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Static Cold Storage (SCS) injures the bile duct, while the effect of Normothermic Machine Perfusion (NMP) is unknown. In a sub-study of the COPE trial on liver NMP, we investigated the impact of preservation type on histological bile duct injury score (BDIS). Transplants with at least one bile duct biopsy, either at end of preservation or 1 h post-reperfusion, were considered. BDIS was determined by assessing peribiliary glands injury, stromal and mural loss, haemorrhage, and thrombosis. A bivariate linear model compared BDIS (estimate, CI) between groups. Sixty-five transplants and 85 biopsies were analysed. Twenty-three grafts were preserved with SCS and 42 with NMP, with comparable baseline characteristics except for a shorter cold ischemic time in NMP. The BDIS increased over time regardless of preservation type (p = 0.04). The BDIS estimate was higher in NMP [8.02 (7.40-8.65)] than in SCS [5.39 (4.52-6.26), p < 0.0001] regardless of time. One patient in each group developed ischemic cholangiopathy, with a BDIS of 6 for the NMP-preserved liver. In six other NMP grafts, BDIS ranged 7-12 without development of ischemic cholangiopathy. In conclusion, BDIS increases over time, and the higher BDIS in NMP did not increase ischemic cholangiopathy. Thus, BDIS may overestimate this risk after liver NMP. [ABSTRACT FROM AUTHOR]

The advent of Machine Perfusion (MP) as a superior form of preservation and assessment for cold storage of both high-risk kidney's and the liver presents opportunities in the field of beta-cell replacement. It is yet unknown whether such techniques, when applied to the pancreas, can increase the pool of suitable donor organs as well as ameliorating the effects of ischemia incurred during the retrieval process. Recent experimental models of pancreatic MP appear promising. Applications of MP to the pancreas, needs refinement regarding perfusion protocols and organ viability assessment criteria. To address the "Role of pancreas machine perfusion to increase the donor pool for beta cell replacement," the European Society for Organ Transplantation (ESOT) assembled a dedicated working group comprising of experts to review literature pertaining to the role of MP as a method of improving donor pancreas quality as well as quantity available for transplant, and to develop guidelines founded on evidence-based reviews in experimental and clinical settings. These were subsequently refined during the Consensus Conference when this took place in Prague. [ABSTRACT FROM AUTHOR]

Ischaemia–reperfusion injury (IRI) is an inevitable process in transplantation and results in inflammation and immune system activation. Alpha-1 antitrypsin (AAT) has anti-inflammatory properties. Normothermic machine perfusion (NMP) can be used to deliver therapies and may help in assessing the effects of IRI and immunity. This study investigated the effects of AAT on IRI and inflammation in pig kidneys when administered during preservation, followed by normothermic reperfusion (NR) with autologous whole blood, as a surrogate for transplant. Two different models were used to deliver AAT or placebo to paired slaughterhouse pig kidneys: Model 1: 7-h static cold storage (SCS) + 3-h NR (n = 5 pairs), where either AAT (10 mg/ml) or placebo was delivered in the flush following retrieval; Model 2: 4-h SCS + 3-h NMP + 3-h NR (n = 5 pairs), where either AAT or placebo was delivered during NMP. Injury markers and cytokines levels were analysed in the perfusate, and heat shock protein 70 KDa (HSP-70) was analysed in biopsies. AAT delivered to kidneys showed no adverse effects on perfusion parameters. HSP-70 fold changes were significantly lower in the AAT group during NMP (P < 0.01, paired t-test) but not during NR. Interleukin-1 receptor antagonist (IL-1ra) fold changes were significantly higher in the AAT group during NR model 1 (p < 0.05, two-way ANOVA). In contrast to the AAT group, significant upregulation of interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) between t = 90 min and t = 180 min and interleukin-8 (IL-8) between baseline and t = 90 min was observed in the control group in NR model 2 (p < 0.05, Tukey's multiple comparison test). However, overall inflammatory cytokines and injury markers showed similar levels between groups. Delivery of AAT to pig kidneys was safe without any detrimental effects. NMP and NR provided excellent methods for comparison of inflammation and immune activation in the delivery of a novel therapy. [ABSTRACT FROM AUTHOR]

