Kidney Week

Abstract: FR-PO0147

Metabolic Imaging Differentiates Ischemia-Reperfusion Injury Severity in a Translational Mouse Model

Session Information

• AKI: Mechanisms - 2
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Zavriyev, Alexander I, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Alexander I Zavriyev

• Adebesin, Bukola Y, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Bukola Y Adebesin

• Nguyen, John, University of Pennsylvania, Philadelphia, Pennsylvania, United States

John Nguyen

• Boehmler, Daniel, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Daniel Boehmler

• Sheehan, Molly Marie, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Molly Marie Sheehan, PhD

• Wang, Zhonglin, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Zhonglin Wang, MD

• Yu, Jiangsheng, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Jiangsheng Yu, PhD

• Islam, Ariful, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Ariful Islam, MS

• Ge, Guanghui, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Guanghui Ge, MD

• Hartung, Erum Aftab, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Erum Aftab Hartung, MD, MS

• Levine, Matthew H., University of Pennsylvania, Philadelphia, Pennsylvania, United States

Matthew H. Levine, MD, PhD

• Kadlecek, Stephen, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Stephen Kadlecek, PhD

• Gade, Terence P., University of Pennsylvania, Philadelphia, Pennsylvania, United States

Terence P. Gade, MD, PhD

Background

Renal ischemia–reperfusion injury (IRI) commonly complicates transplantation, surgery, and sepsis, leading to significant morbidity and mortality. Despite this clinical burden, diagnosis still relies on biopsy, underscoring the need for noninvasive biomarkers to inform prognosis. Here, we employ hyperpolarized (HP) 1-13C pyruvate to assess how IRI severity alters renal metabolism and perfusion in a translational model.

Methods

Wild-type C57BL/6 mice underwent moderate (28 min) or severe (45 min) IRI. HP 1-¹³C pyruvate (80mM) was injected (6.7mL/kg) via central line over 10s. Coronal EPSI images were acquired on a 7T scanner from 5s post-injection, every 3.5s (2×2 mm resolution, 7mm slice). Select kidneys were flash frozen 45s after injection and imaged by DESI mass spectrometry.

Results

Figure 1 shows K_PL in IRI and contralateral (C/L) kidneys. On day 7, severe IRI kidneys had significantly lower K_PL than moderate IRI (p<0.05). Moderate IRI also exhibited a significant K_PL increase at day 7 versus 2h and day 1. In severe IRI, K_PL peaked at 2h and declined thereafter. DESI MSI revealed decreasing m+1 lactate over time, with the highest level at 2h in severe IRI.

Conclusion

These findings invert the expected severity–pyruvate flux relationship: day-7 K_PL is lower in severe IRI than in moderate IRI. Also, the correlation between K_PL and DESI lactate in severe IRI—which is not present in moderate IRI—likely reflects the dynamic HP signal versus a static DESI snapshot. The impaired filtration expected in severe IRI may trap lactate, enhancing modality agreement, whereas faster clearance in moderate IRI decouples the measures. Importantly, both methods show that the C/L kidney’s metabolism shifts in parallel with the injured kidney, challenging the assumption that it behaves as a control.

Figure 1: Measured K_PL values the IRI and C/L kidneys across groups, with corresponding DESI heatmaps of m+1 lactate below.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20252nfc0108