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Kidney Week

Abstract: SA-PO175

Distant Organ Consequences of Renal Ischemia and the Effect of Renal Extracellular Vesicles (Exosomes)

Session Information

  • AKI: Mechanisms - III
    November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    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

Acute kidney injury is common, expensive and deadly. Morbidity and mortality remain very high; there is no specific treatment, yet the cause of death is frequently due to failure of extra-renal organs. We and others have demonstrated remote organ dysfunction and systemic inflammation following renal ischemia. We have also shown beneficial effects of extracellular vesicles (EV, exosomes) in models of renal injury. We hypothesized that EV would also decrease remote organ inflammation following renal ischemia. However, the effect of EV in the presence of renal failure could be limited.

Methods

The studies employed a well-characterized model of renal ischemia. Multiple time periods of ischemia were used in order to assess the effect of EV treatment independent of renal function. Both tissue and systemic inflammation as well as cell death were quantified.

Results

As in previous studies, markedly improved renal function and structure were found postischemia in groups treated with renal EV, given 24 hours after renal ischemia when renal failure had been established. Systemic inflammation, quantified as serum interleukin-1, -6 and tumor necrosis factor alpha, was significantly decreased in the treated group, even in the presence of prolonged ischemia. Tissue inflammation varied with the organ examined. The number of neutrophils in the heart decreased in the renal ischemia/EV group (figure 1). Anti-inflammatory interleukin-10 was significantly increased in all organs evaluated in the EV treated group, from 110-138% of sham levels. Evidence of apoptotic cell death was decreased in the heart in the EV treated groups.

Conclusion

Systemic and remote organ manifestations of inflammation after renal ischemia are amenable to treatment. Exosomes derived from renal tubule cells improve multiple abnormalities following renal ischemia.

Representative sections of esterase stained neutrophils in the heart following renal ischemia +/- exosomes

Funding

  • Other NIH Support