machine perfusion
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Static cold storage is generally used to preserve kidney allografts from deceased donors. Hypothermic machine perfusion may improve outcomes after transplantation, but few sufficiently powered prospective studies have addressed this possibility. METHODS: In this international randomized, controlled trial, we randomly assigned one kidney from 336 consecutive deceased donors to machine perfusion and the other to cold storage. All 672 recipients were followed for 1 year. The primary end point was delayed graft function (requiring dialysis in the first week after transplantation). Secondary end points were the duration of delayed graft function, delayed graft function defined by the rate of the decrease in the serum creatinine level, primary nonfunction, the serum creatinine level and clearance, acute rejection, toxicity of the calcineurin inhibitor, the length of hospital stay, and allograft and patient survival. RESULTS: Machine perfusion significantly reduced the risk of delayed graft function. Delayed graft function developed in 70 patients in the machine-perfusion group versus 89 in the cold-storage group (adjusted odds ratio, 0.57; P=0.01). Machine perfusion also significantly improved the rate of the decrease in the serum creatinine level and reduced the duration of delayed graft function. Machine perfusion was associated with lower serum creatinine levels during the first 2 weeks after transplantation and a reduced risk of graft failure (hazard ratio, 0.52; P=0.03). One-year allograft survival was superior in the machine-perfusion group (94% vs. 90%, P=0.04). No significant differences were observed for the other secondary end points. No serious adverse events were directly attributable to machine perfusion. CONCLUSIONS: Hypothermic machine perfusion was associated with a reduced risk of delayed graft function and improved graft survival in the first year after transplantation. (Current Controlled Trials number, ISRCTN83876362.) 2009 Massachusetts Medical Society
- MeSH
- analýza přežití MeSH
- délka pobytu MeSH
- dospělí MeSH
- kreatinin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mrtvola MeSH
- multivariační analýza MeSH
- nízká teplota MeSH
- opožděný nástup funkce štěpu krev prevence a kontrola MeSH
- perfuze MeSH
- proporcionální rizikové modely MeSH
- rejekce štěpu MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transplantace ledvin MeSH
- uchovávání orgánů MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
BACKGROUND: While 4 randomized controlled clinical trials confirmed the early benefits of hypothermic oxygenated machine perfusion (HOPE), high-level evidence regarding long-term clinical outcomes is lacking. The aim of this follow-up study from the HOPE-ECD-DBD trial was to compare long-term outcomes in patients who underwent liver transplantation using extended criteria donor allografts from donation after brain death (ECD-DBD), randomized to either HOPE or static cold storage (SCS). METHODS: Between September 2017 and September 2020, recipients of liver transplantation from 4 European centers receiving extended criteria donor-donation after brain death allografts were randomly assigned to HOPE or SCS (1:1). Follow-up data were available for all patients. Analyzed endpoints included the incidence of late-onset complications (occurring later than 6 months and graded according to the Clavien-Dindo Classification and the Comprehensive Complication Index) and long-term graft survival and patient survival. RESULTS: A total of 46 patients were randomized, 23 in both arms. The median follow-up was 48 months (95% CI: 41-55). After excluding early perioperative morbidity, a significant reduction in late-onset morbidity was observed in the HOPE group (median reduction of 23 Comprehensive Complication Index-points [p=0.003] and lower incidence of major complications [Clavien-Dindo ≥3, 43% vs. 85%, p=0.009]). Primary graft loss occurred in 13 patients (HOPE n=3 vs. SCS n=10), resulting in a significantly lower overall graft survival (p=0.029) and adverse 1-, 3-, and 5-year survival probabilities in the SCS group, which did not reach the level of significance (HOPE 0.913, 0.869, 0.869 vs. SCS 0.783, 0.606, 0.519, respectively). CONCLUSIONS: Our exploratory findings indicate that HOPE reduces late-onset morbidity and improves long-term graft survival providing clinical evidence to further support the broad implementation of HOPE in human liver transplantation.
BACKGROUND & AIMS: Despite strong evidence for improved preservation of donor livers by machine perfusion, longer post-transplant follow-up data are urgently needed in an unselected patient population. We aimed to assess long-term outcomes after transplantation of hypothermic oxygenated machine perfusion (HOPE)-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of HOPE-treated livers transplanted between January 2012 and December 2021. Analyses were stratified by donation after brain death (DBD) and donation after circulatory death (DCD), sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischaemic cholangiopathy (IC). RESULTS: We report on 1,202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low risk (10%), 186 as high risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival rates for DBD and DCD livers were 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (log-rank p = 0.003). Within DBD and DCD strata, death-censored graft survival was similar among risk groups (log-rank p = 0.26, p = 0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE treatment has now reached IDEAL-D stage 4, which further supports its implementation in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of hypothermic oxygenated machine perfusion (HOPE) treatment of donation after circulatory and donation after brain death liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomised-controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE treatment has now reached the final IDEAL-D stage 4, which further supports its implementation in routine clinical practice.
