The Experts below are selected from a list of 5370 Experts worldwide ranked by ideXlab platform
Thierry Hauet - One of the best experts on this subject based on the ideXlab platform.
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In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion
International Journal of Molecular Sciences, 2020Co-Authors: Sébastien Giraud, Raphaël Thuillier, Jérome Cau, Thierry HauetAbstract:Oxidative stress is a key element of ischemia–reperfusion injury, occurring during Kidney Preservation and transplantation. Current options for Kidney graft Preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of Preservation quality, particularly for marginal donors, such as extended criteria donors (ECDs) and donation after circulatory death (DCDs). Nevertheless, complications still exist, fostering the need to improve Kidney Preservation. This review highlights the most promising avenues of in Kidney perfusion improvement on two critical aspects: ex vivo and in vitro evaluation.
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New strategies to optimize Kidney recovery and Preservation in transplantation
Nature reviews. Nephrology, 2012Co-Authors: Delphine Bon, Frédéric Favreau, Nicolas Chatauret, Raphaël Thuillier, Sébastien Giraud, Thierry HauetAbstract:Optimizing Kidney Preservation is a primary concern in transplantation, particularly in relation to new donor sources, such as expanded criteria donors and donation after cardiac death. Here, the authors describe emerging strategies to prevent ischemia–reperfusion injuries in donor Kidneys and describe innovative interventions at the donor, graft Preservation or recipient levels to improve recovery, evaluation and outcome of Kidney grafts.
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New strategies to optimize Kidney recovery and Preservation in transplantation
Nature Reviews Nephrology, 2012Co-Authors: Delphine Bon, Frédéric Favreau, Nicolas Chatauret, Raphaël Thuillier, Sébastien Giraud, Thierry HauetAbstract:Optimizing Kidney Preservation is a primary issue in transplantation, particularly in relation to new donor sources, such as expanded criteria donors (ECDs) and donation after cardiac death (DCD). Kidneys from these donors are highly sensitive to ischemia-reperfusion injuries--the emblematic lesions encountered during transplantation. Despite years of research, static cold storage, with solutions designed in the 1980s, remains the gold standard in Kidney transplantation. This kind of Preservation, however, is unable to fully protect an ECD or DCD Kidney, highlighting the need for novel strategies to improve Kidney Preservation or promote Kidney recovery. This Review provides an overview of the emerging strategies to prevent ischemia-reperfusion injuries in donor Kidneys and describes strategies that are aimed at the donor, organ or recipient to improve graft outcome. These approaches include management of donors, preconditioning of the Kidney, improvements in organ Preservation solutions, postconditioning and regenerative therapies of the Kidney graft following transplantation. In addition, machine perfusion provides an interesting opportunity to evaluate Kidney graft quality before transplantation. Overall, a combination of therapeutic approaches seem to provide the best outcome, but preclinical studies using relevant models are needed before these approaches can be incorporated into clinical practice.
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Evaluation of pulsatile perfusion machine RM3 for Kidney Preservation in a swine model of renal autotransplantation
Transplantation Proceedings, 2009Co-Authors: Ricardo Codas, Lionel Badet, Raphaël Thuillier, M. Eugene, S. Giraud, Thierry HauetAbstract:Transplantations of Kidneys from non–heart-beating donors (NHBD) are intended to increase the donor pool by 20% to 30%. Nevertheless the rate of primary nonfunction and delayed graft function is generally higher among this group of donors. The goal of this study was to assess whether Kidney Preservation by a pulsatile perfusion machine was able to limit the renal lesions due to ischemia reperfusion injuries as compared with static incubation. We have used a model of an autotransplanted Kidney exposed to controlled warm ischemia in the pig to mimic the clinical conditions of NHBD.
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Evaluation of pulsatile perfusion machine RM3 for Kidney Preservation in a swine model of renal autotransplantation.
