---
title: "3m-SMEF Protects Against Ischemia-Reperfusion Acute Kidney Injury by Preserving Na⁺/K⁺-ATPase"
id: "biorxiv-8-modified-3rd-generation-synchronization-modulation-electric-field-3m-smef"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-8-modified-3rd-generation-synchronization-modulation-electric-field-3m-smef"
content_type: "clinical_feed_article"
specialty: "Nephrology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.15.759393v1?rss=1"
published_at: "2026-10-21T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# 3m-SMEF Protects Against Ischemia-Reperfusion Acute Kidney Injury by Preserving Na⁺/K⁺-ATPase
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-8-modified-3rd-generation-synchronization-modulation-electric-field-3m-smef
- **Specialty:** [Nephrology](https://medichelpline.com/clinical-feed/nephrology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.15.759393v1?rss=1)
- **Published At:** 2026-10-21T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The preprint reports a modified third-generation Synchronization Modulation Electric Field (**3m-SMEF**) that targets and preserves **Na⁺/K⁺-ATPase** during ischemia-reperfusion injury (IRI). - In human proximal tubule HK-2 cells exposed to hypoxia/reoxygenation, investigators reported reduced Na⁺/K⁺-ATPase expression and activation of apoptotic and necroptotic signaling; application of **3m-SMEF** restored Na⁺/K⁺-ATPase expression and substantially reduced cell death. - In a murine unilateral renal ischemia model, the study team observed that **3m-SMEF** applied during vascular clamping markedly improved renal function at 24 hours, reducing plasma creatinine by approximately 90–95% and restoring glomerular filtration rate to near-control values. - Authors noted that **3m-SMEF** normalized kidney injury markers, including KIM-1 and NGAL, preserved renal ATP content, and prevented translocation and loss of Na⁺/K⁺-ATPase expression in injured kidneys. - The reported renoprotection with **3m-SMEF** exceeded effects seen with the prior SMEF platform, according to the authors; the preprint does not provide comparative quantitative details beyond the abstract. - The article is a bioRxiv preprint and has not undergone peer review; the source did not report detailed device parameters, stimulation dosing, long-term outcomes, or safety/tolerability data in the abstract. - Funders listed include multiple NIDDK R01 and R41 grants; authors declared no competing interests. Further peer-reviewed validation and reporting of stimulation parameters, sex-specific analyses, and longer-term functional endpoints remain unanswered by the preprint.
## Clinical Analysis & Structured Key Points
Modified 3rd Generation Synchronization Modulation Electric Field (3m-SMEF) Prevents Ischemia-Reperfusion-Induced Acute Kidney Injury via Targeting Na⁺/K⁺-ATPase | bioRxiv Skip to main content New Results Modified 3rd Generation Synchronization Modulation Electric Field (3m-SMEF) Prevents Ischemia-Reperfusion-Induced Acute Kidney Injury via Targeting Na⁺/K⁺-ATPase Nathan Hall , Nadezhda N Zeleznova , Carlos Esquivel , Tamara Wahbeh , Colby Parris , Isabella Lozonschi , Nohely Hernandez , Lei Wang , Wei Chen , Ruisheng Liu doi: https://doi.org/10.64898/2026.10.15.759393 Nathan Hall 1 University of South Florida; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Nadezhda N Zeleznova 1 University of South Florida; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Carlos Esquivel 1 University of South Florida; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Tamara Wahbeh 2 Banner Health Find this author on Google Scholar Find this author on PubMed Search for this author on this site Colby Parris 1 University of South Florida; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Isabella Lozonschi 1 University of South Florida; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Nohely Hernandez 1 University of South Florida; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Lei Wang 1 University of South Florida; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Wei Chen 1 University of South Florida; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ruisheng Liu 1 University of South Florida; Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: ruisheng{at}usf.edu Abstract Info/History Metrics Preview PDF 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. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared National Institute of Diabetes and Digestive and Kidney Disease of the National Institutes of Health , R01DK138092 , R01DK134000 , R01DK134028 , R41DK130764 , R42130764 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. 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Share Modified 3rd Generation Synchronization Modulation Electric Field (3m-SMEF) Prevents Ischemia-Reperfusion-Induced Acute Kidney Injury via Targeting Na⁺/K⁺-ATPase Nathan Hall , Nadezhda N Zeleznova , Carlos Esquivel , Tamara Wahbeh , Colby Parris , Isabella Lozonschi , Nohely Hernandez , Lei Wang , Wei Chen , Ruisheng Liu bioRxiv 2026.10.15.759393; doi: https://doi.org/10.64898/2026.10.15.759393 Share This Article: Copy Citation Tools Modified 3rd Generation Synchronization Modulation Electric Field (3m-SMEF) Prevents Ischemia-Reperfusion-Induced Acute Kidney Injury via Targeting Na⁺/K⁺-ATPase Nathan Hall , Nadezhda N Zeleznova , Carlos Esquivel , Tamara Wahbeh , Colby Parris , Isabella Lozonschi , Nohely Hernandez , Lei Wang , Wei Chen , Ruisheng Liu bioRxiv 2026.10.15.759393; doi: https://doi.org/10.64898/2026.10.15.759393 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8164) Animal Behavior and Cognition (8165) Animal Behavior and Cognition (8165) Animal Behavior and Cognition (8165) Animal Behavior and Cognition (8165) Animal Behavior and Cognition (8165) Animal Behavior and Cognition (8165) Animal Behavior and Cognition Animal Behavior and Cognition (8165) Animal Behavior and Cognition Animal Behavior and Cognition (8165) Animal Behavior and Cognition Animal Behavior and Cognition Animal Behavior and Cognition (8165) Biochemistry (19027) Biochemistry (19029) Biochemistry (19029) Biochemistry Biochemistry (19029) Biochemistry Biochemistry (19029) Biochemistry Biochemistry (19029) Biochemistry (19029) Biochemistry (19029) Biochemistry Biochemistry (19029) Biochemistry (19029) Biochemistry Biochemistry (19029) Biochemistry (19029) Biochemistry (19029) Biochemistry (19029) Biochemistry (19029) Biochemistry Biochemistry (19030) Biochemistry (19030) Biochemistry (19030) Biochemistry (19030) Biochemistry (19030) Bioengineering (15171) Bioengineering (15172) Bioengineering (15172) Bioengineering (15176) Bioengineering (15176) Bioengineering (15172) Bioengineering (15176) Bioinformatics (45258) Bioinformatics (45254) Bioinformatics Bioinformatics (45257) Biophysics (22958) Biophysics (22961) Biophysics Biophysics (22958) Biophysics (22958) Biophysics Biophysics (22958) Biophysics (22958) Biophysics (22961) Cancer Biology (20081) Cancer Biology (20080) Cell Biology (27277) Clinical Trials Clinical Trials (138) Clinical Trials (138) Developmental Biology (14134) Ecology (21378) Epidemiology (2067) Evolutionary Biology (25764) Genetics (16328) Genomics (23805) Immunology (19003) Microbiology (43137) Molecular Biology (18316) Neuroscience (94944) Paleontology (711) Pathology (3028) Pharmacology and Toxicology (5187) Physiology (8264) Plant Biology (16252) Scientific Communication and Education (2115) Synthetic Biology (4639) Systems Biology (10372) Zoology (2423)
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