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Nature Medicine Jun 2023Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation... (Randomized Controlled Trial)
Randomized Controlled Trial
Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation after circulatory death (DCD) donors have been used to increase transplant rates, but these organs are susceptible to cold ischemic injury in the storage period before transplantation, the clinical consequence of which is high rates of delayed graft function (DGF). Normothermic machine perfusion (NMP) is an emerging technique that circulates a warmed, oxygenated red-cell-based perfusate through the kidney to maintain near-physiological conditions. We conducted a randomized controlled trial to compare the outcome of DCD kidney transplants after conventional static cold storage (SCS) alone or SCS plus 1-h NMP. A total of 338 kidneys were randomly allocated to SCS (n = 168) or NMP (n = 170), and 277 kidneys were included in the final intention-to-treat analysis. The primary endpoint was DGF, defined as the requirement for dialysis in the first 7 d after transplant. The rate of DGF was 82 of 135 (60.7%) in NMP kidneys versus 83 of 142 (58.5%) in SCS kidneys (adjusted odds ratio (95% confidence interval) 1.13 (0.69-1.84); P = 0.624). NMP was not associated with any increase in transplant thrombosis, infectious complications or any other adverse events. A 1-h period of NMP at the end of SCS did not reduce the rate of DGF in DCD kidneys. NMP was demonstrated to be feasible, safe and suitable for clinical application. Trial registration number: ISRCTN15821205 .
Topics: Humans; Kidney Transplantation; Organ Preservation; Kidney; Perfusion; Tissue Donors
PubMed: 37231075
DOI: 10.1038/s41591-023-02376-7 -
International Angiology : a Journal of... Jun 2023To perform a scoping review analyzing the current evidence reporting on acute kidney injury (AKI) after elective open surgery (OS) of complex abdominal aortic aneurysms... (Review)
Review
INTRODUCTION
To perform a scoping review analyzing the current evidence reporting on acute kidney injury (AKI) after elective open surgery (OS) of complex abdominal aortic aneurysms (c-AAAs) and evaluate the impact of renal perfusion, and the different types of solutions on renal morbidity.
EVIDENCE ACQUISITION
Research questions were defined, and a literature search was performed following the PRISMA guidelines for scoping reviews. Multicenter, single-center observational studies were considered eligible. No abstracts only and unpublished literature were included.
EVIDENCE SYNTHESIS
Two hundred and fifty studies were screened, 20 studies met screening criteria and were included, reporting 1552 patients treated for c-AAAs. The majority did not receive renal perfusion and the others received different types of renal perfusions. Acute kidney injury is a common complication after c-AAAs OS, with an incidence up to 32.5%. Heterogeneity in AKI classifications reduce the ability to compare outcomes after perfusion and nonperfusion strategies. Pre-existing CKD, ischemic injury due to suprarenal aortic clamping are major determinants of AKI after aortic surgery. Most papers reported chronic kidney disease (CKD) at admission. Another debated topic is the indication for renal perfusion during c-AAAs OS. Controversial results for cold renal perfusion have been found.
CONCLUSIONS
In the context of c-AAAs, this review identified the need to standardize the definition of AKI to reduce reporting bias. Besides this, it showed the need to assess the indication for renal perfusion and the type of perfusion solution to be used.
Topics: Humans; Acute Kidney Injury; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Multicenter Studies as Topic; Perfusion; Renal Insufficiency, Chronic
PubMed: 37222507
DOI: 10.23736/S0392-9590.23.05021-6 -
The Journal of Extra-corporeal... Mar 2008
Topics: Cooperative Behavior; Diffusion of Innovation; Evidence-Based Medicine; Humans; Perfusion
PubMed: 18389659
DOI: No ID Found -
EBioMedicine Dec 2023Normothermic regional perfusion (NRP) and hypothermic-oxygenated-perfusion (HOPE), were both shown to improve outcomes after liver transplantation from donors after...
BACKGROUND
Normothermic regional perfusion (NRP) and hypothermic-oxygenated-perfusion (HOPE), were both shown to improve outcomes after liver transplantation from donors after circulatory death (DCD). Comparative clinical and mechanistical studies are however lacking.