Hypothermic machine perfusion (HMP) has become the new gold standard in clinical donor kidney preservation and a promising novel strategy in higher risk donor livers in several countries. As shown by meta-analysis for the kidney, HMP decreases the risk of delayed graft function (DGF) and improves graft survival. For the liver, HMP immediately prior to transplantation may reduce the chance of early allograft dysfunction (EAD) and reduce ischemic sequelae in the biliary tract. Ischemia-reperfusion injury (IRI), unavoidable during transplantation, can lead to massive cell death and is one of the main causes for DGF, EAD or longer term impact. Molecular mechanisms that are affected in IRI include levels of hypoxia inducible factor (HIF), induction of cell death, endothelial dysfunction and immune responses. In this review we have summarized and discussed mechanisms on how HMP can ameliorate IRI. Better insight into how HMP influences IRI in kidney and liver transplantation may lead to new therapies and improved transplant outcomes. [ABSTRACT FROM AUTHOR]

Assessment of specific ß-cell death can be used to determine the quality and viability of pancreatic islets prior to transplantation and hence predict the suitability of the pancreas for isolation. Recently, several groups have demonstrated that unmethylated insulin (INS)- DNA is correlated to ß-cell death in type 1 diabetes patients and during clinical islet isolation and subsequent transplantation. Here, we present a step-by-step protocol of our novel developed method for quantification of the relative amount of unmethylated INS-DNA using methylation sensitive restriction enzyme digital polymerase chain reaction This method provides a novel and sensitive way to quantify the relative amount of ß-cell derived unmethylated INS-DNA in cellular lysate. We therefore suggest that this technique can be of value to reliably determine the purity of an islet preparation and may also serve as a measure of the quality of islets prior to transplantation measuring unmethylated INS-DNA as a reflection of the relative amount of lysed ß-cells. [ABSTRACT FROM AUTHOR]

SUMMARY: Assessment of donor kidney quality is based on clinical scores or requires biopsies for histological assessment. Noninvasive strategies to identify and predict graft outcome at an early stage are, therefore, needed. We evaluated the perfusate of donation after brain death (DBD) kidneys during nonoxygenated hypothermic machine perfusion (HMP). In particular, we compared perfusate protein profiles of good outcome (GO) and suboptimal outcome (SO) 1‐year post‐transplantation. Samples taken 15 min after the start HMP (T1) and before the termination of HMP (T2) were analysed using quantitative liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Hierarchical clustering of the 100 most abundant proteins showed discrimination between grafts with a GO and SO at T1. Elevated levels of proteins involved in classical complement cascades at both T1 and T2 and a reduced abundance of lipid metabolism at T1 and of cytoskeletal proteins at T2 in GO versus SO was observed. ATP‐citrate synthase and fatty acid‐binding protein 5 (T1) and immunoglobulin heavy variable 2‐26 and desmoplakin (T2) showed 91% and 86% predictive values, respectively, for transplant outcome. Taken together, DBD kidney HMP perfusate profiles can distinguish between outcome 1‐year post‐transplantation. Furthermore, it provides insights into mechanisms that could play a role in post‐transplant outcomes. [ABSTRACT FROM AUTHOR]

Summary: Static cold storage (SCS) is the standard method for pancreas preservation prior to transplantation; however, it does not permit organ assessment. Normothermic reperfusion (NR) is utilized clinically for other organs to assess viability. Our aim was to develop NR using normothermic machine perfusion technique to simulate reperfusion at the time of transplantation, enabling evaluation of oxygenated hypothermic machine perfusion (HMPO2) as a newer strategy to optimize pancreas preservation. 13 porcine pancreases procured after circulatory death were divided into 3 groups: 4 pancreases preserved using SCS, and 2 groups preserved by HMPO2 (n = 4 and n = 5, differing by type of preservation solution). Duration of perfusion or cold storage was 6 hours before the 1‐hour assessment using NR. Outcome measures were perfusion characteristics, biochemistry and change in tissue water mass as oedema assessment. During NR, the HMPO2 groups demonstrated better perfusion characteristics, normal macroscopic appearances, decreased water mass and one HMPO2 group demonstrated a response to glucose stimulation. Conversely, the SCS group showed an increased water mass and developed early macroscopic appearances of oedema, interstitial haemorrhage and minimal portal outflow. This study suggests that ex situ assessment of pancreases by NR is promising, and that HMPO2 may be better than SCS. [ABSTRACT FROM AUTHOR]

