Kidney Week

Abstract: TH-OR03

Prevention of Ischemia-Reperfusion Injury (IRI)-Induced AKI by Maintaining Na+/K+ ATPase Activity

Session Information

• AKI Mechanisms: Cellular and Organ Cross-Talk
  November 02, 2023 | Location: Room 118, Pennsylvania Convention Center
  Abstract Time: 04:48 PM - 04:57 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Zheleznova, Nadezhda N., University of South Florida, Tampa, Florida, United States

Nadezhda N. Zheleznova, PhD

• Wahbeh, Tamara Ayman, University of South Florida, Tampa, Florida, United States

Tamara Ayman Wahbeh,

• Wang, Lei, University of South Florida, Tampa, Florida, United States

Lei Wang,

• Zhang, Jie, Boston University, Boston, Massachusetts, United States

Jie Zhang,

• Wei, Jin, Boston University, Boston, Massachusetts, United States

Jin Wei,

• Hall, Nathan, University of South Florida, Tampa, Florida, United States

Nathan Hall,

• Hernandez Soto, Nohely, University of South Florida, Tampa, Florida, United States

Nohely Hernandez Soto,

• Chen, Bo, University of South Florida, Tampa, Florida, United States

Bo Chen,

• Chen, Wei, University of South Florida, Tampa, Florida, United States

Wei Chen,

• Liu, Ruisheng, University of South Florida, Tampa, Florida, United States

Ruisheng Liu,

Background

IRI impairs Na/K ATPase pump function leading to cellular death. We developed a method using a 3rd Generation Synchronization Modulation Electric field (SMEF) to optimize Na/K ATPase activity during ischemia (Sci Trans Med. 2022). Now, advanced to a 4^th Generation SMEF, we have incorporated dual-energy transformation functions and power injections for ATP generation, hypothesizing that it will more efficiently combat ischemia-reperfusion-induced acute kidney injury (AKI).

Methods

Male and female C57BL/6J mice were divided into 3 groups: sham control, AKI without 4th-SMEF, and AKI with 4th-SMEF. A right nephrectomy was performed, followed by warm ischemia induction by clamping of the left renal pedicle (20 min in males vs. 25 min in females). In the 4th-SMEF group, an electric field was applied to the left kidney pre-clamping. Plasma creatinine (Day 1,3,7), Glomerular Filtration Rate (day 7), KIM-1, and Na/K pump activity and expression were evaluated. A histological kidney tissue examination was conducted.

Results

The 4th-SMEF reduced plasma creatinine by 92% in males (4th-SMEF:0.21±0.10 mg/dL, untreated AKI:2.56±0.9 mg/dL) and 82% in females (4th-SMEF:0.34±0.3 mg/dL, untreated AKI 1.84±0.4 mg/dL), displaying similitude to sham groups. This outperforms the previous 3rd-SMEF approach, decreasing plasma creatinine by only 40% (Chen, 2022). GFR showed 60% improvement in males (4th-SMEF:255 μl/min, untreated AKI:110 μl/min) and 55% improvement in females (4th-SMEF: 220μl/min, untreated AKI:98μl/min). KIM-1 marker in the AKI-treated group, the sham, and 4th-SMEF-treated groups showed: (271±30 pg/ml, 60±9 pg/ml, and 66±21 pg/ml) respectively. Baseline Na/K expression is higher in females. AKI groups of both genders exhibited reduced activity, and expression, alongside cellular relocation. With 4th-SMEF, both genders reached equalized Na/K pump activity and degradation reduction. Histology conveyed diffuse renal tubular necrosis and casts comprising necrotic cells and debris in AKI groups. In contrast, the 4^th-SMEF treatment essentially normalized the histopathologic changes aiding strong similarity to the sham group.

Conclusion

4th-SMEF prevented AKI by equally normalizing Na/K pump activity in both genders of mice, leading to similar prevention of IRI-induced AKI.

Funding

• NIDDK Support