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Improving outcomes in kidney transplantation through advances in donor organ perfusion

Nature Reviews Nephrology (2025)Cite this article

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Abstract

The global shortage of suitable donor kidneys is the primary challenge in kidney transplantation, and it is exacerbated by ageing donors with increased numbers of health issues. Improving organ assessment, preservation and conditioning could enhance organ utilization and patient outcomes. Hypothermic machine perfusion (HMP) is associated with better results than static cold storage by reducing delayed graft function and improving short-term graft survival, especially in kidneys recovered from marginal-quality donors. Although HMP is useful for organ preservation, it is difficult to assess organ viability during HMP because of the reduced metabolic activity at low temperatures, and the adoption of HMP has faced logistical challenges. The addition of oxygen during HMP is aimed at reducing ischaemia–reperfusion injury, but has shown mixed results in kidney transplantation, often depending on the duration of perfusion, although some studies found that the addition of oxygen improved outcomes in higher-risk donors. Normothermic machine perfusion helps to restore kidney function by delivering oxygen and nutrients at body temperature, potentially reducing ischaemia–reperfusion injury. Early studies suggest its safety, but clinical benefits remain unproven. Normothermic machine perfusion also holds promise for assessing organ viability pre-transplantation by enabling real-time evaluation. In this Review, we will summarize the different methods of kidney preservation, providing details of the effect that each method has on graft and patient outcomes and the strengths and limitations of each method.

Key points

  • The primary limitation in kidney transplantation globally is the scarcity of suitable donor organs, which is worsening with an ageing donor population with increasing co-morbidities; therefore, we must focus on improving donor organ assessment, preservation and conditioning.

  • Hypothermic machine perfusion (HMP) has demonstrated clear benefits over static cold storage in reducing delayed graft function and improving graft survival and is the new clinical standard in kidney preservation, but organ viability cannot be assessed during HMP.

  • Continuous hypothermic oxygenated machine perfusion demonstrated improved 1-year kidney function and reduced rejection rates compared with HMP alone; however, use of hypothermic oxygenated machine perfusion for a brief period immediately before transplantation showed no benefit over static cold storage alone.

  • Normothermic machine perfusion (NMP) is aimed at restoring aerobic respiration and metabolic activity in donor kidneys by providing oxygen and nutrients at physiological temperatures; early studies show that both NMP and normothermic regional perfusion (an in situ method before donor organs are procured) are safe and feasible.

  • Ex situ NMP holds potential for assessing kidney viability before transplantation by restoring metabolic activity and enabling real-time evaluation of biomarkers, tissue samples and imaging data.

  • Ex situ NMP also provides a promising platform for delivering targeted therapies to isolated donor kidneys before transplantation, enabling real-time intervention and therapeutic modulation of organ function.

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Fig. 1: Different donor types, including the Maastricht classification for donation after circulatory death donors, and the ischaemic injury that each donor type sustains.
Fig. 2: Numbers of patients on kidney transplant waiting lists in the USA and the UK.
Fig. 3: An overview of the different types of preservation and machine perfusion that can be applied in kidney transplantation.

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Acknowledgements

T.J.R. is supported by the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW, supported by Novo Nordisk Foundation grant (NNF21CC0073729)) and T.J.R. and C.M. are funded by the European Union. Views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. This work is supported by ERC grant (SPARK 101140863).

Author information

Author notes

  1. These authors contributed equally: James Hunter, Sarah Hosgood.

Authors and Affiliations

  1. Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK

    James Hunter, Rutger Ploeg, Letizia Lo Faro, Kasia Bera, Richard Dumbill, Peter Friend, Simon Knight, Maria Kaisar, Thomas Vermeire & Paul Johnson

  2. University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK

    James Hunter

  3. Department of Surgery, University of Cambridge, Cambridge, UK

    Sarah Hosgood & Michael Nicholson

  4. University of Groningen, University Medical Center Groningen Comprehensive Transplant Center, Groningen, The Netherlands

    Cyril Moers, Henri Leuvenink & Vincent de Meijer

  5. Department of Internal Medicine — Nephrology, Leiden University Medical Center, Leiden, The Netherlands

    Ton J. Rabelink, Marten A. Engelse & Marlies Reinders

  6. The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, The Netherlands

    Ton J. Rabelink

  7. Institute of Transfusion Medicine & Transplant Engineering, Hannover Medical School, Hannover, Germany

    Constanca Figueiredo

  8. Department of Anaesthesiology and Intensive Care, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway

    Soren Pischke

  9. Norwegian Complement Research Group, Department of Immunology, Division of Laboratory Medicine, University of Oslo, Oslo, Norway