Summary: Regenerative medicine is emerging as a novel field in organ transplantation. In September 2019, the European Cell Therapy and Organ Regeneration Section (ECTORS) of the European Society for Organ Transplantation (ESOT) held its first meeting to discuss the state‐of‐the‐art of regenerative medicine in organ transplantation. The present article highlights the key areas of interest and major advances in this multidisciplinary field in organ regeneration and discusses its implications for the future of organ transplantation. [ABSTRACT FROM AUTHOR]

Summary: There is good evidence to support the use of hypothermic machine perfusion (HMP) over static cold storage as the favoured preservation method for deceased donor kidneys. However, the utility of HMP as a tool to assess the viability of kidneys for transplant is unclear. There is a need to determine whether perfusate biomarkers produced during HMP can predict post‐transplant outcomes and assess the suitability of organs for transplantation. Three different databases (MEDLINE, Embase, Transplant Library) were screened to 31 May 2019. Articles were included if a relationship was reported between one or more perfusate biomarkers and post‐transplant outcomes. Studies were assessed and graded for methodological quality and strength of evidence. Glutathione S‐transferase was the most promising biomarker for predicting delayed graft function, but its predictive ability was at best moderate. Analysis of primary nonfunction rates was challenging due to low occurrence rates and small sample sizes. Existing studies are limited in quality and have not yielded biomarkers for kidneys undergoing HMP that are able to predict post‐transplant outcomes with sufficient accuracy to support routine clinical use. Further studies with larger samples and more robust methodology are needed. (PROSPERO registration: CRD42019121161). [ABSTRACT FROM AUTHOR]

Summary: Older people are increasingly being referred for consideration for pancreas transplantation (PT). We investigated the outcomes after PT in our older recipient cohort. A prospectively maintained database was interrogated. The cohort was analysed for associations between outcome and older recipient age. A total of 444 transplants were performed in patients aged 23–54 years and 83 transplants in patients aged 55–67 years. There was no difference in death‐censored pancreas or kidney graft survival between the groups. Patient death was associated with older recipient age (HR 1.63 per 10‐year increase). In multivariate Cox regression, risk of mortality was also associated with post‐transplant myocardial infarction (HR 7.25, P = 0.006), pancreas failure (HR 1.91, P = 0.003) and kidney failure (HR 3.55, P < 0.001). About 40% of recipients who died in the first year post‐transplant suffered early graft loss. Those alive at a year post‐transplant had inferior survival if they had lost their kidney graft (P < 0.001). Mortality is higher in older patients and is strongly associated with pancreas and kidney graft failure. This suggests that pancreas transplantation is feasible in older recipients, and careful selection of donor organs is important to optimize survival. [ABSTRACT FROM AUTHOR]

Ex-situ normothermic machine perfusion (NMP) of transplant kidneys allows assessment of kidney quality and targeted intervention to initiate repair processes prior to transplantation. Mesenchymal stromal cells (MSC) have been shown to possess the capacity to stimulate kidney repair. Therefore, the combination of NMP and MSC therapy offers potential to repair transplant kidneys. It is however unknown how NMP conditions affect MSC. In this study the effect of NMP perfusion fluid on survival, metabolism and function of thawed cryopreserved human (h)MSC and porcine (p)MSC in suspension conditions was studied. Suspension conditions reduced the viability of pMSC by 40% in both perfusion fluid and culture medium. Viability of hMSC was reduced by suspension conditions by 15% in perfusion fluid, whilst no differences were found in survival in culture medium. Under adherent conditions, survival of the cells was not affected by perfusion fluid. The perfusion fluid did not affect survival of fresh MSC in suspension compared to the control culture medium. The freeze-thawing process impaired the survival of hMSC; 95% survival of fresh hMSC compared to 70% survival of thawed hMSC. Moreover, thawed MSC showed increased levels of reactive oxygen species, which indicates elevated levels of oxidative stress, and reduced mitochondrial activity, which implies reduced metabolism. The adherence of pMSC and hMSC to endothelial cells was reduced after the thawing process, effect which was particularly profound in in the perfusion fluid. To summarize, we observed that conditions required for machine perfusion are influencing the behavior of MSC. The freeze-thawing process reduces survival and metabolism and increases oxidative stress, and diminishes their ability to adhere to endothelial cells. In addition, we found that hMSC and pMSC behaved differently, which has to be taken into consideration when translating results from animal experiments to clinical studies. [ABSTRACT FROM AUTHOR]

