Hypothermic Machine Perfusion of Kidneys Compensates for Extended Storage Time: A Single Intervention With a Significant Impact

The high demand for organs in kidney transplantation and the expansion of the donor pool have led to the widespread implementation of machine perfusion technologies. In this study, we aim to provide an up-to-date systematic review of the developments in this expanding field over the past 10 years, with the aim of answering the question: “which perfusion technique is the most promising technique in kidney transplantation?” A systematic review of the literature related to machine perfusion in kidney transplantation was performed. The primary outcome measure was delayed graft function (DGF), and secondary outcomes included rates of rejection, graft survival, and patient survival rates after 1 year. Based on the available data, a meta-analysis was performed. The results were compared with data from static cold storage, which is still the standard of care in many centers worldwide. A total of 56 studies conducted in humans were included, and 43 studies reported outcomes of hypothermic machine perfusion (HMP), with a DGF rate of 26.4%. A meta-analysis of 16 studies showed significantly lower DGF rates in the HMP group compared to those of static cold storage (SCS). Five studies reported outcomes of hypothermic machine perfusion + O2, with an overall DGF rate of 29.7%. Two studies explored normothermic machine perfusion (NMP). These were pilot studies, designed to assess the feasibility of this perfusion approach in the clinical setting. Six studies reported outcomes of normothermic regional perfusion (NRP). The overall incidence of DGF was 71.5%, as it was primarily used in uncontrolled DCD (Maastricht category I-II). Three studies comparing NRP to in situ cold perfusion showed a significantly lower rate of DGF with NRP. The systematic review and meta-analysis provide evidence that dynamic preservation strategies can improve outcomes following kidney transplantation. More recent approaches such as normothermic machine perfusion and hypothermic machine perfusion + O2 do show promising results but need further results from the clinical setting. This study shows that the implementation of perfusion strategies could play an important role in safely expanding the donor pool.

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“… Forest plot—overall rates of DGF in HMP compared to SCS [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. …”

Section: Figurementioning

confidence: 99%

“… Forest plot—rates of graft survival at 1 year—HMP compared to SCS [ 28 , 29 , 30 , 31 , 35 , 36 , 37 , 39 , 41 ]. …”

Section: Figurementioning

confidence: 99%

Outcomes of Kidney Perfusion Techniques in Transplantation from Deceased Donors: A Systematic Review and Meta-Analysis

Ghoneima

Silva²,

Gosteli

et al. 2023

JCM

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“…The challenge of short organ storage times that limit the application of tissue matching has resulted in reduced success with transplants and translated to the loss of human life. Machine perfusion may provide a modest improvement in the transplant of kidneys and hearts 2,26 , but long-term survival rates are not significantly different 27 . Therefore, a less technically demanding alternative, such as or SZ-SCS, has been proposed as a possible solution to extend storage times and increase transplant success.…”

Section: Discussionmentioning

confidence: 99%

Chill injury in human kidney tubule cells after subzero storage is not mitigated by antifreeze protein addition

Tomalty

Graham

Walker

et al. 2022

Preprint

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By preventing freezing, antifreeze proteins (AFPs) can permit cells and organs to be stored at subzero temperatures. As metabolic rates decrease with decreasing temperature, subzero static cold storage (SCS) could provide more time for tissue matching and potentially lead to fewer discarded organs. Human kidneys are generally stored for under 24 h and the tubule epithelium is known to be particularly sensitive to SCS. Here, telomerase-immortalized proximal-tubule epithelial cells from humans, which closely resemble their progenitors, were used as a proxy to assess the potential benefit of subzero SCS for kidneys. The effects of hyperactive AFPs from a beetle and Cryostasis Storage Solution were compared to University of Wisconsin Solution at standard SCS temperatures (4 °C) and at −6 °C for up to six days. Although the AFPs helped guard against freezing, lower storage temperatures under these conditions were not beneficial. Compared to cells at 4 °C, those stored at −6 °C showed decreased viability as well as increased lactate dehydrogenase release and apoptosis. This suggests that this kidney cell type might be prone to chilling injury and that the addition of AFPs to enable subzero storage may not be effective for increasing storage times.

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“…The evidence base supporting the use of HMP for all deceased donor kidneys is growing, with benefits recently reported in the UK [35,36], France [37], Poland [38] and Brazil [39,40]. HMP can also improve renal function when the CIT is extended [35].…”

Section: Hypothermic Machine Perfusionmentioning

confidence: 99%

Advances in Hypothermic and Normothermic Perfusion in Kidney Transplantation

2021

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Hypothermic and normothermic machine perfusion in kidney transplantation are purported to exert a beneficial effect on post-transplant outcomes compared to the traditionally used method of static cold storage. Kidney perfusion techniques provide a window for organ reconditioning and quality assessment. However, how best to deliver these preservation methods or improve organ quality has not yet been conclusively defined. This review summarises the promising advances in machine perfusion science in recent years, which have the potential to further improve early graft function and prolong graft survival.

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Hypothermic Machine Perfusion of Kidneys Compensates for Extended Storage Time: A Single Intervention With a Significant Impact

Cited by 9 publications

References 21 publications

Outcomes of Kidney Perfusion Techniques in Transplantation from Deceased Donors: A Systematic Review and Meta-Analysis

Outcomes of Kidney Perfusion Techniques in Transplantation from Deceased Donors: A Systematic Review and Meta-Analysis

Chill injury in human kidney tubule cells after subzero storage is not mitigated by antifreeze protein addition

Advances in Hypothermic and Normothermic Perfusion in Kidney Transplantation

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