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Machine perfusion on cadaveric kidneys unsuitable for transplantation

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Summary of research outcomes

The metabolic effects of machine perfusion on human kidneys unsuitable for transplantation were interrogated during this study.

Although clearly a highly heterogeneous group, we found that the metabolic pathways active in these kidneys were remarkably similar to a porcine DCD model which validated the animal model as a useful metabolic model for perfusion.

Furthermore, utilising a 13C tracer technique, we found that even in kidneys unsuitable for transplantation, often with significant ischaemic injuries, that it is was possible to alter the active metabolic pathways.

This included the promotion of aerobic metabolic activity when supplemental oxygen was provided using a membrane oxygenator.

Indeed, there was significant upregulation of Krebs cycle activity metabolic indicators including de novo production of glutamic acid in kidneys undergoing oxygenated perfusion.

This correlated with increased levels of ATP production and favourable microstructural appearances.

Objectives

The objectives for this study were largely met and the demonstration of these metabolic findings during perfusion in human kidneys was invaluable.

However, owing to the inherent differences between human discarded organs, and the limited supply of paired organs, the human kidneys in this study were largely used to validate the findings in our porcine model rather than as the study subjects themselves.

Improvement to future patient care and treatment

The results from this study have added to the increasing body of evidence detailing the mechanisms by which hypothermic machine perfusion exerts clinical benefit, and in particular to the role of oxygenation of perfusion solution.

Publications

Patel, K., T. B. Smith, D. A. Neil, A. Thakker, Y. Tsuchiya, E. B. Higgs, N. J. Hodges, A. R. Ready, J. Nath and C. Ludwig (2018). "The effects of oxygenation on ex vivo kidneys undergoing Hypothermic Machine Perfusion." Transplantation.

Keynote Lecture:
Assessment of metabolism during hypothermia: new tools for an old unanswered question. Delivered at the International Meeting on Ischaemia Reperfusion in Transplantation (IMIRT) April 2018, Poitiers, France

More information 

Email ODTresearch@nhsbt.nhs.uk for more information about this research.