In the face of a crisis in organ donation, the transplant community are increasingly utilizing donation after circulatory death ( DCD) donors. Over the last 10 years, with the increasing usage of DCD donors, we have seen the introduction in a number of new terms and definitions. We report the results of the 6th International Conference in Organ Donation held in Paris in 2013 and report a consensus agreement of an established expert European Working Group on the definitions and terminology regarding DCD donation, including refinement of the Maastricht definitions. This document forms part of a special series where recommendations are presented for uncontrolled and controlled DCD donation and organ specific guidelines for kidney, pancreas, liver and lung transplantation. An expert panel formed a consensus on definitions and terms aiming to establish consistent usage of terms in DCD donation. [ABSTRACT FROM AUTHOR]

Pancreas graft failure rates remain substantial. The PDRI can be used at the time of organ offering, to predict one-year graft survival. This study aimed to validate the PDRI for a UK population. Data for 1021 pancreas transplants were retrieved from a national database for all pancreas transplants. Cases were categorized by PDRI quartile and compared for death-censored graft survival. Significant differences were observed between the UK and US cohorts. The PDRI accurately discriminated graft survival for SPK and was associated with a hazard ratio of 1.52 ( P = 0.009) in this group. However, in the PTA and PAK groups, no association between PDRI quartile and graft survival was observed. This is the largest study to validate the PDRI in a European cohort and has shown for the first time that the PDRI can be used as a tool to predict graft survival in SPK transplantation, but not PTA or PAK transplantation. [ABSTRACT FROM AUTHOR]

Hypothermic machine perfusion (HMP) of kidneys is a long-established alternative to static cold storage and has been suggested to be a better preservation method. Today, as our deceased donor profile continues to change towards higher-risk kidneys of lower quality, we are confronted with the limits of cold storage. Interest in HMP as a preservation technique is on the rise. Furthermore, HMP also creates a window of opportunity during which to assess the viability and quality of the graft before transplantation. The technology might also provide a platform during which the graft could be actively repaired, making it particularly attractive for higher-risk kidneys. We review the current evidence on HMP in kidney transplantation and provide an outlook for the use of the technology in the years to come. [ABSTRACT FROM AUTHOR]

The protective, nonerythropoietic effects of erythropoietin ( EPO) have become evident in preclinical models in renal ischaemia/reperfusion injury and kidney transplantation. However, four recently published clinical trials using high-dose EPO treatment following renal transplantation did not reveal any protective effect for short-term renal function and even reported an increased risk of thrombosis. This review focusses on the current status of protective pathways mediated by EPO, the safety concerns using high EPO dosage and discusses the discrepancies between pre-clinical and clinical studies. The protective effects are mediated by binding of EPO to a heteromeric receptor complex consisting of two β-common receptors and two EPO receptors. An important role for the activation of endothelial nitric oxide synthase is proposed. EPO-mediated cytoprotection still has enormous potential. However, only nonerythropoietic EPO derivatives may induce protection without increasing the risk of cardiovascular events. In preclinical models, nonerythropoietic EPO derivatives, such as carbamoylated EPO and ARA290, have been tested. These EPO derivatives improve renal function and do not affect erythropoiesis. Therefore, nonerythropoietic EPO derivatives may be able to render EPO-mediated cytoprotection useful and beneficial for clinical transplantation. [ABSTRACT FROM AUTHOR]

