Oxygenated End-Hypothermic Machine Perfusion in Expanded Criteria Donor Kidney Transplant | Nephrology | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

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
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

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

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.

Data Sharing Statement: See Supplement 3.

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.

References
1.
Oniscu  GC , Brown  H , Forsythe  JL .  Impact of cadaveric renal transplantation on survival in patients listed for transplantation.   J Am Soc Nephrol. 2005;16(6):1859-1865. doi:10.1681/ASN.2004121092PubMedGoogle ScholarCrossref
2.
Rao  PS , Merion  RM , Ashby  VB , Port  FK , Wolfe  RA , Kayler  LK .  Renal transplantation in elderly patients older than 70 years of age: results from the Scientific Registry of Transplant Recipients.   Transplantation. 2007;83(8):1069-1074. doi:10.1097/01.tp.0000259621.56861.31PubMedGoogle ScholarCrossref
3.
Port  FK , Bragg-Gresham  JL , Metzger  RA ,  et al.  Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors.   Transplantation. 2002;74(9):1281-1286. doi:10.1097/00007890-200211150-00014PubMedGoogle ScholarCrossref
4.
Metzger  RA , Delmonico  FL , Feng  S , Port  FK , Wynn  JJ , Merion  RM .  Expanded criteria donors for kidney transplantation.   Am J Transplant. 2003;3(suppl 4):114-125. doi:10.1034/j.1600-6143.3.s4.11.xPubMedGoogle ScholarCrossref
5.
Pascual  J , Zamora  J , Pirsch  JD .  A systematic review of kidney transplantation from expanded criteria donors.   Am J Kidney Dis. 2008;52(3):553-586. doi:10.1053/j.ajkd.2008.06.005PubMedGoogle ScholarCrossref
6.
McLaren  AJ , Jassem  W , Gray  DW , Fuggle  SV , Welsh  KI , Morris  PJ .  Delayed graft function: risk factors and the relative effects of early function and acute rejection on long-term survival in cadaveric renal transplantation.   Clin Transplant. 1999;13(3):266-272. doi:10.1034/j.1399-0012.1999.130308.xPubMedGoogle ScholarCrossref
7.
Troppmann  C , Gillingham  KJ , Benedetti  E ,  et al.  Delayed graft function, acute rejection, and outcome after cadaver renal transplantation: the multivariate analysis.   Transplantation. 1995;59(7):962-968. doi:10.1097/00007890-199504150-00007PubMedGoogle ScholarCrossref
8.
Barba  J , Algarra  R , Romero  L ,  et al.  Recipient and donor risk factors for surgical complications following kidney transplantation.   Scand J Urol. 2013;47(1):63-71. doi:10.3109/00365599.2012.700945PubMedGoogle ScholarCrossref
9.
Ojo  AO , Hanson  JA , Meier-Kriesche  H ,  et al.  Survival in recipients of marginal cadaveric donor kidneys compared with other recipients and wait-listed transplant candidates.   J Am Soc Nephrol. 2001;12(3):589-597.PubMedGoogle ScholarCrossref
10.
Rabbat  CG , Thorpe  KE , Russell  JD , Churchill  DN .  Comparison of mortality risk for dialysis patients and cadaveric first renal transplant recipients in Ontario, Canada.   J Am Soc Nephrol. 2000;11(5):917-922.PubMedGoogle ScholarCrossref
11.
Wolfe  RA , Ashby  VB , Milford  EL ,  et al.  Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.   N Engl J Med. 1999;341(23):1725-1730. doi:10.1056/NEJM199912023412303PubMedGoogle ScholarCrossref
12.
Moers  C , Smits  JM , Maathuis  MH ,  et al.  Machine perfusion or cold storage in deceased-donor kidney transplantation.   N Engl J Med. 2009;360(1):7-19. doi:10.1056/NEJMoa0802289PubMedGoogle ScholarCrossref
