title: Ex vivo use of a Rho-kinase inhibitor during renal preservation improves graft function upon reperfusion.
abstract: BACKGROUND
  Activation of the Rho-Rho-kinase pathway has been shown to cause vasoconstriction in renal afferent arterioles. Vascular dysfunction plays a pivotal role in triggering reperfusion injury after kidney transplantation. Therefore, the effect of a Rho-kinase inhibitor, added to the preservation solution, on renal function after 18 h of storage at 4 °C was evaluated.
  
  
  METHODS
  Porcine kidneys were preserved with cold HTK-solution. During preservation, in the study group, HTK was supplemented with the Rho-kinase inhibitor HA1077, whereas the control group received no further treatment (n=6, respectively). Kidney function after 18 h of storage at 4 °C was evaluated by 90 min of isolated reperfusion in vitro.
  
  
  RESULTS
  Rho-kinase inhibition (RKI) was associated with significantly higher renal perfusate flow compared to the control group. Endothelial function, as measured by perfusate levels of nitric oxide and gene expression of eNOS, was significantly increased in the study group. In our model, RKI also significantly improved glomerular function (clearance of creatinine) as well as tubular cell integrity as reflected by reduced fractional sodium excretion and release of fatty acid binding protein, a specific tubular cell marker.
  
  
  CONCLUSIONS
  Our results indicate that blocking the Rho-kinase pathway during cold preservation may lead to a better graft function upon reperfusion.
authors.affiliation: Clinic of General, Visceral and Transplantation Surgery, University Hospital of Essen, Germany. Electronic address: Carmen.Kirchner@uk-essen.de.
authors.forename: Carmen
authors.initials: C
authors.lastname: Kirchner
authors.affiliation: Surgical Research Division, University Clinic of Surgery, Bonn, Germany. Electronic address: b.l.1982@gmx.de.
authors.forename: Bastian
authors.initials: B
authors.lastname: Lüer
authors.affiliation: Surgical Research Division, University Clinic of Surgery, Bonn, Germany. Electronic address: Patrik.Efferz@ukb.uni-bonn.de.
authors.forename: Patrik
authors.initials: P
authors.lastname: Efferz
authors.affiliation: Dpt. for Pathology, University Hospital of Essen, Germany. Electronic address: Jeremias.wohlschlaeger@uk-essen.de.
authors.forename: Jeremias
authors.initials: J
authors.lastname: Wohlschlaeger
authors.affiliation: Clinic of General, Visceral and Transplantation Surgery, University Hospital of Essen, Germany. Electronic address: Andreas.Paul@uk-essen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Paul
authors.affiliation: Surgical Research Division, University Clinic of Surgery, Bonn, Germany. Electronic address: minor@uni-bonn.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Minor
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003404:Creatinine / Q000378:metabolism; D015925:Cryopreservation / Q000379:methods; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects*; D007668:Kidney / Q000201:enzymology / Q000502:physiology*; D016030:Kidney Transplantation; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D009926:Organ Preservation / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015424:Reperfusion; D015427:Reperfusion Injury / Q000473:pathology; D013552:Swine; D014661:Vasoconstriction / Q000502:physiology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D009569:Nitric Oxide; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003404:Creatinine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D054460:rho-Associated Kinases; C049347:fasudil
keywords: Kidney perfusion; Preservation; Renovasculature; Rho-kinase