METHODS
A rodent model of NRP and HOPE, both in the donor, was developed. Following asystolic donor warm ischemia time (DWIT), the abdominal compartment was perfused either with a donor-blood-based-perfusate at 37 °C (NRP) or with oxygenated Belzer-MPS at 10 °C (donor-HOPE) for 2 h. Livers were then procured and underwent 5 h static cold storage (CS), followed by transplantation. Un-perfused and HOPE-treated DCD-livers (after CS) and healthy livers (DBD) with direct implantation after NRP served as controls. Endpoints included the entire spectrum of ischemia-reperfusion-injury.
FINDINGS
Healthy control livers (DBD) showed minimal signs of inflammation during 2 h NRP and achieved 100% posttransplant recipient survival. In contrast, DCD livers with 30 and 60 min DWIT suffered from greater mitochondrial injury and inflammation as measured by increased perfusate Lactate, FMN- and HMGB-1-levels with subsequent Toll-like-receptor activation during NRP. In contrast, donor-HOPE (instead of NRP) led to significantly less mitochondrial-complex-I-injury and inflammation. Results after donor-HOPE were comparable to ex-situ HOPE after CS. Most DCD-liver recipients survived when treated with one HOPE-technique (86%), compared to only 40% after NRP (p = 0.0053). Following a reduction of DWIT (15 min), DCD liver recipients achieved comparable survivals with NRP (80%).
INTERPRETATION
High-risk DCD livers benefit more from HOPE-treatment, either immediately in the donor or after cold storage. Comparative prospective clinical studies are required to translate the results.
FUNDING
Funding was provided by the Swiss National Science Foundation (grant no: 32003B-140776/1, 3200B-153012/1, 320030-189055/1, and 31IC30-166909) and supported by University Careggi (grant no 32003B-140776/1) and the OTT (grant No.: DRGT641/2019, cod.prog. 19CT03) and the Max Planck Society. Work in the A.G. laboratory was partially supported by the NIH R01NS112381 and R21NS125466 grants.
Topics: Animals; Humans; Liver Transplantation; Rodentia; Prospective Studies; Perfusion; Graft Survival; Organ Preservation; Liver; Tissue Donors; Inflammation
PubMed: 37924707
DOI: 10.1016/j.ebiom.2023.104861 -
Liver Transplantation : Official... Dec 2017The efficacy of cold in situ perfusion and static storage of the liver is a possible determinant of transplantation outcomes. The aim of this study was to determine... (Meta-Analysis)
Meta-Analysis Review
The efficacy of cold in situ perfusion and static storage of the liver is a possible determinant of transplantation outcomes. The aim of this study was to determine whether there is evidence to substantiate a preference for a particular perfusion route (aortic or dual) or perfusion/preservation solution in donation after brain death (DBD) liver transplantation. The Embase, MEDLINE, and Cochrane databases were used (1980-2017). Random effects modeling was used to estimate effects on transplantation outcomes based on (1) aortic or dual in situ perfusion and (2) the use of University of Wisconsin (UW), histidine tryptophan ketoglutarate (HTK), Celsior, and/or Institut Georges Lopez-1 (IGL-1) solutions for perfusion/preservation. A total of 22 articles were included (2294 liver transplants). The quality of evidence ranged from very low to moderate Grading of Recommendations, Assessment, Development and Evaluations score. Meta-analyses were conducted for 14 eligible studies. Although there was no difference in the primary nonfunction (PNF) rate, a higher peak alanine aminotransferase (ALT) was recorded in dual compared with aortic-only UW-perfused livers (standardized mean difference, 0.24; 95% confidence interval, 0.01-0.47); a back-table portal venous flush was undertaken in the majority of aortic-only perfused livers. There were no relevant differences in peak enzymes, PNF, thrombotic graft loss, biliary complications, or 1-year graft survival in comparisons between dual-perfused livers using UW, HTK, Celsior, or IGL-1. In conclusion, there is no significant evidence that aortic-only perfusion of the DBD liver compromises transplantation outcomes, and it may be favored because of its simplicity. However, there is currently insufficient evidence to advocate for the use of any particular perfusion/preservation fluid over the others. Liver Transplantation 23 1615-1627 2017 AASLD.
Topics: Allografts; Cold Ischemia; Graft Survival; Humans; Liver; Liver Transplantation; Organ Preservation; Organ Preservation Solutions; Perfusion; Practice Guidelines as Topic; Tissue and Organ Procurement; Treatment Outcome
PubMed: 28734125
DOI: 10.1002/lt.24829 -
The Journal of Surgical Research Feb 2022Machine perfusion is gaining interest as an efficient method of tissue preservation of Vascularized Composite Allografts (VCA). The aim of this study was to develop a...