13.
Jochmans  I , Akhtar  MZ , Nasralla  D ,  et al.  Past, present, and future of dynamic kidney and liver preservation and resuscitation.   Am J Transplant. 2016;16(9):2545-2555. doi:10.1111/ajt.13778PubMedGoogle ScholarCrossref
14.
De Deken  J , Kocabayoglu  P , Moers  C .  Hypothermic machine perfusion in kidney transplantation.   Curr Opin Organ Transplant. 2016;21(3):294-300. doi:10.1097/MOT.0000000000000306PubMedGoogle ScholarCrossref
15.
Treckmann  J , Moers  C , Smits  JM ,  et al.  Machine perfusion versus cold storage for preservation of kidneys from expanded criteria donors after brain death.   Transpl Int. 2011;24(6):548-554. doi:10.1111/j.1432-2277.2011.01232.xPubMedGoogle ScholarCrossref
16.
Gallinat  A , Amrillaeva  V , Hoyer  DP ,  et al.  Reconditioning by end-ischemic hypothermic in-house machine perfusion: a promising strategy to improve outcome in expanded criteria donors kidney transplantation.   Clin Transplant. 2017;31(3). doi:10.1111/ctr.12904PubMedGoogle Scholar
17.
Levey  AS , Bosch  JP , Lewis  JB , Greene  T , Rogers  N , Roth  D ; Modification of Diet in Renal Disease Study Group.  A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation.   Ann Intern Med. 1999;130(6):461-470. doi:10.7326/0003-4819-130-6-199903160-00002PubMedGoogle ScholarCrossref
18.
Levey  AS , Stevens  LA , Schmid  CH ,  et al; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration).  A new equation to estimate glomerular filtration rate.   Ann Intern Med. 2009;150(9):604-612. doi:10.7326/0003-4819-150-9-200905050-00006PubMedGoogle ScholarCrossref
19.
Rao  PS , Schaubel  DE , Guidinger  MK ,  et al.  A comprehensive risk quantification score for deceased donor kidneys: the kidney donor risk index.   Transplantation. 2009;88(2):231-236. doi:10.1097/TP.0b013e3181ac620bPubMedGoogle ScholarCrossref
20.
US Department of Health & Human Services. Organ Procurement and Transplant Network KDPI calculator. Accessed March 15, 2021. https://optn.transplant.hrsa.gov/resources/allocation-calculators/kdpi-calculator/
21.
Gallinat  A , Paul  A , Efferz  P ,  et al.  Role of oxygenation in hypothermic machine perfusion of kidneys from heart beating donors.   Transplantation. 2012;94(8):809-813. doi:10.1097/TP.0b013e318266401cPubMedGoogle ScholarCrossref
22.
Gallinat  A , Moers  C , Smits  JM ,  et al.  Machine perfusion versus static cold storage in expanded criteria donor kidney transplantation: 3-year follow-up data.   Transpl Int. 2013;26(6):E52-E53. doi:10.1111/tri.12094PubMedGoogle ScholarCrossref
23.
Peng  P , Ding  Z , He  Y , Zhang  J , Wang  X , Yang  Z .  Hypothermic machine perfusion versus static cold storage in deceased donor kidney transplantation: a systematic review and meta-analysis of randomized controlled trials.   Artif Organs. 2019;43(5):478-489. doi:10.1111/aor.13364PubMedGoogle ScholarCrossref
24.
Moers  C , Pirenne  J , Paul  A , Ploeg  RJ ; Machine Preservation Trial Study Group.  Machine perfusion or cold storage in deceased-donor kidney transplantation.   N Engl J Med. 2012;366(8):770-771. doi:10.1056/NEJMc1111038PubMedGoogle ScholarCrossref
25.
Zhong  Z , Lan  J , Ye  S ,  et al.  Outcome improvement for hypothermic machine perfusion versus cold storage for kidneys from cardiac death donors.   Artif Organs. 2017;41(7):647-653. doi:10.1111/aor.12828PubMedGoogle ScholarCrossref
26.
