creatinine (Scr) ≥0.3 mg/dL from the baseline was used as an AKI diagnosis and urine was analyzed for uATF3 and uNGAL. Patients with baseline Scr at admission ≥1.5 mg/dL were excluded.
  
  
  
  The analysis showed higher Scr, uNGAL and uATF3 in patients with sepsis-AKI in comparison with patients with sepsis-non-AKI and healthy volunteers. A fair correlation, r2= 0.47, between uATF3 and uNGAL was showed in sepsis-AKI group with Scr ≥2 mg/dL. To see if uATF3 could be an early sepsis-AKI biomarker, urine sample was collected daily during the first week of the admission. In sepsis-AKI and sepsis-non-AKI groups, uNGAL were 367 ± 43 ng/mL and 183 ± 23 ng/mL, respectively; and uATF3 were 19 ± 4 ng/mL and 1.4 ± 0.8 ng/mL, respectively. With the mean value of uNGAL and uATF3 in sepsis AKI as a cut-off level, AUROC of uNGAL and uATF3 were 64% (95% CI 0.54 to 0.74) and 84% (95% CI 0.77 to 0.91), respectively.
  
  
  
  Urine exosome is an interesting source of urine biomarker and uATF3 is an interesting sepsis-AKI biomarker.
authors.affiliation: Immunology Unit, Department of Microbiology, Chulalongkorn University, Bangkok, 10330, Thailand.|Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Tanaporn
authors.initials: T
authors.lastname: Panich
authors.affiliation: Division of Nephrology, Department of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.|Division of Nephrology and Hypertension, Department of Medicine, Princess Chulabhorn College of Medical Sciences, Chulabhorn Royal Academy of Science (CRAS), Bangkok, 10210, Thailand.
authors.forename: Wiwat
authors.initials: W
authors.lastname: Chancharoenthana
authors.affiliation: Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Poorichaya
authors.initials: P
authors.lastname: Somparn
authors.affiliation: Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Jiraphorn
authors.initials: J
authors.lastname: Issara-Amphorn
authors.affiliation: Immunology Unit, Department of Microbiology, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Nattiya
authors.initials: N
authors.lastname: Hirankarn
authors.affiliation: Immunology Unit, Department of Microbiology, Chulalongkorn University, Bangkok, 10330, Thailand. a_leelahavanit@yahoo.com.|Division of Nephrology, Department of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand. a_leelahavanit@yahoo.com.|Center of Excellence in Immunology and Immune-mediated Diseases, Department of Microbiology, Chulalongkorn University, Bangkok, 10330, Thailand. a_leelahavanit@yahoo.com.
authors.forename: Asada
authors.initials: A
authors.lastname: Leelahavanichkul
mesh_terms: D051700:Activating Transcription Factor 3 / Q000652:urine*; D058186:Acute Kidney Injury / Q000175:diagnosis / Q000209:etiology / Q000652:urine*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D055354:Exosomes / Q000378:metabolism; D005260:Female; D006801:Humans; D000071068:Lipocalin-2 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000150:complications / Q000652:urine*
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D003404:Creatinine
keywords: Activating transcriptional factor 3; Acute kidney injury; Biomarker; Neutrophil gelatinase-associated lipocalin; Urine exosome