Transplantation proceedings, 2009Co-Authors: Ricardo Codas, Lionel Badet, Sébastien Giraud, Michel Eugene, R. Thuiller, Thierry HauetAbstract:Abstract Aim Transplantations of Kidneys from non–heart-beating donors (NHBD) are intended to increase the donor pool by 20% to 30%. Nevertheless the rate of primary nonfunction and delayed graft function is generally higher among this group of donors. The goal of this study was to assess whether Kidney Preservation by a pulsatile perfusion machine was able to limit the renal lesions due to ischemia reperfusion injuries as compared with static incubation. We have used a model of an autotransplanted Kidney exposed to controlled warm ischemia in the pig to mimic the clinical conditions of NHBD. Material and Methods Left Kidneys from 11 large white pigs aged 4 weeks were harvested after vascular clamping of the renal vessels for 1 hour. Kidneys were preserved for 22 hours. Two groups were studied: the MPS static group (static incubation with Belzer MPS; n = 6) versus the MPS RM group (renal perfusion with Belzer MPS; n = 5). Kidneys were then autotransplanted into pigs after a right nephrectomy. The primary end point was animal survival rate at 1 month. Secondary endpoints were evolution of the plasma creatinine values, proteinuria, tubular sodium reabsorption, and histological features at 1 month. Results For all biological parameters, the differences between the perfusion and the static incubation groups were significant, except creatinine, with favorable effects for the perfusion machine group. The histological data at 1 month showed recovery of the normal Kidney architecture in the MPS RM group. Conclusion In our pig experimental model that reproduced the clinical conditions of a NHBD, we demonstrated better Kidney Preservation when the pulsatile perfusion machine was used as compared with static conservation.
Sébastien Giraud - One of the best experts on this subject based on the ideXlab platform.
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In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion
International Journal of Molecular Sciences, 2020Co-Authors: Sébastien Giraud, Raphaël Thuillier, Jérome Cau, Thierry HauetAbstract:Oxidative stress is a key element of ischemia–reperfusion injury, occurring during Kidney Preservation and transplantation. Current options for Kidney graft Preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of Preservation quality, particularly for marginal donors, such as extended criteria donors (ECDs) and donation after circulatory death (DCDs). Nevertheless, complications still exist, fostering the need to improve Kidney Preservation. This review highlights the most promising avenues of in Kidney perfusion improvement on two critical aspects: ex vivo and in vitro evaluation.
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Barriers and Advances in Kidney Preservation
BioMed research international, 2018Co-Authors: Clara Steichen, Lionel Badet, Delphine Bon, Sébastien Giraud, Benoit Barrou, E. Salame, Thomas Kerforne, Géraldine Allain, Jerome Roumy, Christophe JayleAbstract:Despite the fact that a significant fraction of Kidney graft dysfunctions observed after transplantation is due to ischemia-reperfusion injuries, there is still no clear consensus regarding optimal Kidney Preservation strategy. This stems directly from the fact that as of yet, the mechanisms underlying ischemia-reperfusion injury are poorly defined, and the role of each Preservation parameter is not clearly outlined. In the meantime, as donor demography changes, organ quality is decreasing which directly increases the rate of poor outcome. This situation has an impact on clinical guidelines and impedes their possible harmonization in the transplant community, which has to move towards changing organ Preservation paradigms: new concepts must emerge and the definition of a new range of adapted Preservation method is of paramount importance. This review presents existing barriers in transplantation (e.g., temperature adjustment and adequate protocol, interest for oxygen addition during Preservation, and clear procedure for organ perfusion during machine Preservation), discusses the development of novel strategies to overcome them, and exposes the importance of identifying reliable biomarkers to monitor graft quality and predict short and long-term outcomes. Finally, perspectives in therapeutic strategies will also be presented, such as those based on stem cells and their derivatives and innovative models on which they would need to be properly tested.