BACKGROUND
Machine perfusion is gaining interest as an efficient method of tissue preservation of Vascularized Composite Allografts (VCA). The aim of this study was to develop a protocol for ex vivo subnormothermic oxygenated machine perfusion (SNMP) on rodent hindlimbs and to validate our protocol in a heterotopic hindlimb transplant model.
METHODS
In this optimization study we compared three different solutions during 6 h of SNMP (n = 4 per group). Ten control limbs were stored in a preservation solution on Static Cold Storage [SCS]). During SNMP we monitored arterial flowrate, lactate levels, and edema. After SNMP, muscle biopsies were taken for histology examination, and energy charge analysis. We validated the best perfusion protocol in a heterotopic limb transplantation model with 30-d follow up (n = 13). As controls, we transplanted untreated limbs (n = 5) and hindlimbs preserved with either 6 or 24 h of SCS (n = 4 and n = 5).
RESULTS
During SNMP, arterial outflow increased, and lactate clearance decreased in all groups. Total edema was significantly lower in the HBOC-201 group compared to the BSA group (P = 0.005), 4.9 (4.3-6.1) versus 48.8 (39.1-53.2) percentage, but not to the BSA + PEG group (P = 0.19). Energy charge levels of SCS controls decreased 4-fold compared to limbs perfused with acellular oxygen carrier HBOC-201, 0.10 (0.07-0.17) versus 0.46 (0.42-0.49) respectively (P = 0.002).
CONCLUSIONS
Six hours ex vivo SNMP of rodent hindlimbs using an acellular oxygen carrier HBOC-201 results in superior tissue preservation compared to conventional SCS.
Topics: Allografts; Animals; Composite Tissue Allografts; Extremities; Organ Preservation; Oxygen; Perfusion
PubMed: 34670191
DOI: 10.1016/j.jss.2021.09.005 -
International Journal of Molecular... Sep 2020Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality, and current management has a dramatic impact on healthcare resource... (Review)
Review
Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality, and current management has a dramatic impact on healthcare resource utilization. While our understanding of this disease has improved, the majority of treatment strategies remain supportive in nature and are associated with continued poor outcomes. There is a dramatic need for the development and breakthrough of new methods for the treatment of ARDS. Isolated machine lung perfusion is a promising surgical platform that has been associated with the rehabilitation of injured lungs and the induction of molecular and cellular changes in the lung, including upregulation of anti-inflammatory and regenerative pathways. Initially implemented in an ex vivo fashion to evaluate marginal donor lungs prior to transplantation, recent investigations of isolated lung perfusion have shifted in vivo and are focused on the management of ARDS. This review presents current tenants of ARDS management and isolated lung perfusion, with a focus on how ex vivo lung perfusion (EVLP) has paved the way for current investigations utilizing in vivo lung perfusion (IVLP) in the treatment of severe ARDS.
Topics: Animals; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Inflammation; Lung Injury; Perfusion; Respiratory Distress Syndrome; Tissue Donors
PubMed: 32957547
DOI: 10.3390/ijms21186820 -
Critical Care (London, England) Jun 2021In acute respiratory distress syndrome (ARDS), non-ventilated perfused regions coexist with non-perfused ventilated regions within lungs. The number of unmatched regions... (Observational Study)
Observational Study
BACKGROUND
In acute respiratory distress syndrome (ARDS), non-ventilated perfused regions coexist with non-perfused ventilated regions within lungs. The number of unmatched regions might reflect ARDS severity and affect the risk of ventilation-induced lung injury. Despite pathophysiological relevance, unmatched ventilation and perfusion are not routinely assessed at the bedside. The aims of this study were to quantify unmatched ventilation and perfusion at the bedside by electrical impedance tomography (EIT) investigating their association with mortality in patients with ARDS and to explore the effects of positive end-expiratory pressure (PEEP) on unmatched ventilation and perfusion in subgroups of patients with different ARDS severity based on PaO/FiO and compliance.
METHODS
Prospective observational study in 50 patients with mild (36%), moderate (46%), and severe (18%) ARDS under clinical ventilation settings. EIT was applied to measure the regional distribution of ventilation and perfusion using central venous bolus of saline 5% during end-inspiratory pause. We defined unmatched units as the percentage of only ventilated units plus the percentage of only perfused units.
