title: Plasma Neutrophil Gelatinase-Associated Lipocalin Is Primarily Related to Inflammation during Sepsis: A Translational Approach.
abstract: Acute kidney injury (AKI) during sepsis is common and underestimated. Plasma neutrophil gelatinase-associated lipocalin (plasma-NGAL) is discussed as new biomarker for AKI diagnosis, but during inflammation its function and diagnostic impact remain unclear. The association between plasma-NGAL and inflammatory markers in septic patients, but also in healthy controls and patients with chronic inflammation before and after either maximum exercise test or treatment with an anti-TNF therapy were investigated. In-vitro blood stimulations with IL-6, lipopolysaccharide, NGAL or its combinations were performed to investigate cause-effect-relationship. Plasma-NGAL levels were stronger associated with inflammation markers including IL-6 (Sepsis: r = 0.785 P < 0.001; chronic inflammation after anti-TNF: r = 0.558 P < 0.001), IL-8 (Sepsis: r = 0.714 P<0.004; healthy controls after exercise r = 0.786 P < 0.028; chronic inflammation before anti-TNF: r = 0.429 P < 0.041) and IL-10 (healthy controls before exercise: r = 0.791 P < 0.028) than with kidney injury or function. Correlation to kidney injury or function was found only in septic patients (for creatinine: r = 0.906 P < 0.001; for eGFR: r = -0.686 P = 0.005) and in patients with rheumatic disease after anti-TNF therapy (for creatinine: r = 0.466 P < 0.025). In stimulation assays with IL-6 and lipopolysaccharide plasma-NGAL was increased. Co-stimulation of lipopolysaccharide with plasma-NGAL decreased cellular injury (P < 0.05) and in trend IL-10 levels (P = 0.057). Septic mice demonstrated a significantly improved survival rate after NGAL treatment (P < 0.01). Plasma-NGAL seams to be strongly involved in inflammation. For clinical relevance, it might not only be useful for AKI detection during severe inflammation - indeed it has to be interpreted carefully within this setting - but additionally might offer therapeutic potential.
authors.affiliation: Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany; Clinic for Anesthesiology and Intensive Care, Jena University Hospital, Jena, Germany.
authors.forename: Gordon P
authors.initials: GP
authors.lastname: Otto
authors.affiliation: Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
authors.forename: Jorge
authors.initials: J
authors.lastname: Hurtado-Oliveros
authors.affiliation: Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
authors.forename: Ha-Yeun
authors.initials: HY
authors.lastname: Chung
authors.affiliation: Clinic for Internal Medicine (KIM III)-Rheumatology, Jena University Hospital, Jena, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Knoll
authors.affiliation: Clinic for Internal Medicine (KIM III)-Rheumatology, Jena University Hospital, Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Neumann
authors.affiliation: Department of Sports Medicine and Health Promotion, Friedrich-Schiller-University, Jena, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Müller
authors.affiliation: Department of Sports Medicine and Health Promotion, Friedrich-Schiller-University, Jena, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Herbsleb
authors.affiliation: Department of Medical and Life Sciences, Furtwangen University, Villingen-Schwenningen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kohl
authors.affiliation: Clinic for Internal Medicine (KIM III)-Nephrology, Jena University Hospital, Jena, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Busch
authors.affiliation: Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany; Clinic for Anesthesiology and Intensive Care, Jena University Hospital, Jena, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Sossdorf
authors.affiliation: Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany; Clinic for Anesthesiology and Intensive Care, Jena University Hospital, Jena, Germany.
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Claus
mesh_terms: D000209:Acute-Phase Proteins; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015444:Exercise; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007249:Inflammation / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000293:injuries / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D015513:Oncogene Proteins / Q000097:blood*; D011518:Proto-Oncogene Proteins / Q000097:blood*; D011897:Random Allocation; D012216:Rheumatic Diseases / Q000378:metabolism; D018805:Sepsis / Q000097:blood* / Q000503:physiopathology; D057170:Translational Research, Biomedical
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D015850:Interleukin-6; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008070:Lipopolysaccharides; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C071332:Lcn2 protein, mouse; D016753:Interleukin-10