Tingle  SJ , Figueiredo  RS , Moir  JA , Goodfellow  M , Talbot  D , Wilson  CH .  Machine perfusion preservation versus static cold storage for deceased donor kidney transplantation.   Cochrane Database Syst Rev. 2019;3:CD011671. doi:10.1002/14651858.CD011671.pub2PubMedGoogle Scholar
27.
Gallinat  A , Moers  C , Treckmann  J ,  et al.  Machine perfusion versus cold storage for the preservation of kidneys from donors ≥ 65 years allocated in the Eurotransplant Senior Programme.   Nephrol Dial Transplant. 2012;27(12):4458-4463. doi:10.1093/ndt/gfs321PubMedGoogle ScholarCrossref
28.
Kox  J , Moers  C , Monbaliu  D ,  et al.  The benefits of hypothermic machine preservation and short cold ischemia times in deceased donor kidneys.   Transplantation. 2018;102(8):1344-1350. doi:10.1097/TP.0000000000002188PubMedGoogle ScholarCrossref
29.
Gallinat  A , Efferz  P , Paul  A , Minor  T .  One or 4 h of “in-house” reconditioning by machine perfusion after cold storage improve reperfusion parameters in porcine kidneys.   Transpl Int. 2014;27(11):1214-1219. doi:10.1111/tri.12393PubMedGoogle ScholarCrossref
30.
Hosgood  SA , Mohamed  IH , Bagul  A , Nicholson  ML .  Hypothermic machine perfusion after static cold storage does not improve the preservation condition in an experimental porcine kidney model.   Br J Surg. 2011;98(7):943-950. doi:10.1002/bjs.7481PubMedGoogle ScholarCrossref
31.
Jochmans  I , Brat  A , Davies  L ,  et al; COMPARE Trial Collaboration and Consortium for Organ Preservation in Europe (COPE).  Oxygenated versus standard cold perfusion preservation in kidney transplantation (COMPARE): a randomised, double-blind, paired, phase 3 trial.   Lancet. 2020;396(10263):1653-1662. doi:10.1016/S0140-6736(20)32411-9PubMedGoogle ScholarCrossref
32.
Jochmans  I , Hofker  HS , Davies  L , Knight  S , Pirenne  J , Ploeg  RJ ; COPE and participating centres.  Oxygenated hypothermic machine perfusion of kidneys donated after circulatory death: an international randomised controlled trial.   Am J Transplant. 2019;19(suppl 3).Google Scholar
33.
Darius  T , Gianello  P , Vergauwen  M ,  et al.  The effect on early renal function of various dynamic preservation strategies in a preclinical pig ischemia-reperfusion autotransplant model.   Am J Transplant. 2019;19(3):752-762. doi:10.1111/ajt.15100PubMedGoogle ScholarCrossref
34.
Darius  T , Vergauwen  M , Smith  T ,  et al.  Brief O2 uploading during continuous hypothermic machine perfusion is simple yet effective oxygenation method to improve initial kidney function in a porcine autotransplant model.   Am J Transplant. 2020;20(8):2030-2043. doi:10.1111/ajt.15800PubMedGoogle ScholarCrossref
35.
Jochmans  I , Moers  C , Smits  JM ,  et al.  The prognostic value of renal resistance during hypothermic machine perfusion of deceased donor kidneys.   Am J Transplant. 2011;11(10):2214-2220. doi:10.1111/j.1600-6143.2011.03685.xPubMedGoogle ScholarCrossref
36.
Hosgood  SA , van Heurn  E , Nicholson  ML .  Normothermic machine perfusion of the kidney: better conditioning and repair?   Transpl Int. 2015;28(6):657-664. doi:10.1111/tri.12319PubMedGoogle ScholarCrossref
37.
Minor  T , von Horn  C , Gallinat  A ,  et al.  First-in-man controlled rewarming and normothermic perfusion with cell-free solution of a kidney prior to transplantation.   Am J Transplant. 2020;20(4):1192-1195. doi:10.1111/ajt.15647PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close