Effect of Hypothermic Machine Perfusion on the Preservation of Kidneys Donated After Cardiac Death: A Single-Center, Randomized, Controlled Trial

Artif Organs. 2017 Aug;41(8):753-758 doi: 10.1111/aor.12836.
Abstract

To assess the application of a hypothermic machine perfusion device (LifePort) in kidney transplantation from donation after cardiac death (DCD) donors, 24 pairs of DCD kidneys were randomly divided into two groups: one of the paired kidneys from the same donor was perfused with the LifePort machine (hypothermic machine perfusion [HMP]), and the contralateral kidney was prepared using common static cold preservation (CCP). The two groups were compared with respect to the incidence of delayed graft function (DGF), level of graft function, and pathological changes in time-zero biopsy specimens. The incidence of DGF was 16.7 and 37.5% in the HMP and CCP groups, respectively; the difference between the two groups was statistically significant (P < 0.05). The incidence of acute rejection was 4.1 (1/24) and 8.3% (2/24) in the HMP and CCP groups, respectively; this difference was not statistically significant (P > 0.05). Forty-eight kidney patients were followed up for 6 months, and the two groups of recipients all survived, yielding a survival rate of 100%. The mean 6-month serum creatinine levels were 98.7 ± 23.6 µmol/L in the HMP group and 105.3 ± 35.1 µmol/L in the CCP group; there was no significant difference between the two groups. HMP can reduce the incidence of DGF in DCD kidneys, and this effect is greater for expanded criteria donors kidneys. HMP can also improve early renal function.

CET Conclusion
Reviewer: Centre for Evidence in Transplantation
Conclusion: This is generally a well conducted study with some good features. However, several larger, and better quality trials have been published in recent years addressing the same research question. There was no power calculation for this study, and as such it is small. It did however have enough power to show a significant reduction in DGF when HMP was used for DCD kidneys (from 37.5% to 16.7%). The overall rate of DGF was low, which may be related to the short cold ischaemic times of only 1-8 hours. The study used paired kidneys, which is a strength. However, kidneys could change randomisation allocation if they did not have a suitable patch or anatomy and the number of such kidneys is not presented in the paper. The method of randomisation is not described. Related to the reduced DGF was a shorter hospital stay for the recipient when HMP was used, and a lower serum creatinine on discharge. There were no other significant differences in the clinical outcomes reported.
Expert Review
Reviewer: Dr Marc J. Clancy, Queen Elizabeth University Hospital, Glasgow, United Kingdom.
Conflicts of Interest: No
Clinical Impact Rating 1
Review: The study by Wang and colleagues is a small (24 transplants per arm) RCT randomising paired kidneys from deceased donors to renal transplant recipients in a non-blinded manner to either standard static cold perfusion or hypothermic machine perfusion (HMP) using the lifeport device. The results of the study suggest a reduction in DGF with HMP with no other differences in clinical outcomes, renal function, graft survival etc. The title of the study refers to DCD kidneys however, the donors used are predominantly brainstem dead, subsequently undergoing cardiac arrest (Maastricht category 4) which limits applicability of results since most UK and European DCD kidney donors are category 3. Furthermore, these organs represent optimal kidneys by 21st century standard with a mean age of 48 years and cold ischaemic time of little more than 6 hours. Such organs should be expected to produce excellent long term results even with early DGF and this is reflected by similar levels of Creatinine at 6 months post transplantation. The study does show a reduction in DGF in the machine produced arm however, the definition of DGF includes the unusual caveat that patients not achieving a creatinine of 400µmol/L by day 7, even if dialysis was not required, are considered to have DGF, which is a non-standard definition across the world literature. Without this altered definition, it is unclear that any measurable benefit of hypothermic perfusion would have been shown. The discussion section focuses on the interesting area of viability assessment and whether the flow/resistance characteristics of hypothermic machine perfusion offer additional important information to help with this key area however, the data presented does not focus on this point. No assessment of cost effectiveness in the light of the reduced DGF is made which would have been a key point for further analysis. The world literature on the field of HMP is far broader than that referred to in the paper. Particularly the paper makes no reference to Moers et al* in which 672 patients were randomised to a similar treatment combination using the same Lifeport device as well as two other large UK studies addressing the same issue. *Moers C, et al. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2009;360(1):7-19.
Methodological quality
Jadad score 2
Allocation concealment NO
Data analysis PER PROTOCOL
Study Details
Aims: To examine the effect of a hypothermic machine perfusion device (LifePort) in kidney transplantation from donation after cardiac death (DCD) donors.
Interventions: Paired kidneys from the same donor were randomly divided to receive either hypothermic machine perfusion (HMP) or common cold preservation (CCP).
Participants: 24 pairs of DCD kidneys (donated from 18 men and 6 women, with an average age of 48.2 ± 12.6 years).
Outcomes: Outcomes measured included delayed graft function, acute rejection, pathological changes, serum creatinine at discharge and 6-months, mean urinary production and mean hospital stay.
Follow Up: 6 months
Metadata
Publication type: Randomized Controlled Trial, Randomised Controlled Trial
Organ: Kidney
Language: English
Author email: zxd581@263.net
MeSH terms: Adult; Death; Delayed Graft Function; Female; Graft Rejection; Graft Survival; Humans; Incidence; Kidney; Kidney Transplantation; Male; Middle Aged; Organ Preservation; Perfusion; Survival Rate; Tissue Donors