Acute ischemic injury to the renal microvasculature in human kidney transplantation

Area of Science:

• Nephrology
• Transplantation immunology
• Vascular biology

Background:

• Ischemic acute kidney injury (AKI) is a major complication in renal transplantation.
• Understanding the pathophysiology of AKI in DCD (donors after cardiac death) kidneys is crucial for improving graft function.
• The renal microcirculation's role in early graft dysfunction requires further investigation.

Purpose of the Study:

• To investigate the renal microcirculation in DCD kidneys compared to living donor kidneys with minimal ischemia.
• To identify factors contributing to reduced graft function following transplantation.
• To explore the integrity of the endothelial glycocalyx in DCD kidneys.

Main Methods:

• Sidestream darkfield imaging was used to visualize peritubular capillaries during transplant surgery.
• Renal microvascular perfusion, renovascular resistance, and blood vessel diameters were assessed.
• Red blood cell exclusion zones and the production of syndecan-1 and heparan sulfate were analyzed.

Main Results:

• DCD kidneys exhibited 42% lower renal microvascular perfusion compared to living donor kidneys.
• Smaller blood vessel diameters in DCD kidneys accounted for reduced perfusion.
• Evidence of endothelial glycocalyx degradation was observed in DCD kidneys, indicated by smaller exclusion zones and increased syndecan-1 and heparan sulfate production.

Conclusions:

• Renal ischemia and reperfusion injury in DCD kidneys is associated with compromised capillary blood flow.
• Loss of endothelial glycocalyx integrity contributes to impaired microcirculation.
• These findings provide a basis for developing novel interventions to prevent ischemic AKI in renal transplantation.