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Oxygenated End-Hypothermic Machine Perfusion in Expanded Criteria Donor Kidney TransplantA Randomized Clinical Trial

Educational Objective To identify the extent to which preimplantation short-term reconditioning of kidney grafts using oxygenated hypothermic machine perfusion for at least 2 hours after static cold storage leads to improved 1-year graft survival.

1 Credit CME

JAMA Surgery

Published Online: April 21, 2021

Original Investigation

Article Information and Disclosures

Author Affiliations

¹Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
²Nuffield Department of Surgical Sciences, University of Oxford, United Kingdom
³Transplant Research Group, Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
⁴Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
⁵Department of Surgery, University Medical Center Groningen, the Netherlands
⁶Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary
⁷International Nephrology Research and Training Center (INRTC), Budapest, Hungary
⁸Department of General Surgery, Royal Free Hospital, London, United Kingdom
⁹Renal Transplant Unit, Belfast City Hospital, Belfast, United Kingdom
¹⁰Nephrology and Transplant Directorate, University Hospital of Wales, Cardiff, United Kingdom
¹¹Surgery and Abdominal Transplant Unit, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
¹²Oxford University Hospitals, NHS Foundation Trust, Oxford, United Kingdom
¹³Department of Surgery, Charité, Berlin, Germany
¹⁴Department of Surgery, Imperial College London, London, United Kingdom
¹⁵Department of Transplantation and Surgery, Medical University of Vienna, Vienna, Austria

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Key Points

Question Does preimplantation short-term reconditioning of kidney grafts using oxygenated hypothermic machine perfusion for at least 2 hours after an initial period of static cold storage lead to an improvement of 1-year graft survival in kidneys retrieved from expanded criteria donors?

Findings In this randomized clinical trial of 305 kidneys, 1-year graft survival was equal between kidneys that were machine perfused following static cold storage and kidneys that remained on static cold storage prior to implantation without oxygenated hypothermic machine perfusion.

Meaning These findings suggest that the use of oxygenated hypothermic machine perfusion prior to implantation and following a period of static cold storage does not improve graft survival or kidney function in kidneys retrieved from donors who are brain dead meeting the expanded donor criteria.

Abstract

Importance Continuous hypothermic machine perfusion during organ preservation has a beneficial effect on graft function and survival in kidney transplant when compared with static cold storage (SCS).

Objective To compare the effect of short-term oxygenated hypothermic machine perfusion preservation (end-HMPo₂) after SCS vs SCS alone on 1-year graft survival in expanded criteria donor kidneys from donors who are brain dead.

Design, Setting, and Participants In a prospective, randomized, multicenter trial, kidneys from expanded criteria donors were randomized to either SCS alone or SCS followed by end-HMPo₂ prior to implantation with a minimum machine perfusion time of 120 minutes. Kidneys were randomized between January 2015 and May 2018, and analysis began May 2019. Analysis was intention to treat.

Interventions On randomization and before implantation, deceased donor kidneys were either kept on SCS or placed on HMPo₂.

Main Outcome and Measures Primary end point was 1-year graft survival, with delayed graft function, primary nonfunction, acute rejection, estimated glomerular filtration rate, and patient survival as secondary end points.

Results Centers in 5 European countries randomized 305 kidneys (median [range] donor age, 64 [50-84] years), of which 262 kidneys (127 [48.5%] in the end-HMPo₂ group vs 135 [51.5%] in the SCS group) were successfully transplanted. Median (range) cold ischemia time was 13.2 (5.1-28.7) hours in the end-HMPo₂ group and 12.9 (4-29.2) hours in the SCS group; median (range) duration in the end-HMPo₂ group was 4.7 (0.8-17.1) hours. One-year graft survival was 92.1% (n = 117) in the end-HMPo₂ group vs 93.3% (n = 126) in the SCS group (95% CI, −7.5 to 5.1; P = .71). The secondary end point analysis showed no significant between-group differences for delayed graft function, primary nonfunction, estimated glomerular filtration rate, and acute rejection.

Conclusions and Relevance Reconditioning of expanded criteria donor kidneys from donors who are brain dead using end-HMPo₂ after SCS does not improve graft survival or function compared with SCS alone. This study is underpowered owing to the high overall graft survival rate, limiting interpretation.

