title: Carbamylated erythropoietin-FC fusion protein and recombinant human erythropoietin during porcine kidney ischemia/reperfusion injury.
abstract: OBJECTIVE
  To test the hypothesis that a carbamylated EPO-FC fusion protein (cEPO-FC) or recombinant human erythropoietin (rhEPO) would protect against kidney ischemia/reperfusion (I/R) injury in pigs with atherosclerosis.
  
  
  METHODS
  Anesthetized and mechanically ventilated animals received cEPO-FC (50 μg kg(-1)), rhEPO (5,000 IU kg(-1)), or vehicle (n = 9 per group) prior to 120 min of aortic occlusion and over 4 h of reperfusion. During aortic occlusion, mean arterial pressure (MAP) was maintained at 80-120 % of baseline values by esmolol, nitroglycerin, and ATP. During reperfusion, noradrenaline was titrated to keep MAP at pre-ischemic levels. Blood creatinine and neutrophil gelatinase-associated lipocalin (NGAL) levels, creatinine clearance, fractional Na(+) excretion, and HE and PAS staining were used to assess kidney function and histological damage. Plasma interleukin-6, tumor necrosis factor-α, nitrate + nitrite and 8-isoprostane levels were measured to assess systemic inflammation, and nitrosative and oxidative stress.
  
  
  RESULTS
  I/R caused acute kidney injury with reduced creatinine clearance, increased fractional Na(+) excretion and NGAL levels, moderate to severe glomerular and tubular damage and apoptosis, systemic inflammation and oxidative and nitrosative stress, but there were no differences between the treatment groups. Pre-ischemia nitrate + nitrite and 8-isoprostanes levels were lower and higher, respectively, than in healthy animals of a previous study, and immune histochemistry showed higher endothelial nitric oxide synthase and lower EPO receptor expression in pre-ischemia kidney biopsies than in biopsies from healthy animals.
  
  
  CONCLUSIONS
  In swine with atherosclerosis, rhEPO and cEPO-FC failed to attenuate prolonged ischemia-induced kidney injury within an 8-h reperfusion period, possibly due to reduced EPO receptor expression resulting from pre-existing oxidative stress and/or reduced NO release.
authors.affiliation: Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Klinik für Anästhesiologie, Universitätsklinikum, Helmholtzstrasse 8-1, 89081 Ulm, Germany. sarka_matejkova@web.de
authors.forename: Šárka
authors.initials: Š
authors.lastname: Matějková
authors.forename: Angelika
authors.initials: A
authors.lastname: Scheuerle
authors.forename: Florian
authors.initials: F
authors.lastname: Wagner
authors.forename: Oscar
authors.initials: O
authors.lastname: McCook
authors.forename: José
authors.initials: J
authors.lastname: Matallo
authors.forename: Michael
authors.initials: M
authors.lastname: Gröger
authors.forename: Andrea
authors.initials: A
authors.lastname: Seifritz
authors.forename: Bettina
authors.initials: B
authors.lastname: Stahl
authors.forename: Brigitta
authors.initials: B
authors.lastname: Vcelar
authors.forename: Enrico
authors.initials: E
authors.lastname: Calzia
authors.forename: Michael
authors.initials: M
authors.lastname: Georgieff
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Hubert
authors.initials: H
authors.lastname: Schelzig
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Florian
authors.initials: F
authors.lastname: Simon
mesh_terms: D000818:Animals; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine
chemical_list: D007074:Immunoglobulin G; D011994:Recombinant Proteins; C488171:carbamylated erythropoietin; D004921:Erythropoietin