Acute ischemic injury to the renal microvasculature in human kidney transplantation.
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.
Snoeijs
Maarten G
MG
Dept. of Surgery, Maastricht Univ. Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands. m.snoeijs@mumc.nl
Vink
Hans
H
Voesten
Niek
N
Christiaans
Maarten H
MH
Daemen
Jan-Willem H
JW
Peppelenbosch
Arnoud G
AG
Tordoir
Jan H
JH
Peutz-Kootstra
Carine J
CJ
Buurman
Wim A
WA
Schurink
Geert Willem H
GW
van Heurn
L W Ernest
LW
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
D006497:Heparan Sulfate; D019007:P-Selectin; D053668:Syndecan-1