Hypothermic and Normothermic Machine Perfusion Differentially Shape the Renal Cellular Landscape

Abstract

The shortage of donor organs has led to an increased use of extended-criteria donors and donation after circulatory death for kidney transplantation, both of which are associated with graft injury. Although machine perfusion (MP) offers a preservation strategy, the most beneficial approach for kidneys with respect to effective graft preservation remains unclear. We compared oxygenated hypothermic (HMP) and normothermic machine perfusion (NMP) using a murine kidney perfusion model regarding intra-graft immune cell composition, viability, and inflammatory responses. NMP resulted in more severe tubular injury, accompanied by increased immune cell mobilization out of the graft. NMP increased early apoptosis among kidney-resident immune-cell populations, whereas endothelial cells showed increased late apoptosis after both strategies. Proximal tubular-cell apoptosis remained comparable to naive tissue, and neither modality reduced reactive oxygen species levels. Both protocols induced antioxidant and hypoxia-responsive genes compared with static cold storage, while NMP elicited a stronger inflammatory response. Treatment with the senolytic ABT-263 demonstrated the models feasibility for investigating renal injury, cellular viability, and immune activation during MP.

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BibTeX RIS

BibTeX

@misc{siegle2026hypothermic,
  title = {{Hypothermic and Normothermic Machine Perfusion Differentially Shape the Renal Cellular Landscape}},
  author = {J. Siegle and D. M. Kemper and R. Zhu and Y. Yang and J. Wehenkel and G. Harikumar Parvathy and R. Camiletti and K. Hublitz and E. G. Stamatiades and V. Pross and R. Labes and M. Fähling and R. D. Buelow and P. Boor and K. Kotsch},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.07.757234},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.07.757234v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Hypothermic and Normothermic Machine Perfusion Differentially Shape the Renal Cellular Landscape
AU  - J. Siegle
AU  - D. M. Kemper
AU  - R. Zhu
AU  - Y. Yang
AU  - J. Wehenkel
AU  - G. Harikumar Parvathy
AU  - R. Camiletti
AU  - K. Hublitz
AU  - E. G. Stamatiades
AU  - V. Pross
AU  - R. Labes
AU  - M. Fähling
AU  - R. D. Buelow
AU  - P. Boor
AU  - K. Kotsch
PY  - 2026
DA  - 2026/10/07
PB  - bioRxiv
DO  - 10.64898/2026.10.07.757234
UR  - https://www.biorxiv.org/content/10.64898/2026.10.07.757234v1
AB  - The shortage of donor organs has led to an increased use of extended-criteria donors and donation after circulatory death for kidney transplantation, both of which are associated with graft injury. Although machine perfusion (MP) offers a preservation strategy, the most beneficial approach for kidneys with respect to effective graft preservation remains unclear. We compared oxygenated hypothermic (HMP) and normothermic machine perfusion (NMP) using a murine kidney perfusion model regarding intra-graft immune cell composition, viability, and inflammatory responses. NMP resulted in more severe tubular injury, accompanied by increased immune cell mobilization out of the graft. NMP increased early apoptosis among kidney-resident immune-cell populations, whereas endothelial cells showed increased late apoptosis after both strategies. Proximal tubular-cell apoptosis remained comparable to naive tissue, and neither modality reduced reactive oxygen species levels. Both protocols induced antioxidant and hypoxia-responsive genes compared with static cold storage, while NMP elicited a stronger inflammatory response. Treatment with the senolytic ABT-263 demonstrated the models feasibility for investigating renal injury, cellular viability, and immune activation during MP.
ER  -

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