title: The pathogenesis of nephropathia epidemica: new knowledge and unanswered questions.
abstract: Puumala virus (PUUV) causes an acute hemorrhagic fever with renal syndrome (HFRS), a zoonosis also called nephropathia epidemica (NE). The reservoir host of PUUV is the bank vole (Myodes glareolus). Herein we review the main clinical manifestations of NE, acute kidney injury, increased vascular permeability, coagulation abnormalities as well as pulmonary, cardiac, central nervous system and ocular manifestations of the disease. Several biomarkers of disease severity have recently been discovered: interleukin-6, pentraxin-3, C-reactive protein, indoleamine 2,3-dioxygenase, cell-free DNA, soluble urokinase-type plasminogen activator, GATA-3 and Mac-2 binding protein. The role of cytokines, vascular endothelial growth hormone, complement, bradykinin, cellular immune response and other mechanisms in the pathogenesis of NE as well as host genetic factors will be discussed. Finally therapeutic aspects and directions for further research will be handled.
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland; Department of Internal Medicine, Tampere University Hospital, Tampere, Finland. Electronic address: jukka.mustonen@uta.fi.
authors.forename: Jukka
authors.initials: J
authors.lastname: Mustonen
authors.forename: Satu
authors.initials: S
authors.lastname: Mäkelä
authors.forename: Tuula
authors.initials: T
authors.lastname: Outinen
authors.forename: Outi
authors.initials: O
authors.lastname: Laine
authors.forename: Juulia
authors.initials: J
authors.lastname: Jylhävä
authors.forename: Petteri T
authors.initials: PT
authors.lastname: Arstila
authors.forename: Mikko
authors.initials: M
authors.lastname: Hurme
authors.forename: Antti
authors.initials: A
authors.lastname: Vaheri
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers; D001778:Blood Coagulation Disorders / Q000209:etiology; D001920:Bradykinin / Q000502:physiology; D002199:Capillary Permeability; D003131:Combined Modality Therapy; D003165:Complement System Proteins / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D004197:Disease Reservoirs / Q000821:virology; D005060:Europe / Q000453:epidemiology; D005387:Finland / Q000453:epidemiology; D005544:Forecasting; D006480:Hemorrhagic Fever with Renal Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000276:immunology / Q000628:therapy / Q000635:transmission / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007668:Kidney / Q000473:pathology; D029262:Puumala virus / Q000502:physiology; D006435:Renal Dialysis; D012377:Rodentia / Q000821:virology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016207:Cytokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003165:Complement System Proteins; D001920:Bradykinin
keywords: Hantavirus; Hemorrhagic fever with renal syndrome; Nephropathia epidemica; Puumala virus