title: Erythropoietin administration is associated with short-term improvement in glomerular filtration rate after ischemia-reperfusion injury.
abstract: BACKGROUND
  Erythropoietin (EPO) is a cytokine with organ-protective properties. We hypothesized that EPO could attenuate acute renal dysfunction and inflammation in a porcine model of ischemia-reperfusion (IR). Furthermore, we aimed to characterize the impact of EPO on systemic and renal hemodynamics, and renal oxygen consumption.
  
  
  METHODS
  Twenty-four pigs were randomly assigned to three groups: (1) EPO (5000 IU/kg) administered intravenously before IR (n=9), (2) placebo administered before IR (n=9), or (3) sham group, anesthetized and operated on only (n=6). IR was induced by clamping the left renal artery for 45 min. Hemodynamics and renal blood flow (RBF) were analyzed continuously. Glomerular filtration rate (GFR), renal oxygen consumption, and plasma cytokines (IL-1β, IL-6, IL-8, IL-10, and TNF-α) were analyzed hourly. Renal biopsies were analyzed for cytokine content and apoptosis.
  
  
  RESULTS
  GFR was higher during reperfusion in the EPO group than in the placebo group (P<0.01). No differences between the IR groups were found in hemodynamics, RBF, oxygen consumption, or renal apoptosis. The levels of TNF-α in the plasma (P=0.036) and the levels of TNF-α and IL-10 in the renal cortex (P=0.04 and P=0.01, respectively) were lower in the EPO group compared with the sham group.
  
  
  CONCLUSIONS
  EPO attenuated the renal dysfunction as estimated as GFR. This effect was not related to changes in the hemodynamics. The immunomodulatory effects of EPO were manifested as decreased levels of TNF-α and IL-10 in renal biopsies and TNF-α levels in plasma.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Denmark. solling@ki.au.dk
authors.forename: C
authors.initials: C
authors.lastname: Sølling
authors.forename: A T
authors.initials: AT
authors.lastname: Christensen
authors.forename: S
authors.initials: S
authors.lastname: Krag
authors.forename: J
authors.initials: J
authors.lastname: Frøkiaer
authors.forename: L
authors.initials: L
authors.lastname: Wogensen
authors.forename: J
authors.initials: J
authors.lastname: Krog
authors.forename: E K
authors.initials: EK
authors.lastname: Tønnesen
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004921:Erythropoietin / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000502:physiology; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007677:Kidney Function Tests; D010101:Oxygen Consumption / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology*; D013552:Swine
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; D004921:Erythropoietin; D053148:Caspase 3