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Kidney Week

Abstract: FR-PO121

Mechanisms of Remote Organ Dysfunction in AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Kelly, Katherine J., Indiana University, Indianapolis, Indiana, United States
  • Xie, Danhui, IUPUI, Indianapolis, Indiana, United States
  • Dominguez, Jesus H., Indiana University, Indianapolis, Indiana, United States
Background

While ~1.7 million acute kidney injury (AKI) patients die each year, the very high mortality rate is largely due to failure of extra-renal organs and not typically caused by renal dysfunction. We and others have shown persistent coagulation abnormalities and impaired renal microvascular function in experimental AKI. We hypothesize that the clotting abnormalities are systemic and contribute to multi-organ dysfunction in AKI.

Methods

The role of activated coagulation, microvascular dysfunction and impaired perfusion were assessed in a model of ischemic AKI using multiphoton, intravital imaging. The effects of a fibrinolytic agent were also examined.

Results

In addition to diffuse renal microvascular thrombi, we found heterogeneous clotting in the microvasculature of the brain, intestine, mesentery, liver, spleen and lung after renal ischemia. Microvascular flow was significantly decreased 48 hours after renal ischemia, to 24-58% of sham levels in different organs. In addition, tissue factor was increased postischemia in the kidney, heart, lung, liver and serum (2.4-4.2 fold, p<0.04). In the heart, expression of tissue factor pathway inhibitor was 0.54 +/- 0.1 fold that seen in shams (p<0.05). In addition, left ventricular function was impaired. Plasma flow and microvascular thrombi in remote organs improved with fibrinolytic therapy given after renal failure was established.

Conclusion

Our data indicate persistent systemic coagulation abnormalities after ischemic renal injury contributes to sustained, heterogeneous ischemia, leading to inflammation and tissue injury in multiple extra-renal organs. We have previously shown decreased cardiac function in experimental AKI. The systemic abnormalities likely contribute to the morbidity and mortality of AKI, but are amenable to therapeutic intervention.

representative intravital images

Funding

  • Veterans Affairs Support