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The Optimal PEG for Kidney Preservation: A Preclinical Porcine Study
International Journal of Molecular Sciences, 2018Co-Authors: Sébastien Giraud, Emily Manguy, Alexandre Valagier, Alexis Puichaud, Lionel Badet, Emmanuelle Nicolas, Raphaël Thuillier, Benoit Barrou, Ricardo Codas, Michel EugeneAbstract:University of Wisconsin (UW) solution is not optimal for Preservation of marginal organs. Polyethylene glycol (PEG) could improve protection. Similarly formulated solutions containing either 15 or 20 g/L PEG 20 kDa or 5, 15 and 30 g/L PEG 35 kDa were tested in vitro on Kidney endothelial cells, ex vivo on preserved Kidneys, and in vivo in a pig Kidney autograft model. In vitro, all PEGs provided superior Preservation than UW in terms of cell survival, adenosine triphosphate (ATP) production, and activation of survival pathways. Ex vivo, tissue injury was lower with PEG 20 kDa compared to UW or PEG 35 kDa. In vivo, function recovery was identical between UW and PEG 35 kDa groups, while PEG 20 kDa displayed swifter recovery. At three months, PEG 35 kDa 15 and 30 g/L animals had worse outcomes than UW, while 5 g/L PEG 35 kDa was similar. PEG 20 kDa was superior to both UW and PEG 35 kDa in terms of function and fibrosis development, with low activation of damage pathways. PEG 20 kDa at 15 g/L was superior to 20 g/L. While in vitro models did not discriminate between PEGs, in large animal models of transplantation we showed that PEG 20 kDa offers a higher level of protection than UW and that longer chains such as PEG 35 kDa must be used at low doses, such as found in Institut George Lopez (IGL1, 1g/L).
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New strategies to optimize Kidney recovery and Preservation in transplantation
Nature reviews. Nephrology, 2012Co-Authors: Delphine Bon, Frédéric Favreau, Nicolas Chatauret, Raphaël Thuillier, Sébastien Giraud, Thierry HauetAbstract:Optimizing Kidney Preservation is a primary concern in transplantation, particularly in relation to new donor sources, such as expanded criteria donors and donation after cardiac death. Here, the authors describe emerging strategies to prevent ischemia–reperfusion injuries in donor Kidneys and describe innovative interventions at the donor, graft Preservation or recipient levels to improve recovery, evaluation and outcome of Kidney grafts.
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New strategies to optimize Kidney recovery and Preservation in transplantation
Nature Reviews Nephrology, 2012Co-Authors: Delphine Bon, Frédéric Favreau, Nicolas Chatauret, Raphaël Thuillier, Sébastien Giraud, Thierry HauetAbstract:Optimizing Kidney Preservation is a primary issue in transplantation, particularly in relation to new donor sources, such as expanded criteria donors (ECDs) and donation after cardiac death (DCD). Kidneys from these donors are highly sensitive to ischemia-reperfusion injuries--the emblematic lesions encountered during transplantation. Despite years of research, static cold storage, with solutions designed in the 1980s, remains the gold standard in Kidney transplantation. This kind of Preservation, however, is unable to fully protect an ECD or DCD Kidney, highlighting the need for novel strategies to improve Kidney Preservation or promote Kidney recovery. This Review provides an overview of the emerging strategies to prevent ischemia-reperfusion injuries in donor Kidneys and describes strategies that are aimed at the donor, organ or recipient to improve graft outcome. These approaches include management of donors, preconditioning of the Kidney, improvements in organ Preservation solutions, postconditioning and regenerative therapies of the Kidney graft following transplantation. In addition, machine perfusion provides an interesting opportunity to evaluate Kidney graft quality before transplantation. Overall, a combination of therapeutic approaches seem to provide the best outcome, but preclinical studies using relevant models are needed before these approaches can be incorporated into clinical practice.
Raphaël Thuillier - One of the best experts on this subject based on the ideXlab platform.
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In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion
International Journal of Molecular Sciences, 2020Co-Authors: Sébastien Giraud, Raphaël Thuillier, Jérome Cau, Thierry HauetAbstract:Oxidative stress is a key element of ischemia–reperfusion injury, occurring during Kidney Preservation and transplantation. Current options for Kidney graft Preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of Preservation quality, particularly for marginal donors, such as extended criteria donors (ECDs) and donation after circulatory death (DCDs). Nevertheless, complications still exist, fostering the need to improve Kidney Preservation. This review highlights the most promising avenues of in Kidney perfusion improvement on two critical aspects: ex vivo and in vitro evaluation.
