Abstract: SA-PO1186
Targeted Pulsed Ultrasound of the Spleen Protects against AKI and CKD and Permits Kidney Regeneration
Session Information
- CKD: Mechanisms - 3
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Goggins, Eibhlin S., Division of Nephrology, Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, United States
- Xie, Yanjun, University of Virginia Department of Biomedical Engineering, Charlottesville, Virginia, United States
- Huang, Yi, University of Virginia Department of Biomedical Engineering, Charlottesville, Virginia, United States
- Brantley, Carson Anderson, Division of Nephrology, Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, United States
- Yao, Junlan, Division of Nephrology, Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, United States
- Nash, William, Division of Nephrology, Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, United States
- Cechova, Sylvia, Division of Nephrology, Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, United States
- Hossack, John, University of Virginia Department of Biomedical Engineering, Charlottesville, Virginia, United States
- Okusa, Mark D., Division of Nephrology, Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, United States
Background
Our group has demonstrated that unfocused pulsed ultrasound (pUS) protects against ischemic AKI. The efficacy of pUS targeted directly to the mouse spleen and in kidney injury caused by other insults is unknown. Here, we aimed to 1) Develop an effective and reproducible pUS protocol specifically targeting the mouse spleen to block inflammation and prevent ischemia induced AKI 2) To test the hypothesis that pUS can prevent toxin induced AKI and the transition to CKD and that 3) pUS permits regeneration in the kidney microenvironment.
Methods
The US configuration consists of a power amplifier and waveform generator paired with a 1 MHz single element transducer with a stand-off of 1mm. The optimized stimulation parameters used were tonebursts of 150 cycles, pulse repetition frequency of 2kHz, and a peak-negative pressure of 280kPA. 4 min of pUS was delivered to the spleen 24h prior to folic acid (FA, 250mg/kg IP), lipopolysaccharide (LPS, 3.5mg/kg IP), or bilateral kidney ischemia reperfusion injury (bIRI, 25min).
Results
Mice that received spleen targeted pUS demonstrated significantly reduced plasma TNFα 1h after LPS. The increase in plasma creatinine (Cr) and BUN 24h after bIRI was significantly reduced in splenic pUS mice. In the FA model, the increase in Cr (Sham: 1.14±0.25, pUS: 0.32±0.04 mg/dL) and BUN (Sham: 155.8±23.2, pUS: 45.9±4.6 mg/dL) on day 2 was reduced in pUS mice. Analysis of H&E and PAS stained kidney sections demonstrated reduced injury in pUS treated mice. 23% of sham treated mice died over the 14d study period. On day 14, kidney mRNA levels of the fibrotic markers, Col1α1, Col3α1, and Fn-1 and proinflammatory cytokines, IL-1β, IL-6, and Ccl2 were decreased in pUS treated mice. pUS mice displayed reduced kidney tubulointerstitial fibrosis and collagen deposition by blinded assessment of Masson trichrome sections. Kidney mRNA expression of Wnt2, Wnt4 and the acute epithelial stress response gene, Sox9 remained persistently elevated in sham treated mice compared to pUS mice.
Conclusion
We developed a spleen targeted pUS protocol that reduces inflammation and prevents AKI/CKD in multiple mouse models. Future work is focused on understanding the mechanism by which pUS may promote a microenvironment conducive to kidney regeneration.
Funding
- Other NIH Support