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Kidney Week

Abstract: FR-PO118

Mechanisms of Protection From Ischemic Injury With Renal Exosomes

Session Information

  • AKI: Mechanisms - II
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Kelly, Katherine J., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Dominguez, Jesus H., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Ischemic renal injury results in tremendous acute and chronic morbidity and mortality and has no specific therapy. We have demonstrated marked improvement in postischemic kidney function and structure with exosomes (EV) from tubular cells given after renal failure was established. EV from skin epithelia or platelets were not effective, allowing the examination of the mechanisms of benefit with renal EV.

Methods

In a well established model of renal ischemia/reperfusion injury, EV or vehicle was given 24 hours after ischemia when renal failure was established. A model of anoxia/reoxygenation injury in primary renal tubular cells was used and apoptosis, inflammatory mediators, leukocyte adhesion and oxidative stress quantified in cells treated with vehicle or EV from different sources. Apoptotic cell death was quantified by TUNEL; leukocytes were fluorescently labeled to measure adhesion; expression of the inflammatory mediators C3, C5 and ICAM1 was evaluated by immunohistochemistry; generation of reactive oxygen species (ROS) was measured using dichlorodihydrofluorescein diacetate; and bax, superoxide dismutase and catalase expression analyzed by immunoblot.

Results

Renal EV, but not those derived from skin or platelets, significantly decreased anoxic renal cell death. A major effect of renal EV was anti-inflammatory (table). Leukocyte adhesion and expression of complement components C3 and C4 and intracellular adhesion molecule 1 were all significantly improved in the presence of renal EV as compared to either skin or platelet EV.

Conclusion

The benefits of renal exosomes in ischemic injury are multifacited and include decreasing multiple pro-inflammatory mediators.

MEDIATORS OF INJURY (fold change vs normoxia)
 TUNEL+WBC adhesionICAMC3C5SODCATROSbax
vehicle/anoxia8.8
51.57.96.48.90.190.652.79.7
renal EV/anoxia2.0*8.5*2.5*2.0*1.5*0.89*2.5*0.5*3.8*
skin EV/anoxia7.643.06.8*5.2*4.5*0.251.00.97.4
platelet EV/anoxia7.240.56.7*5.0*4.4*0.261.10.98.0

*p<0.01 vs vehicle/anoxia

Funding

  • Other NIH Support