Hypothermia or Machine Perfusion in Kidney Donors
Therapeutic hypothermia in brain-dead organ donors has been shown to reduce delayed graft function in kidney recipients after transplantation. Data are needed on the effect of hypothermia as compared with machine perfusion on outcomes after kidney transplantation.
METHODS:At six organ-procurement facilities in the United States, we randomly assigned brain-dead kidney donors to undergo therapeutic hypothermia (hypothermia group), ex situ kidney hypothermic machine perfusion (machine-perfusion group), or both (combination-therapy group). The primary outcome was delayed graft function in the kidney transplant recipients (defined as the initiation of dialysis during the first 7 days after transplantation). We also evaluated whether hypothermia alone was noninferior to machine perfusion alone and whether the combination of both methods was superior to each of the individual therapies. Secondary outcomes included graft survival at 1 year after transplantation.
RESULTS:From 725 enrolled donors, 1349 kidneys were transplanted: 359 kidneys in the hypothermia group, 511 in the machine-perfusion group, and 479 in the combined-therapy group. Delayed graft function occurred in 109 patients (30%) in the hypothermia group, in 99 patients (19%) in the machine-perfusion group, and in 103 patients (22%) in the combination-therapy group. Adjusted risk ratios for delayed graft function were 1.72 (95% confidence interval [CI], 1.35 to 2.17) for hypothermia as compared with machine perfusion, 1.57 (95% CI, 1.26 to 1.96) for hypothermia as compared with combination therapy, and 1.09 (95% CI, 0.85 to 1.40) for combination therapy as compared with machine perfusion. At 1 year, the frequency of graft survival was similar in the three groups. A total of 10 adverse events were reported, including cardiovascular instability in 9 donors and organ loss in 1 donor owing to perfusion malfunction.
CONCLUSIONS:Among brain-dead organ donors, therapeutic hypothermia was inferior to machine perfusion of the kidney in reducing delayed graft function after transplantation. The combination of hypothermia and machine perfusion did not provide additional protection. (Funded by Arnold Ventures; ClinicalTrials.gov number, NCT02525510.).
CET Conclusion
| Reviewer: | Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford |
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| Conclusion: | This paper reports an interesting and well-conducted study in renal transplantation following brain death donation. A large number of donors were included and were randomised to donor hypothermia, kidney hypothermic machine perfusion (HMP) or to both. The study was conducted between 7 states in the USA, with 6 organ procurement organisations. The target for mild hypothermia in the donor was 34-35 degrees centigrade. The primary outcome was delayed graft function (DGF). The trial was terminated early, as there was a clear difference in outcomes at an interim analysis. The results showed that HMP was associated with a significant reduction in DGF compared to donor hypothermia alone. The combination of both techniques did not further reduce DGF compared to HMP alone. 1-year graft survival was similar between all 3 groups. |
Methodological quality
| Jadad score | 2 |
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| Allocation concealment | NO |
| Data analysis | INTENTION TO TREAT |
Study Details
| Aims: | This study aimed to examine the effect of mild hypothermia in comparison to machine perfusion or a combination therapy of both methods, on outcomes following kidney transplantation. |
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| Interventions: | Brain-dead kidney donors were randomised to undergo therapeutic hypothermia, ex situ kidney hypothermic machine perfusion, or both. |
| Participants: | 1349 kidneys were transplanted from 725 brain-death donors into 1348 recipients. |
| Outcomes: | The primary endpoint was delayed graft function. The secondary endpoint was graft survival. |
| Follow Up: | 1 year |
Metadata
| Funding: | Non-industry funding |
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| Publication type: | Comparative Study, Randomized Controlled Trial, Randomised Controlled Trial |
| Trial registration: | ClinicalTrials.gov - NCT02525510 |
| Organ: | Kidney |
| Language: | English |
| Author email: | claus.niemann@ucsf.edu |
| MeSH terms: | Humans; Brain Death; Delayed Graft Function; Graft Survival; Hypothermia; Hypothermia, Induced; Kidney; Kidney Transplantation; Organ Preservation; Perfusion; Tissue Donors |