Kidney Week

Abstract: TH-OR101

Mitochondrial Injury in Human and Mouse Kidneys with Ischemia-Reperfusion Injury

Session Information

• The Next Frontier in Kidney Transplantation: Omics, Gene Editing, and Precision Medicine
  October 22, 2026 | Location: Mile High Ballroom 4A, Convention Center
  Abstract Time: 04:40 PM - 04:50 PM

Category: Transplantation

• 2001 Transplantation: Basic

Authors

• Neupane, Slaghaniya, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada

Slaghaniya Neupane

• Bulboaca, Anne-Marie, University of Toronto Faculty of Arts & Science, Toronto, Ontario, Canada

Anne-Marie Bulboaca

• Petrovic, Stefan, University Health Network, Toronto, Ontario, Canada

Stefan Petrovic

• Choi, Hong Sang, University Health Network, Toronto, Ontario, Canada

Hong Sang Choi, MD, PhD

• Nakamura, Kenji, University Health Network, Toronto, Ontario, Canada

Kenji Nakamura, MD

• Manion, Kieran, University Health Network, Toronto, Ontario, Canada

Kieran Manion, PhD

• John, Rohan, University Health Network, Toronto, Ontario, Canada

Rohan John, MD

• Selzner, Markus, University Health Network, Toronto, Ontario, Canada

Markus Selzner, MD

• Robinson, Lisa, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada

Lisa Robinson, MD, FASN

• Konvalinka, Ana, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada

Ana Konvalinka, MD, PhD

Background

Ischemia-reperfusion injury (IRI) harms transplanted kidneys, with deceased donor grafts more impacted than living donor (LD) grafts. Normothermic ex vivo kidney perfusion (NEVKP) results in superior graft outcomes compared to static cold storage (SCS). We showed that NEVKP improves kidney function and preserves mitochondrial protein expression (ETFB and CPT2) in a porcine model of autotransplantation. Here we examined the mitochondrial health of NEVKP, SCS, and LD human grafts, and the impact of IRI on murine kidney mitochondrial gene and protein expression.

Methods

ETFB was evaluated in human kidney biopsies using immunostaining, and circulating cell-free mitochondrial DNA (ccf-mtDNA) was measured in plasma. Plasma proteomics was done with the SomaScan assay. Male and female mice had unilateral IRI (uIRI) and contralateral nephrectomy on post-op day 14 and were sacrificed 24h later.

Results

ETFB expression was decreased in grafts stored by SCS compared to NEVKP, which exceeded LD levels. Ccf-mtDNA was elevated in SCS compared to NEVKP plasma. Plasma proteomics revealed increased expression of proteins mediating mitochondrial triggered apoptosis, NLRP3 inflammasome, fatty acid oxidation, and mitochondrial fission in SCS patients. Mice subjected to uIRI+nephrectomy showed increases in serum creatinine and kidney fibrosis. ETFB protein expression and gene expression of Etfb, Cpt2, and Ppargc1a were reduced in the injured kidney.

Conclusion

Severe IRI was associated with decreased expression of mitochondrial proteins in both humans and mice. Increased ccf-mtDNA in humans indicated mitochondrial injury. The inverse expression of mitochondria-associated proteins in plasma compared to tissue suggests leakage of intracellular contents in IRI. The findings support that NEVKP preserves mitochondria integrity, which may underpin superior kidney function.