A randomized controlled trial was designed to compare various outcome variables of the retroperitoneal mini-open muscle splitting incision (MSI) technique and the transperitoneal hand-assisted laparoscopic technique (HAL) in performing living donor nephrectomies. Fifty living kidney donors were randomized to MSI or HAL. Primary endpoint was pain experience scored on a visual analogue scale (VAS). After MSI living donors indicated lower median (range) VAS scores at rest than HAL living donors on postoperative day 2.5 [10 (0-44) vs. 15 (0-70), P = 0.043] and day 3 [7 (0-28) vs. 10 (0-91), P = 0.023] and lower VAS scores while coughing on postoperative day 3 [20 (0-73) vs. 42 (6-86), P = 0.001], day 7 [8 (0-66) vs. 33 (3-76), P < 0.001] and day 14 [2 (0-17) vs. 12 (0-51), P = 0.009]. The MSI technique also resulted in reduced morphine requirement, better scores on three domains of the RAND-36, reduced costs and reduced CRP and IL-6 levels. The HAL technique was superior in operating time and postoperative decrease of hemoglobin level. The MSI technique is superior to the HAL technique in performing living donor nephrectomies with regard to postoperative pain experience. This study reopens the discussion of the way to go in performing the living donor nephrectomy. [ABSTRACT FROM AUTHOR]

Summary Kidneys recovered from donation after cardiac death (DCD) are increasingly used to enlarge the deceased donor pool. Such renal grafts, especially those derived from uncontrolled DCD, have inevitably sustained profound warm ischemic injury, which compromises post-transplant function. Normothermic recirculation (NR) of the deceased donor's body before organ cooling could be an interesting approach to mitigate the detrimental effect of warm ischemia. To date, however, there is no evidence coming from preclinical studies to support the principle of NR in kidney transplantation. In this study, we subjected 48 Lewis rat kidneys to 15 or 30 min of warm ischemia, and subsequently 0, 1, or 2 h of NR. After 24 h cold storage, kidneys were transplanted into a recipient animal and 24 h later we measured the percentage of cortical necrosis, and determined gene expression of heme oxigenase-1, heat shock protein-70, transforming growth factor-β, kidney injury molecule-1, interleukin-6, hypoxia inducible factor-1α, monocyte chemoattractant protein-1, and α-smooth muscle actin in kidney tissue. We found that NR had no significant influence on any of these markers. Therefore, we conclude that this animal study by no means supports the presumed beneficial effect of NR on kidneys that have been severely damaged by warm ischemia. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze the possible effects of machine perfusion (MP) versus cold storage (CS) on delayed graft function (DGF) and early graft survival in expanded criteria donor kidneys (ECD). As part of the previously reported international randomized controlled trial 91 consecutive heart-beating deceased ECDs - defined according to the United Network of Organ Sharing definition - were included in the study. From each donor one kidney was randomized to MP and the contralateral kidney to CS. All recipients were followed for 1 year. The primary endpoint was DGF. Secondary endpoints included primary nonfunction and graft survival. DGF occurred in 27 patients in the CS group (29.7%) and in 20 patients in the MP group (22%). Using the logistic regression model MP significantly reduced the risk of DGF compared with CS (OR 0.460, P = 0.047). The incidence of nonfunction in the CS group (12%) was four times higher than in the MP group (3%) ( P = 0.04). One-year graft survival was significantly higher in machine perfused kidneys compared with cold stored kidneys (92.3% vs. 80.2%, P = 0.02). In the present study, MP preservation clearly reduced the risk of DGF and improved 1-year graft survival and function in ECD kidneys. (Current Controlled Trials number: ISRCTN83876362). [ABSTRACT FROM AUTHOR]

