title: Acute ischemic injury to the renal microvasculature in human kidney transplantation.
abstract: Increased understanding of the pathophysiology of ischemic acute kidney injury in renal transplantation may lead to novel therapies that improve early graft function. Therefore, we studied the renal microcirculation in ischemically injured kidneys from donors after cardiac death (DCD) and in living donor kidneys with minimal ischemia. During transplant surgery, peritubular capillaries were visualized by sidestream darkfield imaging. Despite a profound reduction in creatinine clearance, total renovascular resistance of DCD kidneys was similar to that of living donor kidneys. In contrast, renal microvascular perfusion in the early reperfusion period was 42% lower in DCD kidneys compared with living donor kidneys, which was accounted for by smaller blood vessel diameters in DCD kidneys. Furthermore, DCD kidneys were characterized by smaller red blood cell exclusion zones in peritubular capillaries and by greater production of syndecan-1 and heparan sulfate (main constituents of the endothelial glycocalyx) compared with living donor kidneys, providing strong evidence for glycocalyx degradation in these kidneys. We conclude that renal ischemia and reperfusion is associated with reduced capillary blood flow and loss of glycocalyx integrity. These findings form the basis for development of novel interventions to prevent ischemic acute kidney injury.
authors.affiliation: Dept. of Surgery, Maastricht Univ. Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands. m.snoeijs@mumc.nl
authors.forename: Maarten G
authors.initials: MG
authors.lastname: Snoeijs
authors.forename: Hans
authors.initials: H
authors.lastname: Vink
authors.forename: Niek
authors.initials: N
authors.lastname: Voesten
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Christiaans
authors.forename: Jan-Willem H
authors.initials: JW
authors.lastname: Daemen
authors.forename: Arnoud G
authors.initials: AG
authors.lastname: Peppelenbosch
authors.forename: Jan H
authors.initials: JH
authors.lastname: Tordoir
authors.forename: Carine J
authors.initials: CJ
authors.lastname: Peutz-Kootstra
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.forename: Geert Willem H
authors.initials: GW
authors.lastname: Schurink
authors.forename: L W Ernest
authors.initials: LW
authors.lastname: van Heurn
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D002196:Capillaries / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D019276:Glycocalyx / Q000473:pathology; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000473:pathology*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000502:physiology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D012079:Renal Circulation / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology; D053668:Syndecan-1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D006497:Heparan Sulfate; D019007:P-Selectin; D053668:Syndecan-1