Abstract: TH-PO0136
Mechanisms of Injury and Protection in Ischemic AKI
Session Information
- AKI: Mechanisms - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Campbell, Jillian R., Richard L Roudebush VA Medical Center, Indianapolis, Indiana, United States
- Dominguez, Jesus H., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Kelly, Katherine J., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background
Acute kidney injury (AKI) is frequent and deadly. Effective therapy is an unmet need. In experimental ischemia, we found that extracellular vesicles (EV, exosomes, nanovesicles released by most cells that serve in cell-cell communication), given non-invasively after renal failure is present, improve kidney function and structure.
Methods
Using spatial transcriptomics in an established model, we further examined the mechanisms of ischemic injury and protection with renal EV.
Results
We found that renal EV (in contrast to EV from platelets or skin epithelia) improved multiple injurious pathways postischemia; ~68% of transcripts altered with ischemia improved with renal EV. Macrophage markers were diffusely expressed postischemia, especially in the outer medulla adjacent to S3 proximal tubule segments, and decreased with renal, but not platelet or skin, EV. Staining for CD68 showed that protein expression was consistent with transcriptomic results. Lymphocyte markers showed a similar pattern. Elevations in complement components, chemokine and cytokine transcripts were also significantly improved with renal EV. Decreased inflammation was found in 28 day samples, consistent with a beneficial impact of renal EV on AKI-to-chronic kidney disease transition.
Conclusion
Ischemic renal injury is increasingly recognized as a major global health issue. Postischemic inflammation is a prominent mechanism of renal dysfunction. We have advocated for a multifaceted approach to renal injury, given the complex and intertwined pathophysiology. Renal EV can overcome the multiple pro-inflammatory changes seen postischemia. We also found that renal EV improve longer term consequence of ischemic AKI. EV, used here as "proof-of-principle," are an attractive therapeutic that have reached clinical trials in other conditions.
In spatial transcriptomic data, macrophage markers are widely expressed and remain elevated for 28 days postischemia (ISCH) and improve to sham levels with renal, but not platelet, EV. Staining for CD68 (green, nuclei in blue) shows that protein expression is consistent with spatial transcriptomic data.
Funding
- Other NIH Support