Kidney Week

Abstract: SA-PO0177

Vitamin B12 Attenuates CKD Progression Exacerbated by ELMO1 Overexpression in Ischemia-Reperfusion Injury

Session Information

• AKI: Mechanisms - 3
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Zhou, Jiayi, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States

Jiayi Zhou, RD, RDN, MPH

• Li, Feng, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States

Feng Li, PhD

• Maeda, Nobuyo, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States

Nobuyo Maeda, PhD

Background

Kidney ischemia-reperfusion (IR) injury is a leading cause of acute kidney injury and a major driver of chronic kidney disease. Clinically, AKI affects up to 20% of hospitalized patients and increases the risk of long-term renal decline. IR-induced oxidative stress, inflammation, mitochondrial dysfunction, and endothelial injury impair recovery and promote fibrosis. Engulfment and Cell Motility 1 (ELMO1) regulates apoptotic cell clearance and immune signaling, and genetic variants in ELMO1 are linked to kidney disease. While ELMO1 modulates oxidative stress in other conditions, its role in AKI-to-CKD progression remains unclear. We hypothesized that ELMO1 overexpression worsens IR-induced injury through enhanced ROS production and that vitamin B12—a potent antioxidant—could mitigate these effects.

Methods

Wild-type (WT) and Elmo1^H/H mice underwent unilateral renal IR surgery and received either water or vitamin B12 (50 mg/L) in drinking water for 4 months. Kidney function was assessed by plasma cystatin C and urinary albumin-to-creatinine ratio (UACR). Renal structures were examined by light and electron microscopy. Oxidative stress markers were analyzed by western blot and qRT-PCR. Statistical analysis was performed using JMP Pro (v17.2).

Results

Elmo1^H/H mice showed significantly worsened kidney function at 4 months post-IR, with elevated cystatin C and UACR compared to WT. Histology revealed increased tubular damage and interstitial fibrosis. Electron microscopy showed podocyte foot process effacement, loss of filtration slits, endothelial fenestration loss, and mitochondrial swelling. Antioxidant genes (Sod1, Gpx1) were reduced, and Nox2 was elevated in Elmo1^H/H kidneys. Vitamin B12 treatment improved kidney function and structure and restored antioxidant gene expression in both genotypes.

Conclusion

ELMO1 overexpression exacerbates oxidative stress and worsens IR-induced CKD. Vitamin B12 treatment alleviates these effects, supporting its potential as a safe, accessible therapy to reduce oxidative damage and slow CKD progression after AKI.

Funding

• Other NIH Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025dsp7f4q1