Abstract: TH-PO099
Distant Organ Effects of Renal Injury
Session Information
- AKI: Mechanisms - I
November 03, 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
Acute kidney injury (AKI) results in immense human and economic cost. The cause of death in AKI is often not kidney failure per se. An enlarging body of data supports the systemic harmful effects of AKI. Understanding the linkage of renal injury with distant organ effects is critical in evaluating potential therapies and preventing/reducing morbidity and mortality.
Methods
We employed a well characterized model of renal ischemia/reperfusion injury to examine the effect on distant organs (heart, dura, small intestine, mesentery, liver and spleen) both short term (48 h) and longer term (10 wk) after renal injury. We have previously shown the beneficial effect of renal exosomes, given after renal failure is established, on the kidney. In the present work, we examine the effect of this potential therapy systemically. Controls included sham surgery, unilateral ischemia and nephrectomy (48 hours only).
Results
We found leukocyte infiltration following renal ischemia in the heart, dura, small intestine, mesentery, liver and spleen, 2-5 fold the levels following nephrectomy. Tumor necrosis factor alpha was significantly increased in heart, lung and spleen 48 hours after renal ischemia, 2-90 fold. In the heart, significantly altered transcripts included inflammatory (C3, C4), fibrotic (collagen 1, 5, TIMP), angiogenic (VEGF), oxidant (superoxide dismutase, catalase) and apoptosis (bak, bcl2) related, examples in table. Although renal exosomes were not found in large numbers in remote organs, leukocyte infiltration was significantly decreased in these organs in the exosome-treated postischemia group. In longer term studies, we found increased heart and liver weights (1.7 and 1.2 fold increased vs sham surgery, respectively, p<0.03), which was ameliorated (1.2 and 1.0 fold, p<0.04) after treatment with renal exosomes. More importantly, longer term mortality in the post-renal ischemia group (50%) was eliminated (0%) in the exosome treated group, p<0.04.
Conclusion
Significant remote organ alterations after found after renal ischemia and these can be improved with exosome treatment after renal failure is established.
CARDIAC TRANSCRIPTS (fold change renal ischemia vs sham, examples)
| C4 | 1.75 |
| TIMP | 0.65 |
| SOD | 0.63 |
| VEGF | 0.75 |
| Bcl2 | 1.22 |
Funding
- Other NIH Support