    Soren Pischke

  10. Laboratory of Abdominal Transplantation, Transplantation Research Group, KU Leuven, Leuven, Belgium

    Ina Jochmans & Diethard Monbaliu

  11. Department of Abdominal Transplantation, University Hospitals Leuven, Leuven, Belgium

    Ina Jochmans, Jacques Pirenne & Diethard Monbaliu

  12. Erasmus Medical Center Transplant Institute, Rotterdam, The Netherlands

    Robert Porte & Marlies Reinders

  13. Department of HPB Surgery and Liver Transplant Surgery, Royal Free Hospital, London, UK

    Carlo D. L. Ceresa & David Nasralla

  14. Division of Transplantation Surgery, Karolinska Institute Stockholm, Stockholm, Sweden

    Gabriel Oniscu

  15. Plateforme de Biothérapie, Pôle Médico-Chirurgie Centre Hospitalier Universitaire de Lille, Lille, France

    Julie Kerr-Conte

  16. Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium

    Maarten Naesens & Diethard Monbaliu

  17. Service d’Urologie et de Transplantations Rénales, CHU Nantes Hôtel Dieu, Nantes, France

    Julien Branchereau

  18. Université de Poitiers, INSERM IRMETIST, U1313, Poitiers, France

    Clara Steichen

  19. Inserm UMR1327, University of Tours, Faculty of Medicine, Tours, France

    Sébastien Roger

  20. Department of Nephrology and Renal Transplantation, National and Kapodistrian University of Athens, Athens, Greece

    John Boletis & Stathis Tsiakas

  21. Dutch Transplant Foundation (NTS), Leiden, The Netherlands

    Bernadette Haase

  22. NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Cambridge, UK

    Michael Nicholson

  23. Surgery and Abdominal Transplant Unit, Department of Surgery, University Clinics Saint Luc, Université Catholique de Louvain, Brussels, Belgium

    Tom Darius

  24. Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Stefan Berger

  25. Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

    Peri Husen & Georg Lurje

  26. Department of General, Visceral, Vascular and Transplant Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany

    Anja Gallinat

  27. Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

    Ian Alwyn & Dorottya de Vries

  28. Department of Transplantation Surgery, Aristotle University School of Medicine Thessaloniki, Thessaloniki, Greece

    George Tsoulfas

  29. Division of Visceral Surgery, University Hospital Basel, Basel, Switzerland

    Philipp Dutkowski

  30. General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd, Madrid, Spain

    Amelia Hessheimer & Constantino Fondevila

  31. Department of Surgery, Charité and the Berlin Institute of Health, Berlin, Germany

    Robert Öllinger

  32. Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway

    Pal Dag Line

  33. Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Pal Dag Line

  34. Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Sijbrand Hofker

  35. Faculty of Medicine, University of Lille, Lille, France

    Francois Pattou

Authors
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  2. Sarah Hosgood
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  3. Cyril Moers
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  4. Henri Leuvenink
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Consortia

on behalf of the COPE consortium

  • James Hunter
  • , Sarah Hosgood
  • , Cyril Moers
  • , Henri Leuvenink
  • , Ton J. Rabelink
  • , Rutger Ploeg
  • , Constanca Figueiredo
  • , Letizia Lo Faro
  • , Soren Pischke
  • , Kasia Bera
  • , Ina Jochmans
  • , Richard Dumbill
  • , Robert Porte
  • , Peter Friend
  • , Carlo D. L. Ceresa
  • , David Nasralla
  • , Vincent de Meijer
  • , Gabriel Oniscu
  • , Simon Knight
  • , Marten A. Engelse
  • , Julie Kerr-Conte
  • , Maria Kaisar
  • , Maarten Naesens
  • , Thomas Vermeire
  • , Julien Branchereau
  • , Clara Steichen
  • , Sébastien Roger
  • , John Boletis
  • , Bernadette Haase
  • , Michael Nicholson
  • , Tom Darius
  • , Stathis Tsiakas
  • , Marlies Reinders
  • , Stefan Berger
  • , Peri Husen
  • , Anja Gallinat
  • , Ian Alwyn
  • , George Tsoulfas
  • , Philipp Dutkowski
  • , Amelia Hessheimer
  • , Jacques Pirenne
  • , Diethard Monbaliu
  • , Robert Öllinger
  • , Pal Dag Line
  • , Constantino Fondevila
  • , Georg Lurje
  • , Dorottya de Vries
  • , Sijbrand Hofker
  • , Paul Johnson
  •  & Francois Pattou

Contributions

J.H. and S.H. researched data for the article. All authors contributed substantially to discussion of the content. J.H., S.H., C.M. and H.L. wrote the article. All authors reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to James Hunter.

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Nature Reviews Nephrology thanks Dianne McKay, who co-reviewed with Stephanie Almeida; Chris Callaghan; and the other, anonymous, reviewers for their contribution to the peer review of this work.

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Hunter, J., Hosgood, S., Moers, C. et al. Improving outcomes in kidney transplantation through advances in donor organ perfusion. Nat Rev Nephrol (2025). https://doi.org/10.1038/s41581-025-00993-8

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