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Metabolite-enhanced normothermic machine perfusion improves kidney transplant viability
Jan Czogalla, Fabian Hausmann, Simon Lagies, Sydney E. Gies, Sabrina Christiansen, Nico Kaiser, Fabian Haas, Yusuke Okabayashi, Dominik Kylies, Smilla Hofmann, Rossana Franzin, Niklas Sabra, Sarah Bouari, Yitian Fang, Gisela Ambagtsheer, Ilka Edenhofer, Silvia Chilla, Anne K. Mühlig, Marina Zimmermann, Milagros N. Wong, Takashi Yokoo, Oliver Kretz, Maja Lindenmeyer, Florian Grahammer, Martin J. Hoogduijn, Ron de Bruin, Malte Kuehl, Sonja Hänzelmann, Bernd Kammerer, Loreto Gesualdo, Stefan Bonn, Robert C. Minnee, Tobias B. Huber, Victor G. Puelles
Jan Czogalla, Fabian Hausmann, Simon Lagies, Sydney E. Gies, Sabrina Christiansen, Nico Kaiser, Fabian Haas, Yusuke Okabayashi, Dominik Kylies, Smilla Hofmann, Rossana Franzin, Niklas Sabra, Sarah Bouari, Yitian Fang, Gisela Ambagtsheer, Ilka Edenhofer, Silvia Chilla, Anne K. Mühlig, Marina Zimmermann, Milagros N. Wong, Takashi Yokoo, Oliver Kretz, Maja Lindenmeyer, Florian Grahammer, Martin J. Hoogduijn, Ron de Bruin, Malte Kuehl, Sonja Hänzelmann, Bernd Kammerer, Loreto Gesualdo, Stefan Bonn, Robert C. Minnee, Tobias B. Huber, Victor G. Puelles
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Research Article Cell biology Metabolism Nephrology

Metabolite-enhanced normothermic machine perfusion improves kidney transplant viability

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Abstract

Normothermic machine perfusion (NMP) has become a valuable tool to expand the pool of transplantable organs. However, the application of NMP to kidneys presents substantial challenges, mostly due to high variability in the composition of currently used perfusion solutions. Here, we provide a multimodal cross-species cellular atlas of kidney injury associated with NMP using a literature-based consensus buffer. This resource provided a systematic framework that was used to develop a metabolite-enhanced perfusion solution, which protected renal proximal tubular cells, improving cellular viability and transplantation outcomes across species, including human kidneys.

Authors

Jan Czogalla, Fabian Hausmann, Simon Lagies, Sydney E. Gies, Sabrina Christiansen, Nico Kaiser, Fabian Haas, Yusuke Okabayashi, Dominik Kylies, Smilla Hofmann, Rossana Franzin, Niklas Sabra, Sarah Bouari, Yitian Fang, Gisela Ambagtsheer, Ilka Edenhofer, Silvia Chilla, Anne K. Mühlig, Marina Zimmermann, Milagros N. Wong, Takashi Yokoo, Oliver Kretz, Maja Lindenmeyer, Florian Grahammer, Martin J. Hoogduijn, Ron de Bruin, Malte Kuehl, Sonja Hänzelmann, Bernd Kammerer, Loreto Gesualdo, Stefan Bonn, Robert C. Minnee, Tobias B. Huber, Victor G. Puelles

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Figure 4

Loss of citric acid cycle metabolites leads to cellular injury during NMP.

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Loss of citric acid cycle metabolites leads to cellular injury during NM...
(A) Metabolomics of tissue before vs. after NMP with consensus buffer showed 24 significantly upregulated and 55 significantly downregulated metabolites. (B) Metabolite organelle mapping identified mitochondria, peroxisomes and ER as the 3 top organelles predicted to be affected by NMP with consensus buffer. (C) Pathway analysis on metabolomics results returned mainly downregulation of citric acid cycle products. (D) Metabolites from the citric acid cycle showed global downregulation by perfusion. Multiple unpaired t tests were used for statistical analysis.

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