Combined Flush With Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Solutions in Liver Transplantation: Preliminary Results

Díaz, F.; Aguilar, José Luis Fernández; Cabo, Sara Nicolás de; Reyes, María Pérez; Pérez, Belinda Sánchez; Casado, Custodia Montiel; Daga, J.A. Pérez; Narváez, José Manuel Aranda; Muñóz, Miguel Ángel Suárez; González, F A; Rías, M.M. Florez; Angulo, Juanita; Santoyo, Julio Santoyo

doi:10.1016/j.transproceed.2017.12.033

Cited by 6 publications

(3 citation statements)

References 12 publications

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“…The advantages of these storage solutions include improved preservation of the kidney, heart, and liver, while the disadvantages include higher occurrence of HTK-associated biliary complications. The UW solution may increase the risk of graft non-function [4]. With an increased demand for surgery, organ shortage has led to the use of extended criteria for liver donation [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

et al. 2020

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Background: Donation after circulatory death (DCD) liver grafts have a poor prognosis after transplantation. We investigated whether the outcome of DCD donor organs can be improved by heme oxygenase 1 (HO-1)-modified bone marrow-derived mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP), and explored its underlying mechanisms. Methods: BMMSCs were isolated, cultured, and transduced with the HO-1 gene. An NMP system was established. DCD rat livers were obtained, preserved by different methods, and the recipients were divided into 5 groups: sham operation, static cold storage (SCS), NMP, BMMSCs combined with NMP, and HO-1/BMMSCs combined with NMP (HBP) groups. Rats were sacrificed at 1, 7, and 14 days after surgery; their blood and liver tissue samples were collected; and liver enzyme and cytokine levels, liver histology, high-mobility group box 1 (HMGB1) levels in monocytes and liver tissues, and expression of Toll-like receptor 4 (TLR4) pathway-related molecules were evaluated. Results: After liver transplantation, the SCS group showed significantly increased transaminase levels, liver tissue damage, and shorter survival time. The HBP group showed lower transaminase levels, intact liver morphology, prolonged survival time, and decreased serum and liver proinflammatory cytokine levels. In the NMP and SCS groups, HMGB1 expression in the serum, monocytes, and liver tissues and TLR4 pathway-related molecule expression were significantly decreased. Conclusions: HO-1/BMMSCs combined with NMP exerted protective effects on DCD donor liver and significantly improved recipient prognosis. The effect of HO-1/BMMSCs was greater than that of BMMSCs and was mediated via HMGB1 expression and TLR4 pathway inhibition.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

et al. 2020

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“…These interventions include procedures at organ recovery (eg, preservation solution, normothermic regional perfusion), ex situ treatments (eg, pulsatile machine perfusion, ex vivo lung perfusion) and post-transplant therapies (eg, nitric oxide, mannitol). [21][22][23][24][25][26][27] However, interventions administered directly to the donor provide an opportunity to precondition organs against IRI.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

Calcineurin Inhibitor in NEuRoloGically deceased donors to decrease kidney delayed graft function study: study protocol of the CINERGY Pilot randomised controlled trial

D'Aragon,

Selzner,

Breau

et al. 2024

BMJ Open

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IntroductionMost solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk.Methods and analysisWe designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation.Ethics and disseminationWe will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309).Trial registration numberNCT05148715.

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“…5,6 Interventions that attenuate IRI can improve graft viability. Clinical trials support many of these interventions, including specific operative procedures at the time of organ procurement (eg, preservation solution, normothermic regional perfusion), 7,8 ex situ treatments (eg, pulsatile machine perfusion, ex vivo lung perfusion), [9][10][11] and posttransplant therapies (nitric oxide, mannitol). 12,13 However, interventions directed specifically to the donor provide a unique opportunity to precondition organs against IRI.…”

Section: Introductionmentioning

confidence: 99%

Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies

D’Aragon,

Rousseau,

Breau

et al. 2023

Transplantation Direct

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Background. Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia–reperfusion injury to improve transplant outcomes. Methods. We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively. Results. Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47). Conclusions. Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application.

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Combined Flush With Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Solutions in Liver Transplantation: Preliminary Results

Cited by 6 publications

References 12 publications

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

Calcineurin Inhibitor in NEuRoloGically deceased donors to decrease kidney delayed graft function study: study protocol of the CINERGY Pilot randomised controlled trial

Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies

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