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Abstract: TH-PO121

No-Reflow in Experimental AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Dominguez, Jesus H., VAMC, Indianapolis, Indiana, United States
  • Xie, Danhui, Indiana University, Indianapolis, Indiana, United States
  • Dominguez, James M., Indiana University, Indianapolis, Indiana, United States
  • Kelly, Katherine J., Indiana University, Indianapolis, Indiana, United States

In acute kidney injury (AKI), multiple redundant pathways contribute to renal failure. Renal microvascular congestion has been observed in clinical AKI. We sought to test the hypothesis that inadequate reperfusion, activation of coagulation and microthrombi are significant factors that result in renal failure following ischemia. We have previously (Dominguez et al, J Am Soc Neph 28:3533) demonstrated improvement in multiple abnormal pathways of injury with exosome therapy.


The role of activated coagulation, microthrombi formation and fibrinolysis were examined in a model of ischemic AKI using multiphoton, intravital imaging performed 48 hours postischemia. Four groups of rats were studied: sham surgery, bilateral renal ischemia/reperfusion (IR)/vehicle, IR/exosomes, IR/urokinase. Exosomes derived from renal tubular epithelia, urokinase or vehicle (0.9% NaCl) was administered 24 hours postischemia when renal failure was established.


Diffuse renal microvascular thrombi resulted in a heterogeneous decrease in intrarenal blood flow within postischemic kidneys. Administration of exosomes after renal failure occurred, resulted in improved renal blood flow and decreased inflammation, fibrin formation and immunoreactive tissue factor. Urokinase, given after renal failure, improved intrarenal blood flow and decreased renal fibrin and tissue factor, but had less effect on inflammation. Renal function improved rapidly in both the exosome and urokinase groups.


Our data indicate that the no-reflow phenomenon follows global renal ischemia and contributes to heterogeneous, ongoing ischemia leading to a cycle of inflammation, tissue injury and postischemic renal failure. In this model, fibrinolysis improves renal function postischemia.

RENAL PARAMETERS 48 hours postischemia/24 hours post therapy (exosomes or urokinase)
Serum creatinine (mg/dl)Mean RBC velocity (um/sec)RBC velocity
sec (%)
RBC velocity
sec (%)
Microvascular diameter (um)PMN
Tissue factor (% area of staining)Fibrin(% area of staining)

*p<0.05 v ischemia/vehicle; #p<0.05 v ischemia/exosomes; PMN, polymorphonuclear neutrophil


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