Intestinal transplantation has become the therapy of choice for patients with intestinal failure and life-threatening complications from total parenteral nutrition. Results, however, remain inferior as compared with other transplant types with the quality of the organ graft as the most important factor of outcome after transplantation. The intestine is extremely sensitive to ischemia. Unfortunately, a relatively long ischemic preservation period is inevitable. The current standard in organ preservation [cold storage (CS) with University of Wisconsin solution] was developed for kidney/liver preservation and is suboptimal for the intestinal graft despite good results for other organs. This review aimed at appraising the results from the use of previously applied and recently developed preservation solutions and techniques to identify key areas for improvement. As the studies available do not reveal the most effective method for intestinal preservation, an optimal strategy will result from a synergistic effect of different vital elements identified from a review of published material from the literature. A key factor is the composition of the solution using a low-viscosity solution to facilitate washout of blood, including amino acids to improve viability, impermeants and colloids to prevent edema, and buffer for pH-homeostasis. Optimizing conditions include a vascular flush before CS and luminal preservation. The most effective composition of the luminal solution and a practical, clinically applicable optimal technique are yet to reach finality. Short-duration oxygenated arterial and/or luminal perfusion have to be considered. Thus, a tailor-made approach to luminal preservation solution and technique need further investigation in transplant models and the human setting to develop the ultimate technique meeting the physiologic demands of the intestinal graft during preservation. [ABSTRACT FROM AUTHOR]

In kidney transplantation, graft survival using grafts from donation after brain death (DBD) donors is inferior to results after living donation. However, little is known about the effect of the duration of brain death (BDdur) on outcome after transplantation. This is a retrospective Organ Procurement and Transplant Network analysis using kidney donor and recipient data from 1994 to 2006. BDdur was calculated as the period between brain death declaration and aortic cross clamp. Effects of BDdur on delayed graft function (DGF), acute rejection and graft failure were calculated using binary logistic regression and Cox regression models. Median BDdur was 23.8 h. Longer BDdur decreased the risk for DGF and 1- and 3-year graft failure slightly, but not for acute rejection. In multivariate analysis, donor age and acute rejection were confounders. However, in a multivariate subgroup analysis of donors aged ≤55 years BDdur independently predicted DGF; each hour of BDdur decreasing the risk of DGF with 0.4% ( P = 0.008). Longer BDdur is not detrimental and in fact slightly beneficial in DBD donors ≤55 years of age, reducing the chance of DGF in the recipient. This finding may have an impact on organ retrieval procedures, as no rush but rather an improved donor management prior to retrieval will benefit donor kidney viability. [ABSTRACT FROM AUTHOR]

Especially in damaged organs, adequate organ preservation is critically important to maintain viability. Institut Georges Lopez-1 (IGL-1) is a new preservation solution, with an extracellular sodium/potassium ratio and polyethylene glycol as a colloid. The influence of warm and cold ischemia was evaluated in a rat Lewis–Lewis transplant model with a follow up of 14 days. Eight groups of donation after cardiac death donor kidneys were studied with warm ischemia of 0 and 15 min followed by 0- or 24-h cold storage (CS) preservation in IGL-1 or UW-CSS. Blood was collected daily during the first week and at day 14. Recipients were placed in metabolic cages at day 4 and 14 after transplantation allowing urine collection and adequate measurement of glomerular filtration rate. Focussing on inflammation, reactive oxygen species production, proximal tubule damage, proteinuria, histology, and renal function after transplantation we could not show any relevant difference between IGL-1 and UW-CSS. Furthermore, the combination of 15-min warm ischemia and by 24-h cold ischemia did not result in life sustaining kidney function after transplantation, irrespective of the used solution. In the present experiment, static CS preservation of ischemically damaged rat kidneys in either IGL-1 or UW-CSS rendered equal results after transplantation. [ABSTRACT FROM AUTHOR]

New indications for organ transplantation combined with a stagnating number of available donor grafts have severely lengthened the waiting list for almost all types of transplantations. This has led to a renewed interest in non-heart beating (NHB) donation, as a possible solution to bridge the gap between supply and demand. In this review, we present an overview of current NHB donation practice, outcome, existing problems and future perspectives. We focus on possible improvements in donor management, recipient care and new methods of organ preservation that may be better suited for these marginal organs. Successful institution of NHB protocols depends on adapting current transplantation practice at all levels, which is one of the greatest challenges for researchers and professionals in this interesting re-emerging field. [ABSTRACT FROM AUTHOR]