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The Optimal PEG for Kidney Preservation: A Preclinical Porcine Study
International Journal of Molecular Sciences, 2018Co-Authors: Sébastien Giraud, Emily Manguy, Alexandre Valagier, Alexis Puichaud, Lionel Badet, Emmanuelle Nicolas, Raphaël Thuillier, Benoit Barrou, Ricardo Codas, Michel EugeneAbstract:University of Wisconsin (UW) solution is not optimal for Preservation of marginal organs. Polyethylene glycol (PEG) could improve protection. Similarly formulated solutions containing either 15 or 20 g/L PEG 20 kDa or 5, 15 and 30 g/L PEG 35 kDa were tested in vitro on Kidney endothelial cells, ex vivo on preserved Kidneys, and in vivo in a pig Kidney autograft model. In vitro, all PEGs provided superior Preservation than UW in terms of cell survival, adenosine triphosphate (ATP) production, and activation of survival pathways. Ex vivo, tissue injury was lower with PEG 20 kDa compared to UW or PEG 35 kDa. In vivo, function recovery was identical between UW and PEG 35 kDa groups, while PEG 20 kDa displayed swifter recovery. At three months, PEG 35 kDa 15 and 30 g/L animals had worse outcomes than UW, while 5 g/L PEG 35 kDa was similar. PEG 20 kDa was superior to both UW and PEG 35 kDa in terms of function and fibrosis development, with low activation of damage pathways. PEG 20 kDa at 15 g/L was superior to 20 g/L. While in vitro models did not discriminate between PEGs, in large animal models of transplantation we showed that PEG 20 kDa offers a higher level of protection than UW and that longer chains such as PEG 35 kDa must be used at low doses, such as found in Institut George Lopez (IGL1, 1g/L).
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New strategies to optimize Kidney recovery and Preservation in transplantation
Nature reviews. Nephrology, 2012Co-Authors: Delphine Bon, Frédéric Favreau, Nicolas Chatauret, Raphaël Thuillier, Sébastien Giraud, Thierry HauetAbstract:Optimizing Kidney Preservation is a primary concern in transplantation, particularly in relation to new donor sources, such as expanded criteria donors and donation after cardiac death. Here, the authors describe emerging strategies to prevent ischemia–reperfusion injuries in donor Kidneys and describe innovative interventions at the donor, graft Preservation or recipient levels to improve recovery, evaluation and outcome of Kidney grafts.
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New strategies to optimize Kidney recovery and Preservation in transplantation
Nature Reviews Nephrology, 2012Co-Authors: Delphine Bon, Frédéric Favreau, Nicolas Chatauret, Raphaël Thuillier, Sébastien Giraud, Thierry HauetAbstract:Optimizing Kidney Preservation is a primary issue in transplantation, particularly in relation to new donor sources, such as expanded criteria donors (ECDs) and donation after cardiac death (DCD). Kidneys from these donors are highly sensitive to ischemia-reperfusion injuries--the emblematic lesions encountered during transplantation. Despite years of research, static cold storage, with solutions designed in the 1980s, remains the gold standard in Kidney transplantation. This kind of Preservation, however, is unable to fully protect an ECD or DCD Kidney, highlighting the need for novel strategies to improve Kidney Preservation or promote Kidney recovery. This Review provides an overview of the emerging strategies to prevent ischemia-reperfusion injuries in donor Kidneys and describes strategies that are aimed at the donor, organ or recipient to improve graft outcome. These approaches include management of donors, preconditioning of the Kidney, improvements in organ Preservation solutions, postconditioning and regenerative therapies of the Kidney graft following transplantation. In addition, machine perfusion provides an interesting opportunity to evaluate Kidney graft quality before transplantation. Overall, a combination of therapeutic approaches seem to provide the best outcome, but preclinical studies using relevant models are needed before these approaches can be incorporated into clinical practice.