Trial Registration isrctn.org Identifier: ISRCTN63852508

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Article Information

Corresponding Author: Peri Husen, MD, Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Hufelandstr 55, 45122 Essen, Germany (peri.husen@uk-essen.de).

Accepted for Publication: January 19, 2021.

Published Online: April 21, 2021. doi:10.1001/jamasurg.2021.0949

Author Contributions: Drs Husen, Paul, and Ploeg had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Ploeg and Paul contributed equally.

Concept and design: Husen, Jochmans, Knight, Ablorsu, Pratschke, Mathe, Leuvenink, Minor, Ploeg.

Acquisition, analysis, or interpretation of data: Husen, Boffa, Jochmans, Krikke, Davies, Mazilescu, Brat, Knight, Wettstein, Cseprekal, Banga, Bellini, Szabo, Darius, Quiroga, Mourad, Pratschke, Papalois, Mathe, Pirenne, Ploeg, Paul.

Drafting of the manuscript: Husen, Davies, Mazilescu, Cseprekal, Ablorsu, Darius, Mathe, Leuvenink, Ploeg, Paul.

Critical revision of the manuscript for important intellectual content: Husen, Boffa, Jochmans, Krikke, Brat, Knight, Wettstein, Banga, Bellini, Szabo, Darius, Quiroga, Mourad, Pratschke, Papalois, Mathe, Minor, Pirenne, Ploeg, Paul.

Statistical analysis: Husen, Davies.

Obtained funding: Husen, Ploeg.

Administrative, technical, or material support: Husen, Boffa, Mazilescu, Brat, Knight, Wettstein, Cseprekal, Banga, Bellini, Szabo, Ablorsu, Darius, Quiroga, Mourad, Pratschke, Papalois, Mathe, Minor, Ploeg, Paul.

Supervision: Husen, Jochmans, Knight, Darius, Quiroga, Pratschke, Papalois, Mathe, Leuvenink, Ploeg, Paul.

Conflict of Interest Disclosures: Dr Husen reports grants from European Union 7th Framework Programme during the conduct of the study. Dr Boffa reports other support from Astellas Pharma outside the submitted work. Dr Jochmans reports grants from European Union 7th Framework Programme during the conduct of the study and other support from European Society for Organ Transplantation and European Association for the Study of the Liver outside the submitted work. Dr Knight reports personal fees from OrganOx for clinical trial design outside the submitted work. Dr Leuvenink reports grants from European Union 7th Framework Programme during the conduct of the study. Dr Minor reports grants from the European Union during the conduct of the study. No other disclosures were reported.

Funding/Support: The trial was funded by the European Union 7th Framework Programme (Theme Health.2012.1.4-1, grant agreement 305934). Perfusion devices and disposables were obtained from Organ Assist. MedAssist provided logistical support in terms of delivery and collection of devices, disposables, and samples.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: This trial was conducted by the members of the Consortium for Organ Preservation in Europe. We thank the European Commission for their funding through the Seventh Framework Programme. We also thank Timothy Boland (trial management); Ally Bradley (trial management); Virginia Chiocchia, MSc (statistical analysis); Katherine Corr (trial management) (Nuffield Department of Surgical Sciences, University of Oxford, UK); H. Sijbrand Hofker, MD (local trial coordination) (Department of Surgery, University Medical Center Groningen, the Netherlands); Undine Gerlach, MD (local trial coordination) (Department of Surgery, Charité, Berlin, Germany); Halil Karadag, MD (sample collection) (Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Germany); Martin Kuizenga (assistance in machine preservation) (OrganAssist, the Netherlands); Rajeev Kumar, PhD (database management); Margaux Laspeyres, MA (trial management) (Nuffield Department of Surgical Sciences, University of Oxford, UK); Sarah Mertens (data collection and local coordination) (Transplant Research Group, Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium); Bhumika Patel (biobank management) (Nuffield Department of Surgical Sciences, University of Oxford, UK); and Marianne Thijssen-Grooten (logistics support) (MedAssist, the Netherlands) for their support. We are indebted to the members of the data monitoring committee: Christopher J. E. Watson, MD (chair) (University of Cambridge, UK); Josep M Grinyó, MD (University of Barcelona, Spain); Gabriel C Oniscu, MD (Royal Infirmary of Edinburgh, UK); and Susan Charman, BSc, Dip Ed, MSc (London, UK), as well as to all our patients, the donors and their families. These individuals were not compensated.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.