Hypothermic machine perfusion (HMP) provides better protection against ischemic damage of the kidney compared to cold-storage. The required perfusion pressures needed for optimal HMP of the liver are, however, unknown. Rat livers were preserved in University of Wisconsin organ preservation solution enriched with acridine orange (AO) to stain viable cells and propidium iodide (PI) to detect dead cells. Perfusion pressures of 12.5%, 25% or 50% of physiologic perfusion pressures were compared. Intravital fluorescence microscopy was used to assess liver perfusion by measuring the percentage of AO staining. After 1-h, the perfusion pressure of 12.5% revealed 72% ± 3% perfusion of mainly the acinary zones one and two. The perfusion pressure of 25% and 50% showed complete perfusion. Furthermore, 12.5% showed 14.7 ± 3.6, 25% showed 3.7 ± 0.9, and 50% showed 11.2 ± 1.4 PI positive cells. One hour was followed by another series of experiments comprising 24-h preservation. In comparison with 24-h cold-storage, HMP at 25% showed less PI positive cells and HMP at 50% showed more PI positive cells. In summary, perfusion at 25% showed complete perfusion, demonstrated by AO staining, with minimal cellular injury, shown with PI. This study indicates that fine-tuning of the perfusion pressure is crucial to balance (in)complete perfusion and endothelial injury. [ABSTRACT FROM AUTHOR]

In conventional cold-storage organ preservation, the donor organ is flushed with University of Wisconsin (UW) solution at 0–4°C. The initial flush is used to wash out blood from the microcirculation to allow optimal preservation with the UW solution. The component hydroxyethyl starch (HES) of UW is known to cause relatively high viscosity and a possible interaction with blood, i.e. increased red blood cell (RBC) aggregation. The aim of this study was to investigate the influence of the HES component on the viscosity of UW and the aggregation behaviour of blood during washout. Viscosity aspects were measured with a cone-plate rheometer. HES-induced RBC aggregation was studied by means of an optical aggregation measuring device. The experiments were carried out with rat whole blood and mixtures of rat whole blood with UW-solution and UW without HES (UWmod), at 4°C. The viscosity of blood at 4°C is two-times higher than at 37°C; the UW/blood mixture at 4°C is 1.3-times more viscous than blood at 37°C; the 4°C UWmod/blood mixture equals the viscosity of blood at 37°C. The UW/blood mixture shows a ninefold increased aggregation compared with whole blood. These aggregates are larger than the diameter of the sinusoids in the rat liver. A mixture of whole blood and UWmod shows a lower aggregation than blood. Apart from an increased viscosity, HES in UW causes increased RBC aggregation. The aggregates are larger than the diameter of the sinusoids. Initial washout could be optimised by pre-flushing to improve the viability of the liver and to decrease delayed graft function. [ABSTRACT FROM AUTHOR]

The article discusses the findings of a multicenter randomized trial showing that continuous hypothermic machine perfusion (MP) of kidneys from donors after brain death significantly reduces the risk of delayed graft function (DGF). The study also shows that MP improves graft survival when compared with static cold storage (CS). The authors emphasize the importance for clinical decision making to provide longer follow-up data for the expanded criteria donor (ECD) subgroup.

A letter to the editor is presented in response to the article "Machine perfusion in clinical trials: the preservation solution bias" by Chatauret N. and colleagues, which was published in the previous issues.

The authors express their opinion on several strategies in the preservation of organs and the role of machine perfusion in organ transplantation. Topics and issues discussed by the authors include the improvement of short- and long-term outcomes of organ transplantation, full utilization of a wider range of deceased donor organs as a realistic approach to donor shortage, and methods of organ preservation.

The article highlights the collaboration between the European Society for Organ Transplantation (ESOT) and the Centre for Evidence in Transplantation (CET) to help with the design and reporting of randomized controlled trials. The collaboration is geared towards a knowledge centre for European organ transplantations. Moreover, it aims to evaluate protocols which, when approved, would be officially registered and accredited jointly by CET and ESOT.