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bioRxiv · 10.64898/2026.10.15.759393

Modified 3rd Generation Synchronization Modulation Electric Field (3m-SMEF) Prevents Ischemia-Reperfusion-Induced Acute Kidney Injury via Targeting Na⁺/K⁺-ATPase

Hall, N.·Zeleznova, N. N.·Esquivel, C.·Wahbeh, T.·Parris, C.·Lozonschi, I.·Hernandez, N.·Wang, L.·Chen, W.·Liu, R.
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Abstract

Acute kidney injury (AKI) caused by ischemia-reperfusion injury (IRI) remains a major clinical problem with limited therapeutic options. We previously demonstrated that the 3rd-generation Synchronization Modulation Electric Field (SMEF) preserves Na/K-ATPase function during ischemia and protects against kidney injury. In the present study, we substantially modified the 3rd-generation SMEF (3m-SMEF) to further improve/optimize Na/K-ATPase regulation and enhance the protective effects, which was tested both in vitro and in vivo. In HK-2 cells, hypoxia/reoxygenation reduced Na/K-ATPase expression and induced apoptotic and necroptotic signaling, whereas 3m-SMEF restored Na/K-ATPase expression and markedly reduced cell death. In vivo, male and female mice underwent unilateral renal ischemia with or without 3m-SMEF treatment during vascular clamping. At 24 h, 3m-SMEF markedly improved renal function, reducing plasma creatinine by ~90-95% and restoring glomerular filtration rate to near-control levels. Application of the 3m-SMEF also normalized kidney injury markers (KIM-1 and NGAL), preserved renal ATP, and prevented the translocation and loss of Na/K-ATPase expression. The renoprotective effects substantially exceeded those achieved with the previous SMEF platform. These findings demonstrate that 3m-SMEF provides robust protection against ischemic AKI by preserving Na/K-ATPase function and tubular integrity and represents a promising non-pharmacological therapy for ischemic kidney injury.

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Hall, N., Zeleznova, N. N., Esquivel, C., Wahbeh, T., Parris, C., Lozonschi, I., Hernandez, N., Wang, L., Chen, W., Liu, R.. 2026-10-21. Modified 3rd Generation Synchronization Modulation Electric Field (3m-SMEF) Prevents Ischemia-Reperfusion-Induced Acute Kidney Injury via Targeting Na⁺/K⁺-ATPase. https://doi.org/10.64898/2026.10.15.759393

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