- MeSH
- dárci tkání statistika a číselné údaje MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- perfuze * metody přístrojové vybavení MeSH
- přežívání štěpu * MeSH
- senioři MeSH
- terapeutická hypotermie metody MeSH
- transplantace jater * metody škodlivé účinky MeSH
- uchovávání orgánů * metody MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
OBJECTIVES: To establish the optimal machine perfusion temperature for recovery of hearts in a rodent model of donation after declaration of cardiocirculatory death (DCD). METHODS: Hearts from male Lewis rats (n = 14/group) were subjected to 25 min of in situ warm (37°C) ischaemia to simulate DCD. They were then explanted and reperfused with diluted autologous blood for 60 min at 20, 25, 30, 33 or 37°C, after which they were stored at 0-4°C in Custodiol preservation solution for 240 min. Fresh-excised and cold-stored ischaemic hearts were used as controls. The viability of the different groups was assessed by comparing heart rate and left ventricular contractility in a Langendorff circuit, as well as perfusate levels of troponin-t and creatine kinase (CK), and myocardial levels of adenosine triphosphate (ATP) and reduced glutathione. RESULTS: During ex vivo reperfusion, hearts in all groups resumed beating within minutes. The mean heart rate was highest in the 37°C group at 154.72 ± 33.01 beats × min(-1) (bpm), and declined in proportion to temperature to 39.72 ± 5.53 bpm at 20°C. Troponin-t levels were highest in the 37°C group (79.49 ± 20.79 µg/l), the values were significantly lower in all other reconditioned groups with a minimum of 12.472 ± 7.08 µg/l in the 20°C group (P < 0.0001). Tissue ATP levels ranged from 4.32 ± 1.71 µmol/g at 33°C to 4.59 ± 1.41 µmol/g at 30°C, all significantly higher than the mean ATP level of 1.41 ± 0.93 µmol/g in untreated ischaemic hearts (P < 0.0001). During Langendorff assessment, the mean heart rate and contractility of all groups were higher than those of cold-stored ischaemic hearts (P < 0.0001), yet not significantly different from those of fresh controls. The perfusate levels of troponin-t and CK, and myocardial levels of reduced-glutathione and ATP were not significantly different between groups. CONCLUSION: Our results suggest that mild hypothermia during ex vivo reperfusion improves recovery of ischaemic hearts in a rodent DCD model.
- MeSH
- dárci tkání MeSH
- krysa rodu rattus MeSH
- míra přežití MeSH
- modely nemocí na zvířatech MeSH
- náhodné rozdělení MeSH
- obnova funkce MeSH
- odběr tkání a orgánů metody MeSH
- potkani inbrední LEW MeSH
- přežívání štěpu MeSH
- reperfuze myokardu metody MeSH
- smrt * MeSH
- studená ischemie metody MeSH
- techniky in vitro MeSH
- terapeutická hypotermie metody MeSH
- transplantace srdce metody MeSH
- uchovávání orgánů metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: There is still a lack of organs for kidney transplantation. The aim of our experimental animal study was to improve the quality of the kidney grafts from donors after cardiac death (DCD) using immediate start of machine perfusion instead of perfusion based on hydrostatic pressure. METHODS: Ten rabbits were used as an experimental model. In group A, 5 kidneys after ischemic injury were perfused in situ using hydrostatic pressure. In group B, 5 kidneys were perfused in situ using machine pulsatile perfusion. After nephrectomy kidney parenchyma was histologically analyzed. We have evaluated the maximum perfusion flow rate, temperature drop rate, and degree of parenchymal injury. RESULTS: The flow rate in the group of machine-perfused animals (group B) was significantly higher than in the control group (group A), and temperature was significantly decreased in group B (P < .001). Qualitative histopathologic evaluation of the perfusion quality of the grafts was statistically significant, again in favor of machine perfusion in group B (P = .005). DISCUSSION: According to our results, the immediate start of machine perfusion is a superior method of kidney graft preservation in DCDs. All observed modalities were superior in the group with machine perfusion compared with usual clinical practice.
