title: Proteome analysis of hemofilter adsorbates to identify novel substances of sepsis: a pilot study.
abstract: Blood purification therapy using hemofilters with high adsorbing capabilities has been reported to remove excessive humoral mediators from the blood of patients with sepsis. However, there are insufficient studies of the adsorbates bound to hemofilter membranes. We hypothesized that these adsorbates in acute kidney injury (AKI) patients with sepsis were different from those in patients without sepsis and that proteome analysis of the adsorbates would identify novel substances of sepsis. This study included 20 patients who had AKI upon admission to intensive care units (ICUs) and who received continuous renal replacement therapy using polymethyl methacrylate hemofilters. We isolated adsorbates from the hemofilters after use and performed comprehensive proteome analysis. A total of 429 proteins were identified in these adsorbates. Adsorbates from the hemofilters of patients with sepsis had significantly increased frequency of proteins associated with "immune system process" and "biological adhesion" functions compared to those of non-sepsis patients (P < 0.05). Of 429 proteins, 197 were identified only in sepsis adsorbates. Of these, 3 proteins including carbonic anhydrase 1 (CA1) and leucine-rich alpha-2-glycoprotein (LRG1) were identified in all samples from sepsis patients and have not been previously reported in sepsis patients. Validation analysis of patient serum revealed that patients with sepsis had increased serum levels of CA1 and LRG1 compared to patients without sepsis (P < 0.05). To conclude, there were significant differences in the characteristics of the adsorbates from sepsis and non-sepsis patients. CA1 and LRG1 appear to be novel substances associated with sepsis.
authors.affiliation: Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo, Chiba, 260-8677, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hashida
authors.affiliation: Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo, Chiba, 260-8677, Japan. taka.nakada@nifty.com.
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Nakada
authors.affiliation: Division of Clinical Mass Spectrometry, Chiba University Hospital, Chiba, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Satoh
authors.affiliation: Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo, Chiba, 260-8677, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tomita
authors.affiliation: Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo, Chiba, 260-8677, Japan.
authors.forename: Rui
authors.initials: R
authors.lastname: Kawaguchi
authors.affiliation: Division of Clinical Mass Spectrometry, Chiba University Hospital, Chiba, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
authors.affiliation: Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo, Chiba, 260-8677, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Oda
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications* / Q000378:metabolism / Q000628:therapy*; D000327:Adsorption; D000368:Aged; D016022:Case-Control Studies; D003422:Critical Care; D005260:Female; D006440:Hemofiltration; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019904:Polymethyl Methacrylate; D011506:Proteins / Q000032:analysis*; D018805:Sepsis / Q000150:complications* / Q000378:metabolism* / Q000628:therapy
chemical_list: D011506:Proteins; D019904:Polymethyl Methacrylate
keywords: Acute kidney injury; Continuous hemodiafiltration; Critically ill; Infection; Proteomics