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To keep the transplantation community informed about recently published level 1 evidence in organ transplantation ESOT and the
Effect of an Exercise Intervention or Combined Exercise and Diet Intervention on Health-Related Quality of Life-Physical Functioning After Kidney Transplantation: The Active Care After Transplantation (ACT) Multicentre Randomised Controlled Trial.
The aim of this study was to determine the role of exercise intervention or exercise plus diet intervention on the physical functioning domain of health-related quality of life following kidney transplantation.
Participants were randomised into three groups: usual care, exercise intervention, and exercise plus diet intervention.
221 kidney transplant recipients.
The primary endpoint was change in the physical functioning domain of health-related quality of life (HRQoL). The secondary endpoints were HRQoL composite scores, physical activity, physical fitness, cardiometabolic risk factors and body composition.
15 months.
This multicentre RCT from the Netherlands randomised kidney transplant recipients to one of three groups: usual care, exercise or exercise plus diet. The exercise component comprised a 3-month supervised exercise program, with additional dietary counselling over 15 months in the exercise plus diet group. Interestingly for an RCT, the primary endpoint was a quality-of-life measure (the physical functioning component of the SF-36 questionnaire). At 3 months a small difference in physical functioning was seen in the exercise group, but this difference disappeared by 15 months. Study design and conduct are good, with variable block randomisation and allocation concealment via centralised randomisation. Interventions are well described, and primary analysis is by intent-to-treat. There are some limitations – 35% recruited patients were excluded from the intent-to-treat analysis due to missing primary outcome data at baseline or follow-up, a common issue in studies using QOL questionnaires. This may have led to a lack of statistical power. Also of note, the study only recruited patients in their first year post-transplant, so the results may not generalise to patients later post-transplant.
3.
Strict intention-to-treat analysis.
Yes.
ClinicalTrials.gov - NCT01047410.
Hypothermic Oxygenated Machine Perfusion Influences the Immunogenicity of Donor Livers In Humans.
Non-industry funded.
This observational study aimed to examine the influence of hypothermic oxygenated machine perfusion (HOPE) on the molecular profile of liver allografts as well as on the immune responses induced following liver transplantation.
Participants from two randomised controlled trials comparing donor livers randomly assigned to either HOPE or to static cold storage (SCS), were included.
27 liver transplant recipients.
Molecular and immunogenic profiles of donor livers.
3 months posttransplantation.
This interesting study investigated the immune responses in 27 liver transplant recipients participating in two randomised controlled trials of hypothermic oxygenated machine perfusion (HOPE) in a single centre. The investigators studied perfusate, liver biopsies and recipient T-cell profiles. They showed that, compared to static cold storage, HOPE livers demonstrated reduction in hepatic immune cells in the perfusate and a reduced activation of the reactive oxygen species pathway. In the recipient, there was upregulation in donor-specific T-reg cell expression following HOPE. These findings are interesting, but as this represents only a small single-centre subset of the overall RCT recruitment, can only be exploratory. The patients included only a very small number of DCD liver recipients. They are, however, in keeping with the reduction in acute rejection rates seen in other studies of HOPE in the liver and kidney.
ClinicalTrials.gov - NCT01317342; ClinicalTrials.gov - NCT02584283.
Non-industry funded.
One area that is less studied is the immunological impact of machine perfusion. By increasing ATP storage and reducing ischaemia-reperfusion injury, it is possible that machine preservation has the potential to reduce the innate and adaptive immune response following reperfusion. This has been demonstrated in rodent liver transplant models, where lower doses of immunosuppression are required for successful transplantation following HOPE [
In a recent, posthoc analysis of samples from 2 randomised clinical trials, Elgosbi et al. investigated the role of HOPE in the immunogenicity of liver transplantation [
The sample size in the study is too small to determine whether these immunological effects translate into a clinically meaningful difference in rejection rates or graft function, but nevertheless provide an interesting insight into the mechanisms behind reduced immune activation seen with oxygenated machine perfusion. The majority of patients in the cohort received DBD liver transplants, so it would be interesting to see if the benefit is greater in more injured DCD grafts.
Overall, this is an interesting study, and hopefully paves the way for more detailed analysis alongside future clinical trials of machine perfusion.
3/5.
The author confirms being the sole contributor of this work and has approved it for publication.
The author has undertaken previous paid consultancy work for OrganOx Ltd.
The author(s) declare that no Generative AI was used in the creation of this manuscript.
Edited by Reshma Rana Magar.