- MeSH
- dárci tkání MeSH
- králíci MeSH
- ledviny * MeSH
- modely nemocí na zvířatech MeSH
- nefrektomie MeSH
- odběr tkání a orgánů metody MeSH
- perfuze metody MeSH
- pulzatilní průtok MeSH
- smrt MeSH
- transplantace ledvin metody MeSH
- transplantáty MeSH
- uchovávání orgánů metody MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Orthotopic liver transplantation (OLT) has emerged as the mainstay of treatment for end-stage liver disease. In an attempt to improve the availability of donor allografts and reduce waiting list mortality, graft acceptance criteria were extended increasingly over the decades. The use of extended criteria donor (ECD) allografts is associated with a higher incidence of primary graft non-function and/or delayed graft function. As such, several strategies have been developed aiming at reconditioning poor quality ECD liver allografts. Hypothermic oxygenated machine perfusion (HOPE) has been successfully tested in preclinical experiments and in few clinical series of donation after cardiac death OLT. METHODS AND ANALYSIS: HOPE ECD-DBD is an investigator-initiated, open-label, phase-II, prospective multicentre randomised controlled trial on the effects of HOPE on ECD allografts in donation after brain death (DBD) OLT. Human whole organ liver grafts will be submitted to 1-2 hours of HOPE (n=23) via the portal vein before implantation and are going to be compared with a control group (n=23) of patients transplanted after conventional cold storage. Primary (peak and Δ peak alanine aminotransferase within 7 days) and secondary (aspartate aminotransferase, bilirubin and international normalised ratio, postoperative complications, early allograft dysfunction, duration of hospital and intensive care unit stay, 1-year patient and graft survival) endpoints will be analysed within a 12-month follow-up. Extent of ischaemia-reperfusion (I/R) injury will be assessed using liver tissue, perfusate, bile and serum samples taken during the perioperative phase of OLT. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of the RWTH Aachen University, Aachen, Germany (EK 049/17). The current paper represent the pre-results phase. First results are expected in 2018. TRIAL REGISTRATION NUMBER: NCT03124641.
- MeSH
- alografty * MeSH
- dárci tkání * MeSH
- dospělí MeSH
- játra * patologie chirurgie MeSH
- konečné stadium selhání jater chirurgie MeSH
- kyslík * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mozková smrt * MeSH
- perfuze MeSH
- přežívání štěpu * MeSH
- prospektivní studie MeSH
- senioři MeSH
- transplantace jater * MeSH
- získávání tkání a orgánů MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Donation after circulatory death donors are becoming a common source of organs for transplant. Despite good long-term outcomes of grafts from donation after circulatory death, this group is affected by a higher occurrence of delayed graft function and primary nonfunction. Our hypothesis is based on the assumption that washing the kidney grafts in the donor's body using a simple mechanical perfusion pump will result in faster and better perfusion of the parenchyma and more efficient cooling compared with hydrostatic perfusion alone. METHODS: A total of 7 experimental animals (pigs) were used. The animals were divided into 2 groups: group A (n = 3) and group B (n = 4). After a 30-minute ischemic period for the selected kidney (clamped renal vessels), intra-arterial perfusion was performed. In group A perfusion was performed using hydrostatic pressure; in group B mechanical controlled perfusion was performed. After perfusion, declamping of the renal vessels caused restoration of flow. For graft quality evaluation, biopsy specimens were harvested, and the cooling speed was observed. Laboratory markers or renal failure were determined. RESULTS: We found no significant differences between temperature drop and total diuresis between groups A and B. A significant difference was found between the groups in both flow parameters (flow maximum and mean flow) (P = .007, respectively P = .019). No laboratory parameters were found to be statistically significantly different. Histopathological analysis strongly supports the hypothesis of better flushing of kidney grafts using mechanical perfusion. CONCLUSIONS: Based on our results, better kidney graft quality can be expected after immediately started mechanical perfusion in situ.
- MeSH
- dárci tkání MeSH
- ledviny MeSH
- opožděný nástup funkce štěpu MeSH
- perfuze MeSH
- prasata MeSH
- přežívání štěpu MeSH
- smrt MeSH
- transplantace ledvin * MeSH
- uchovávání orgánů MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
3rd ed. xxiv, 827 s. : il. ; 29 cm
1st ed. xxiv, 827 s.: obr.
Ischemia-reperfusion injury (IRI) constitutes a significant source of morbidity and mortality after orthotopic liver transplantation (OLT). The allograft is metabolically impaired during warm and cold ischemia and is further damaged by a paradox reperfusion injury after revascularization and reoxygenation. Short-term and long-term complications including post-reperfusion syndrome, delayed graft function, and immune activation have been associated with IRI. Due to the current critical organ shortage, extended criteria grafts are increasingly considered for transplantation, however, with an elevated risk to develop significant features of IRI. In recent years, ex vivo machine perfusion (MP) of the donor liver has witnessed significant advancements. Here, we describe the concept of hypothermic (oxygenated) machine perfusion (HMP/HOPE) approaches and highlight which allografts may benefit from this technology. This review also summarizes clinical applications and the main aspects of ongoing randomized controlled trials on hypothermic perfusion. The mechanistic aspects of IRI and hypothermic MP-which include tissue energy replenishment, optimization of mitochondrial function, and the reduction of oxidative and inflammatory damage following reperfusion-will be comprehensively discussed within the context of current preclinical and clinical evidence. Finally, we highlight novel trends and future perspectives in the field of hypothermic MP in the context of recent findings of basic and translational research.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
