73 research outputs found
Hypothermic or normothermic abdominal regional perfusion in high-risk donors with extended warm ischemia times: impact on outcomes?
No full textImproved short and long term function of DCD kidneys with oxygenated machine perfusion
No full textORAL SESSION 20 : Improving preservation in transplant organsInternational audienc
The french speaking society of transplantation and "transplantation sans frontières"
No full textpeer reviewe
Immunosuppressive therapy after solid organ transplantation and the gut microbiota: bidirectional interactions with clinical consequences
No full textInternational audienceOur understanding of the involvement of the gut microbiota (GM) in human health has expanded exponentially over the last few decades, particularly in the fields of metabolism, inflammation, and immunology. Immunosuppressive treatment (IST) prescribed to solid organ transplant (SOT) recipients produces GM changes that affect these different processes. This review aims at describing the current knowledge of how IST changes the GM. Overall, SOT followed by IST results in persistent changes in the GM, with a consistent increase in proteobacteria including opportunistic pathobionts. In mice, Tacrolimus induces dysbiosis and metabolic disorders, and alters the intestinal barrier. The transfer of the GM from Tacrolimus-treated hosts confers immunosuppressive properties, suggesting a contributory role for the GM in this drug's efficacy. Steroids induce dysbiosis and intestinal barrier alterations, and also seem to depend partly on the GM for their immunosuppressive and metabolic effects. Mycophenolate Mofetil, frequently responsible for digestive side effects such as diarrhea and colitis, is associated with pro-inflammatory dysbiosis and increased endotoxemia. Alemtuzumab, m-TOR inhibitors, and belatacept have shown more marginal impact on the GM. Most of these observations are descriptive. Future studies should explore the underlying mechanism of IST-induced dysbiosis in order to better understand their efficacy and safety characteristic
Preclinical Modeling of DCD class III Donation and Evaluation of the Most Adapted Preservation Protocol: Paving the Way for the Increased Use of this Challenging Donor Type
No full textInternational audienceCurrent organ shortage imposes the need to expand the donor pool. Deceased after circulatory death (DCD) donors are a promising source, and in particular the Maastricht class III (arrest subsequent to cessation of life support in the hospital). While current results from class III are positive, the unavoidable expansion of inclusion criteria will severely impact organ quality and increase the complication rate. It is thus of paramount importance to study this donor type in a controlled model in order to explore preservation protocols and be ready for future challenges. We endeavored to reproduce the clinical conditions of DCD class III in the Large White pig and used this novel model to compare the performances of machine and static preservation protocols. Through a combination of: -pharmacological calcium blockers and chronotropes; -decreased ventilation; and -animal positioning; we successfully reproduced the conditions of DCD class III in a large animal, obtaining perfusion pressures and functional warm ischemia (hypoperfusion) levels on par with situations encountered in the clinic. Important functional and histological impacts were recorded. Organs from these animals were then collected and preserved through 3 protocols for 24h: static preservation (University of Wisconsin), machine preservation (Lifeport), static (20h) combined to machine (4h). Isotransplanted animals were then followed for 3 months. Preliminary findings indicate that the level of damage withstood by the organs could not be compensated by machine perfusion alone. An extended analysis will be presented and exploration of alternative preservation protocols will be discussed. This model could be invaluable to investigate new management alternative for extended criteria class III DCD donors, such as normothermic regional circulation and/or pharmacological supplementation
Severe Strongyloidiasis in Solid Organ Transplant Recipients: Should We Preventively Treat the Recipient, the Donor, or Both?
No full textConcentration and chain length of polyethylene glycol in islet isolation solution: evaluation in a pancreatic islet transplantation model.
No full textInternational audienceTo improve graft preservation and consequently reduce conservation injuries, the composition of preservation solution is of outmost importance. It was demonstrated that the colloid polyethylene glycol (PEG), used in SCOT solution, has protective effects on cell membranes and immunocamouflage properties. The aim of this study was to optimize the concentration and chain length of PEG to improve pancreatic islet preservation and outcome. In a model of murine islet allotransplantation, islets were isolated with SCOT containing various concentrations of PEG 20 kDa or 35 kDa. Better islet yield (IEQ) was obtained with SCO +PEG at 15-30 g/L versus other PEG concentrations and control CMRL-1066 + 1% BSA solution (p < 0.05). Allograft survival was better prolonged (up to 20 days) in the groups SCOT + PEG 20 kDa 10-30 g/L compared to PEG 35 kDa (less than 17.8 days) and to control solutions (less than 17.5 days). In terms of graft function recovery, the use of PEG 20 kDa 15-30 g/L induced no primary nonfunction and delayed graft function contrary to CMRL-1066 and other PEG solutions. The use of the extracellular-type solution SCOT containing PEG 20 kDa 15 g/L as colloid could be a new way to optimize graft integrity preservation and allograft outcome
Severe Strongyloidiasis in Solid Organ Transplant Recipients: Should We Preventively Treat the Recipient, the Donor, or Both?
No full textInternational audienceStrongyloidiasis is caused by a soil-transmitted helminth that is endemic in tropical and subtropical countries. The parasite can complete its life cycle without leaving the host, allowing autoinfection and persistence. The risk of infection in travelers is low, but the disease may become lethal following immunosuppression. In case of solid organ transplantation, the risk of donor transmission has been suspected for several years. However, the management of live donors in this context has only recently been considered, and no guidelines exist for the management of deceased donors. To highlight the complexity of diagnosing, treating, and preventing strongyloidiasis donor transmission, we describe a case of possible transmission of severe strongyloidiasis to a kidney transplant recipient with limited travel history. Taking into account the difficulty of diagnosing chronic strongyloidiasis infection and the increase in travel and immunosuppressive treatments, we recommend pragmatic management guidelines to limit the risks of infection
Improving Long-Term Outcome in Allograft Transplantation: Role of Ionic Composition and Polyethylene Glycol
No full textInternational audienceBackground. Ischemia reperfusion injury (IRI) is inherent to transplantation, and correlates with negative outcome. Limiting IRI requires new preservation. Fourth generation solutions are emerging, using new colloid based on polyethylene glycol (PEG) polymers and extracellular ionic composition. We evaluated their eventual benefits for optimal resistance to IRI and improved outcome. Methods. Using primary cell culture and a preclinical pig model of low-mismatch kidney allograft transplantation, not requiring immunosuppression, we compared the following solutions: UW (University of Wisconsin), high potassium with hydroxyethyl starch, gold standard in preservation; IGL-1 (Institute George Lopez-1), low potassium solution using PEG (35 kDa, 1 g/L); and SCOT (Solution de Conservation des Organes et Tissus), plasma-like ionic composition, containing PEG 20 kDa (30 g/L). Results. In vitro, SCOT-preserved cells had better viability and less necrosis. In vivo, SCOT-grafts had better function recovery, with limited histological injury compared with the other solutions. During the 3 months follow-up, we found low innate and adaptative immune response in SCOT organs, whereas other groups presented high rate of invasion and antigen presentation. SCOT-preserved kidneys showed low fibrosis, transforming growth factor-beta expression and apoptosis compared with the other groups. These differences impacted survival at 3 months, which was low in UW (20%) and IGL-1 (40%) groups, whereas it remained high for SCOT animals (80%, P < 0.05 to UW). Conclusions. In conclusion, plasma-like ionic composition and nontoxic molecule PEG provide high resistance against IRI and optimize graft outcome. Such solutions could be invaluable for the use of fragile organs, such as from extended criteria or deceased after cardiac death donors
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