-
Evaluation of pulsatile perfusion machine RM3 for Kidney Preservation in a swine model of renal autotransplantation
Transplantation Proceedings, 2009Co-Authors: Ricardo Codas, Lionel Badet, Raphaël Thuillier, M. Eugene, S. Giraud, Thierry HauetAbstract:Transplantations of Kidneys from non–heart-beating donors (NHBD) are intended to increase the donor pool by 20% to 30%. Nevertheless the rate of primary nonfunction and delayed graft function is generally higher among this group of donors. The goal of this study was to assess whether Kidney Preservation by a pulsatile perfusion machine was able to limit the renal lesions due to ischemia reperfusion injuries as compared with static incubation. We have used a model of an autotransplanted Kidney exposed to controlled warm ischemia in the pig to mimic the clinical conditions of NHBD.
Delphine Bon - One of the best experts on this subject based on the ideXlab platform.
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Barriers and Advances in Kidney Preservation
BioMed research international, 2018Co-Authors: Clara Steichen, Lionel Badet, Delphine Bon, Sébastien Giraud, Benoit Barrou, E. Salame, Thomas Kerforne, Géraldine Allain, Jerome Roumy, Christophe JayleAbstract:Despite the fact that a significant fraction of Kidney graft dysfunctions observed after transplantation is due to ischemia-reperfusion injuries, there is still no clear consensus regarding optimal Kidney Preservation strategy. This stems directly from the fact that as of yet, the mechanisms underlying ischemia-reperfusion injury are poorly defined, and the role of each Preservation parameter is not clearly outlined. In the meantime, as donor demography changes, organ quality is decreasing which directly increases the rate of poor outcome. This situation has an impact on clinical guidelines and impedes their possible harmonization in the transplant community, which has to move towards changing organ Preservation paradigms: new concepts must emerge and the definition of a new range of adapted Preservation method is of paramount importance. This review presents existing barriers in transplantation (e.g., temperature adjustment and adequate protocol, interest for oxygen addition during Preservation, and clear procedure for organ perfusion during machine Preservation), discusses the development of novel strategies to overcome them, and exposes the importance of identifying reliable biomarkers to monitor graft quality and predict short and long-term outcomes. Finally, perspectives in therapeutic strategies will also be presented, such as those based on stem cells and their derivatives and innovative models on which they would need to be properly tested.
-
New strategies to optimize Kidney recovery and Preservation in transplantation
Nature reviews. Nephrology, 2012Co-Authors: Delphine Bon, Frédéric Favreau, Nicolas Chatauret, Raphaël Thuillier, Sébastien Giraud, Thierry HauetAbstract:Optimizing Kidney Preservation is a primary concern in transplantation, particularly in relation to new donor sources, such as expanded criteria donors and donation after cardiac death. Here, the authors describe emerging strategies to prevent ischemia–reperfusion injuries in donor Kidneys and describe innovative interventions at the donor, graft Preservation or recipient levels to improve recovery, evaluation and outcome of Kidney grafts.
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New strategies to optimize Kidney recovery and Preservation in transplantation
Nature Reviews Nephrology, 2012Co-Authors: Delphine Bon, Frédéric Favreau, Nicolas Chatauret, Raphaël Thuillier, Sébastien Giraud, Thierry HauetAbstract:Optimizing Kidney Preservation is a primary issue in transplantation, particularly in relation to new donor sources, such as expanded criteria donors (ECDs) and donation after cardiac death (DCD). Kidneys from these donors are highly sensitive to ischemia-reperfusion injuries--the emblematic lesions encountered during transplantation. Despite years of research, static cold storage, with solutions designed in the 1980s, remains the gold standard in Kidney transplantation. This kind of Preservation, however, is unable to fully protect an ECD or DCD Kidney, highlighting the need for novel strategies to improve Kidney Preservation or promote Kidney recovery. This Review provides an overview of the emerging strategies to prevent ischemia-reperfusion injuries in donor Kidneys and describes strategies that are aimed at the donor, organ or recipient to improve graft outcome. These approaches include management of donors, preconditioning of the Kidney, improvements in organ Preservation solutions, postconditioning and regenerative therapies of the Kidney graft following transplantation. In addition, machine perfusion provides an interesting opportunity to evaluate Kidney graft quality before transplantation. Overall, a combination of therapeutic approaches seem to provide the best outcome, but preclinical studies using relevant models are needed before these approaches can be incorporated into clinical practice.