RESULTS
Percentage of unmatched units was significantly higher in non-survivors compared to survivors (32[27-47]% vs. 21[17-27]%, p < 0.001). Percentage of unmatched units was an independent predictor of mortality (OR 1.22, 95% CI 1.07-1.39, p = 0.004) with an area under the ROC curve of 0.88 (95% CI 0.79-0.97, p < 0.001). The percentage of ventilation to the ventral region of the lung was higher than the percentage of ventilation to the dorsal region (32 [27-38]% vs. 18 [13-21]%, p < 0.001), while the opposite was true for perfusion (28 [22-38]% vs. 36 [32-44]%, p < 0.001). Higher percentage of only perfused units was correlated with lower dorsal ventilation (r = - 0.486, p < 0.001) and with lower PaO/FiO ratio (r = - 0.293, p = 0.039).
CONCLUSIONS
EIT allows bedside assessment of unmatched ventilation and perfusion in mechanically ventilated patients with ARDS. Measurement of unmatched units could identify patients at higher risk of death and could guide personalized treatment.
Topics: Adult; Aged; Electric Impedance; Female; Humans; Italy; Male; Middle Aged; Perfusion; Prognosis; Prospective Studies; Respiration, Artificial; Respiratory Distress Syndrome; Simplified Acute Physiology Score
PubMed: 34082795
DOI: 10.1186/s13054-021-03615-4 -
PloS One 2021Normothermic machine perfusion (NMP) of donor kidneys provides the opportunity for improved graft preservation and objective pre-transplant ex-vivo organ assessment....
Normothermic machine perfusion (NMP) of donor kidneys provides the opportunity for improved graft preservation and objective pre-transplant ex-vivo organ assessment. Currently, a multitude of perfusion solutions exist for renal NMP. This study aimed to evaluate four different perfusion solutions side-by-side and determine the influence of different perfusate compositions on measured renal perfusion parameters. Porcine kidneys and blood were obtained from a slaughterhouse. Kidneys underwent NMP at 37°C for 7 hours, with 4 different perfusion solutions (n = 5 per group). Group 1 consisted of red blood cells (RBCs) and a perfusion solution based on Williams' Medium E. Group 2 consisted of RBCs, albumin and a balanced electrolyte composition. Group 3 contained RBCs and a medium based on a British clinical NMP solution. Group 4 contained RBCs and a medium used in 24-hour perfusion experiments. NMP flow patterns for solutions 1 and 2 were similar, solutions 3 and 4 showed lower but more stable flow rates. Thiobarbituric acid reactive substances were significantly higher in solution 1 and 4 compared to the other groups. Levels of injury marker N-acetyl-β-D glucosaminidase were significantly lower in solution 2 in comparison with solution 3 and 4. This study illustrates that the perfusate composition during NMP significantly impacts the measured perfusion and injury parameters and thus affects the interpretation of potential viability markers. Further research is required to investigate the individual influences of principal perfusate components to determine the most optimal conditions during NMP and eventually develop universal organ assessment criteria.
Topics: Animals; Kidney; Kidney Transplantation; Organ Preservation; Perfusion; Swine
PubMed: 34003874
DOI: 10.1371/journal.pone.0251595 -
Transplantation Mar 2024Dynamic preservation methods such as normothermic, subnormothermic, and hypothermic machine perfusion circuits have emerged as viable alternatives to conventional static... (Review)
Review
Dynamic preservation methods such as normothermic, subnormothermic, and hypothermic machine perfusion circuits have emerged as viable alternatives to conventional static cold storage. These organ perfusion technologies serve as preservation methods and enable organ assessment, reconditioning, and repair before transplantation. Gene therapy is a novel strategy with the potential to transform the field of graft optimization and treatment. Thereby specific pathways involved in the transplantation process can be targeted and modified. This review aims to provide an overview of gene delivery methods during ex vivo machine perfusion of kidney and liver grafts. Recent literature on state-of-the-art gene therapy approaches during ex situ organ preservation, especially with respect to ischemia-reperfusion injury, as well as acute and chronic graft rejection have been analyzed. Additionally, potential challenges that could affect further refinement of this therapeutic modality are outlined.
Topics: Perfusion; Kidney; Organ Preservation; Kidney Transplantation; Extracorporeal Circulation
PubMed: 37482634
DOI: 10.1097/TP.0000000000004738