Oxygenated End-Hypothermic Machine Perfusion in Expanded Criteria Donor Kidney Transplant: A Randomized Clinical Trial
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.
CET Conclusion
| Reviewer: | Dr Liset Pengel, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford |
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| Conclusion: | This good quality randomised, partially-blinded, controlled trial was conducted as part of the Consortium for organ preservation in Europe (COPE). The study compared kidneys from expanded criteria donors that underwent static cold storage (SCS) alone or SCS plus oxygenated hypothermic machine perfusion (end-HMPO2) after arrival in the recipient transplant centre. Kidneys were randomised on arrival at the recipient centre according to a computer-generated randomisation scheme using an online randomisation tool. A sample size analysis was based on data from a previous trial and showed that 262 kidneys were needed to detect an improvement in 1-year graft survival from 80% to 92%. The intention to treat analysis excluded kidneys that were randomised but not transplanted and consisted of 262 kidneys. Fourteen kidneys of the end-HMPO2 group were cold stored because machine perfusion was not possible and six kidneys received machine perfusion <2 hours for logistical reasons. One-year graft survival was similar between groups and the there were no statistically significant differences for any of the secondary outcomes, i.e. delayed graft function, primary nonfunction, estimated glomerular filtration rate, and acute rejection. The authors comment that as the 1-year graft survival rate in the control group exceeded the baseline assumption, the study is statistically underpowered. |
Methodological quality
| Jadad score | 3 |
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| Allocation concealment | YES |
| Data analysis | PER PROTOCOL |
Study Details
| Aims: | This study aimed to determine whether short-term oxygenated hypothermic machine perfusion preservation (end-HMPO2) following static cold storage (SCS) was more effective in improving kidney transplant outcomes in expanded criteria donor kidneys retrieved from brain dead donors, compared to SCS alone. |
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| Interventions: | Patients were randomly assigned to either end-HMPO2 after SCS or SCS alone. |
| Participants: | 305 expanded criteria donor kidneys retrieved from brain dead donors. |
| Outcomes: | The primary outcome was graft survival at 1 year posttransplant. The secondary outcomes were patient survival, primary nonfunction, delayed graft function, acute rejection and estimated glomerular filtration rate. |
| Follow Up: | 12 months |
Metadata
| Funding: | Non-industry funding |
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| Publication type: | Multicenter Study, Randomized Controlled Trial, Randomised Controlled Trial |
| Organ: | Kidney |
| Language: | English |
| Author email: | peri.husen@uk-essen.de |
| MeSH terms: | Aged; Aged, 80 and over; Cold Ischemia; Delayed Graft Function; Female; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Humans; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Organ Preservation; Perfusion; Prospective Studies; Refrigeration; Single-Blind Method; Survival Rate; Aged, 80 and Over |