Michel Eugene - One of the best experts on this subject based on the ideXlab platform.
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The Optimal PEG for Kidney Preservation: A Preclinical Porcine Study
International Journal of Molecular Sciences, 2018Co-Authors: Sébastien Giraud, Emily Manguy, Alexandre Valagier, Alexis Puichaud, Lionel Badet, Emmanuelle Nicolas, Raphaël Thuillier, Benoit Barrou, Ricardo Codas, Michel EugeneAbstract:University of Wisconsin (UW) solution is not optimal for Preservation of marginal organs. Polyethylene glycol (PEG) could improve protection. Similarly formulated solutions containing either 15 or 20 g/L PEG 20 kDa or 5, 15 and 30 g/L PEG 35 kDa were tested in vitro on Kidney endothelial cells, ex vivo on preserved Kidneys, and in vivo in a pig Kidney autograft model. In vitro, all PEGs provided superior Preservation than UW in terms of cell survival, adenosine triphosphate (ATP) production, and activation of survival pathways. Ex vivo, tissue injury was lower with PEG 20 kDa compared to UW or PEG 35 kDa. In vivo, function recovery was identical between UW and PEG 35 kDa groups, while PEG 20 kDa displayed swifter recovery. At three months, PEG 35 kDa 15 and 30 g/L animals had worse outcomes than UW, while 5 g/L PEG 35 kDa was similar. PEG 20 kDa was superior to both UW and PEG 35 kDa in terms of function and fibrosis development, with low activation of damage pathways. PEG 20 kDa at 15 g/L was superior to 20 g/L. While in vitro models did not discriminate between PEGs, in large animal models of transplantation we showed that PEG 20 kDa offers a higher level of protection than UW and that longer chains such as PEG 35 kDa must be used at low doses, such as found in Institut George Lopez (IGL1, 1g/L).
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Evaluation of pulsatile perfusion machine RM3 for Kidney Preservation in a swine model of renal autotransplantation.
Transplantation proceedings, 2009Co-Authors: Ricardo Codas, Lionel Badet, Sébastien Giraud, Michel Eugene, R. Thuiller, Thierry HauetAbstract:Abstract Aim Transplantations of Kidneys from non–heart-beating donors (NHBD) are intended to increase the donor pool by 20% to 30%. Nevertheless the rate of primary nonfunction and delayed graft function is generally higher among this group of donors. The goal of this study was to assess whether Kidney Preservation by a pulsatile perfusion machine was able to limit the renal lesions due to ischemia reperfusion injuries as compared with static incubation. We have used a model of an autotransplanted Kidney exposed to controlled warm ischemia in the pig to mimic the clinical conditions of NHBD. Material and Methods Left Kidneys from 11 large white pigs aged 4 weeks were harvested after vascular clamping of the renal vessels for 1 hour. Kidneys were preserved for 22 hours. Two groups were studied: the MPS static group (static incubation with Belzer MPS; n = 6) versus the MPS RM group (renal perfusion with Belzer MPS; n = 5). Kidneys were then autotransplanted into pigs after a right nephrectomy. The primary end point was animal survival rate at 1 month. Secondary endpoints were evolution of the plasma creatinine values, proteinuria, tubular sodium reabsorption, and histological features at 1 month. Results For all biological parameters, the differences between the perfusion and the static incubation groups were significant, except creatinine, with favorable effects for the perfusion machine group. The histological data at 1 month showed recovery of the normal Kidney architecture in the MPS RM group. Conclusion In our pig experimental model that reproduced the clinical conditions of a NHBD, we demonstrated better Kidney Preservation when the pulsatile perfusion machine was used as compared with static conservation.
