Abstract: TH-PO0135
Mechanisms of Injury and Protection in Remote Organs After Kidney Ischemia
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
The cause of mortality in acute kidney injury (AKI) is often dysfunction of extra-renal organs, a possible reason for the lack of effective AKI therapy. We and others have found remote organ dysfunction and systemic inflammation after renal ischemia. We have also shown benefit with extracellular vesicles (EV, exosomes) given after renal injury.
Methods
Using spatial transcriptomics in an established renal ischemia model, we examined mechanisms of cardiac injury in AKI and the effects of a potential therapy (renal EV).
Results
Consistent with decreased left ventricular (LV) function seen after renal ischemia, LV atrial natriuretic peptide (ANP) transcripts were markedly upregulated 48 h after renal injury and improved with EV given after renal failure was present. Cardiac collagen increased and smooth muscle markers decreased with renal ischemia and were preserved in the presence of EV. Changes in smooth muscle actin are consistent with previously shown abnormal microvascular flow in multiple organs postischemia. In pathway analysis, cytoskeleton in muscle cells, actin regulation and cardiomyopathy pathways were among the most significantly altered with renal ischemia and improved with EV.
Conclusion
AKI is a major clinical challenge with adverse outcomes most commonly related to remote organ dysfunction and failure. Here we show that transcriptional changes impacting cardiac function occur after renal ischemia. Understanding the linkage of renal injury with remote organ effects is important in developing effective treatments to decrease AKI morbidity and mortality.
Cardiac spatial transcriptomic data show significant alterations in ANP, consistent with decreased function found after renal ischemia. By 48 hours postischemia, increased collagen transcripts are found. Both changes improved with EV given postischemia.
Funding
- Veterans Affairs Support