Effect of N-Acetylcysteine Pretreatment of Deceased Organ Donors on Renal Allograft Function

Orban, Jean-Christophe; Quintard, Hervé; Cassuto, Élisabeth; Jambou, P.; Samat-Long, Corine; Ichai, Carole

doi:10.1097/tp.0000000000000395

Cited by 38 publications

(31 citation statements)

References 44 publications

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“…Recently, an open‐label monocentre trial with 160 DBDs failed to show a beneficial effect of N‐acetylcysteine pretreatment. N‐acetylcysteine neither affected incidence or duration of DGF nor one‐year graft survival .…”

Section: Management Strategies Prior To Organ Retrievalmentioning

confidence: 79%

Optimized donor management and organ preservation before kidney transplantation

et al. 2015

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SUMMARYKidney transplantation is a major medical improvement for patients with end-stage renal disease, but organ shortage limits its widespread use. As a consequence, the proportion of grafts procured from extended criteria donors (ECD) has increased considerably, but this comes along with increased rates of delayed graft function (DGF) and a higher incidence of immune-mediated rejection that limits organ and patient survival. Furthermore, most grafts are derived from brain dead organ donors, but the unphysiological state of brain death is associated with significant metabolic, hemodynamic, and pro-inflammatory changes, which further compromise patient and graft survival. Thus, donor interventions to preserve graft quality are fundamental to improve long-term transplantation outcome, but interventions must not harm other potentially transplantable grafts. Several donor pretreatment strategies have provided encouraging results in animal models, but evidence from human studies is sparse, as most clinical evidence is derived from single-center or nonrandomized trials. Furthermore, ethical matters have to be considered especially concerning consent from donors, donor families, and transplant recipients to research in the field of donor treatment. This review provides an overview of clinically proven and promising preclinical strategies of donor treatment to optimize long-term results after kidney transplantation. Transplant International 2016; 29: 974-984

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Section: Management Strategies Prior To Organ Retrievalmentioning

confidence: 79%

Optimized donor management and organ preservation before kidney transplantation

et al. 2015

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“…It seems that reperfusion induces sustained abnormalities leading to tissue damage characterized by apoptotic and necrotic cell death and finally renal dysfunction. To our knowledge, several clinical interventions aiming to decrease such damages have reported conflicting results on the incidence of DGF [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of cyclosporine A pretreatment of deceased organ donors on kidney graft function (Cis-A-rein): study protocol for a randomized controlled trial

Orban

Fontaine

Cassuto

et al. 2018

Trials

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BackgroundRenal transplantation represents the treatment of choice of end-stage kidney disease. Delayed graft function (DGF) remains the most frequent complication after this procedure, reaching more than 30%. Its prevention is essential as it impedes early- and long-term prognosis of transplantation. Numerous pharmacological interventions aiming to prevent ischemia-reperfusion injuries failed to reduce the rate of DGF. We hypothesize that cyclosporine as an early preconditioning procedure in donors would be associated with decreased DGF.MethodsThe Cis-A-rein study is an investigator-initiated, prospective, multicenter, double-blind, randomized, controlled study performed to assess the effects of a donor preconditioning with cyclosporine A on kidney grafts function in transplanted patients. After randomization, a brain dead donor will receive 2.5 mg kg−1 of cyclosporine A or the same volume of 5% glucose solution. The primary objective is to compare the rate of DGF, defined as the need for at least one dialysis session within the 7 days following transplantation, between both groups. The secondary objectives include rate of slow graft function, mild and severe DGF, urine output and serum creatinine during the first week after transplantation, rate of primary graft dysfunction, renal function and mortality at 1 year. The sample size (n = 648) was determined to obtain 80% power to detect a 10% difference for rate of DGF at day 7 between the two groups (30% of the patients in the placebo group and 20% of the patients in the intervention group).DiscussionDelayed graft function is a major issue after renal transplantation, impeding long-term prognosis. Cyclosporine A pretreatment in deceased donors could improve the outcome of patients after renal transplantation.Trial registrationClinicalTrials.gov, ID: NCT02907554 Registered on 20 September 2016. Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2597-4) contains supplementary material, which is available to authorized users.

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“…The antioxidative treatment approach with the aim of scavenging ROS, which increase during brain death and IRI, was also addressed in the clinical setting; however, they could not show an improvement of survival in LT and kidney transplantation [55,56,57,58], though short-term liver function was shown to be improved by the application of ascorbic acid and donor ventilation with sevoflurane. Sevoflurane was also reported by Minou et al [58] to be protective in steatotic livers.…”

Section: Approaches For Preconditioning Organs In Order To Improve Trmentioning

confidence: 99%

Control of Ischemia-Reperfusion Injury in Liver Transplantation: Potentials for Increasing the Donor Pool

Kahn

Schemmer

2018

Visc Med

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Background: Organ shortage is a growing problem, with a rising number of organs being harvested from extended criteria donors, and this trend will further continue to increase as organ donors are getting older and have more comorbidities. Since this fact is immutable, efforts have been made to reduce the extent of ischemia-reperfusion injury (IRI) as well as of direct and indirect harvest-related graft injury which affects all organs in a more or less distinct way. Methods: In liver transplantation (LT), the activation of Kupffer cells during organ reperfusion, thus provoking microcirculatory disturbances, hypoxia, and endothelial cell injury, is one of the key mechanisms causing graft dysfunction. Multiple approaches have been taken in order to find efficient preconditioning methods by pharmacological pretreatment, controlled induction of ischemia, controlled denervation of donor organs, and reconditioning with machine perfusion to prevent IRI, whereas marginal organs (i.e. steatotic grafts) are especially vulnerable. Results: The above-mentioned approaches have been pursued in experimental and clinical settings. At this time point, however, there is not yet enough clinical evidence available to recommend any particular drug pretreatment or any other intervention for organ preconditioning prior to transplantation. Conclusion: The multifactorial pathophysiology in the setting of IRI in LT requires a multimodal therapeutic approach with the integration of pharmacological and technical means being applied to the donor, the organ per se, and the recipient. Currently, there is no consensus on standardized pretreatment of donor organs in order to improve the transplant outcome.

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Effect of N-Acetylcysteine Pretreatment of Deceased Organ Donors on Renal Allograft Function

Cited by 38 publications

References 44 publications

Optimized donor management and organ preservation before kidney transplantation

Optimized donor management and organ preservation before kidney transplantation

Effects of cyclosporine A pretreatment of deceased organ donors on kidney graft function (Cis-A-rein): study protocol for a randomized controlled trial

Control of Ischemia-Reperfusion Injury in Liver Transplantation: Potentials for Increasing the Donor Pool

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