title: Urinary L-type fatty acid-binding protein as a new biomarker of sepsis complicated with acute kidney injury.
abstract: OBJECTIVE
  This study is aimed to examine whether urinary L-type fatty acid-binding protein can detect the severity of sepsis with animal sepsis models and septic shock patients complicated with established acute kidney injury.
  
  
  METHODS
  Experimental animal models and a clinical, prospective observational study.
  
  
  METHODS
  University laboratory and tertiary hospital.
  
  
  METHODS
  One hundred fourteen human L-type fatty acid-binding protein transgenic mice and 145 septic shock patients with established acute kidney injury.
  
  
  METHODS
  Animals were challenged by abdominal (cecal ligation and puncture) and pulmonary (intratracheal lipopolysaccharide injection) sepsis models with different severities that were confirmed by survival analysis (n = 24) and bronchoalveolar lavage fluid analysis (n = 38).
  
  
  RESULTS
  In animal experiments, significant increases of urinary L-type fatty acid-binding protein levels were induced by sepsis (severe cecal ligation and puncture 399.0 ± 226.8 μg/g creatinine [n = 12], less-severe cecal ligation and puncture 89.1 ± 25.3 [n = 11], sham 13.4 ± 3.4 [n = 10] at 6 hrs, p < .05 vs. sham; 200 μg of lipopolysaccharide 190.6 ± 77.4 μg/g creatinine [n = 6], 50 μg of lipopolysaccharide 145.4 ± 32.6 [n = 8], and saline 29.9 ± 14.9 [n = 5] at 6 hrs, p < .05 vs. saline). Urinary L-type fatty acid-binding protein predicted severity more accurately than blood urea nitrogen, serum creatinine, and urinary N-acetyl-d-glucosaminidase levels. In clinical evaluation, urinary L-type fatty acid-binding protein measured at admission was significantly higher in the nonsurvivors of septic shock with established acute kidney injury than in the survivors (4366 ± 192 μg/g creatinine [n = 68] vs. 483 ± 71 [n = 77], p < .05). Urinary L-type fatty acid-binding protein showed the higher value of area under the receiver operating characteristic curve for mortality compared with Acute Physiology and Chronic Health Evaluation (APACHE) II and Sepsis-related Organ Failure Assessment (SOFA) scores (L-type fatty acid-binding protein 0.994 [0.956-0.999], APACHE II 0.927 [0.873-0.959], and SOFA 0.813 [0.733-0.873], p < .05).
  
  
  CONCLUSIONS
  Our results suggest that urinary L-type fatty acid-binding protein can be a useful biomarker for sepsis complicated with acute kidney injury for detecting its severity.
authors.affiliation: Department of Nephrology and Endocrinology, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, the University of Tokyo, Tokyo, Japan.
authors.forename: Kent
authors.initials: K
authors.lastname: Doi
authors.forename: Eisei
authors.initials: E
authors.lastname: Noiri
authors.forename: Rui
authors.initials: R
authors.lastname: Maeda-Mamiya
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishii
authors.forename: Kousuke
authors.initials: K
authors.lastname: Negishi
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Hamasaki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.forename: Naoki
authors.initials: N
authors.lastname: Yahagi
authors.forename: Hikaru
authors.initials: H
authors.lastname: Koide
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugaya
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications* / Q000175:diagnosis / Q000652:urine; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000652:urine*; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D011446:Prospective Studies; D012772:Shock, Septic / Q000150:complications* / Q000175:diagnosis / Q000652:urine
chemical_list: D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins