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      Normothermic Ex Vivo Kidney Perfusion for the Preservation of Kidney Grafts prior to Transplantation

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          Abstract

          Kidney transplantation has become a well-established treatment option for patients with end-stage renal failure. The persisting organ shortage remains a serious problem. Therefore, the acceptance criteria for organ donors have been extended leading to the usage of marginal kidney grafts. These marginal organs tolerate cold storage poorly resulting in increased preservation injury and higher rates of delayed graft function. To overcome the limitations of cold storage, extensive research is focused on alternative normothermic preservation methods.

          Ex vivo normothermic organ perfusion is an innovative preservation technique. The first experimental and clinical trials for ex vivo lung, liver, and kidney perfusions demonstrated favorable outcomes.

          In addition to the reduction of cold ischemic injury, the method of normothermic kidney storage offers the opportunity for organ assessment and repair. This manuscript provides information about kidney retrieval, organ preservation techniques, and isolated ex vivo normothermic kidney perfusion (NEVKP) in a porcine model. Surgical techniques, set up for the perfusion solution and the circuit, potential assessment options, and representative results are demonstrated.

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          Most cited references16

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          Normothermic ex vivo lung perfusion in clinical lung transplantation.

          More than 80% of donor lungs are potentially injured and therefore not considered suitable for transplantation. With the use of normothermic ex vivo lung perfusion (EVLP), the retrieved donor lung can be perfused in an ex vivo circuit, providing an opportunity to reassess its function before transplantation. In this study, we examined the feasibility of transplanting high-risk donor lungs that have undergone EVLP. In this prospective, nonrandomized clinical trial, we subjected lungs considered to be high risk for transplantation to 4 hours of EVLP. High-risk donor lungs were defined by specific criteria, including pulmonary edema and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PO(2):FIO(2)) less than 300 mm Hg. Lungs with acceptable function were subsequently transplanted. Lungs that were transplanted without EVLP during the same period were used as controls. The primary end point was primary graft dysfunction 72 hours after transplantation. Secondary end points were 30-day mortality, bronchial complications, duration of mechanical ventilation, and length of stay in the intensive care unit and hospital. During the study period, 136 lungs were transplanted. Lungs from 23 donors met the inclusion criteria for EVLP; in 20 of these lungs, physiological function remained stable during EVLP and the median PO(2):FIO(2) ratio increased from 335 mm Hg in the donor lung to 414 and 443 mm Hg at 1 hour and 4 hours of perfusion, respectively (P<0.001). These 20 lungs were transplanted; the other 116 lungs constituted the control group. The incidence of primary graft dysfunction 72 hours after transplantation was 15% in the EVLP group and 30% in the control group (P=0.11). No significant differences were observed for any secondary end points, and no severe adverse events were directly attributable to EVLP. Transplantation of high-risk donor lungs that were physiologically stable during 4 hours of ex vivo perfusion led to results similar to those obtained with conventionally selected lungs. (Funded by Vitrolife; ClinicalTrials.gov number, NCT01190059.).
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            Delayed graft function in kidney transplantation.

            Delayed graft function is a form of acute renal failure resulting in post-transplantation oliguria, increased allograft immunogenicity and risk of acute rejection episodes, and decreased long-term survival. Factors related to the donor and prerenal, renal, or postrenal transplant factors related to the recipient can contribute to this condition. From experimental studies, we have learnt that both ischaemia and reinstitution of blood flow in ischaemically damaged kidneys after hypothermic preservation activate a complex sequence of events that sustain renal injury and play a pivotal part in the development of delayed graft function. Elucidation of the pathophysiology of renal ischaemia and reperfusion injury has contributed to the development of strategies to decrease the rate of delayed graft function, focusing on donor management, organ procurement and preservation techniques, recipient fluid management, and pharmacological agents (vasodilators, antioxidants, anti-inflammatory agents). Several new drugs show promise in animal studies in preventing or ameliorating ischaemia-reperfusion injury and possibly delayed graft function, but definitive clinical trials are lacking. The goal of monotherapy for the prevention or treatment of is perhaps unattainable, and multidrug approaches or single drug targeting multiple signals will be the next step to reduce post-transplantation injury and delayed graft function.
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              Catheter replacement of the needle in percutaneous arteriography; a new technique.

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                Author and article information

                Journal
                J Vis Exp
                J Vis Exp
                JoVE
                Journal of Visualized Experiments : JoVE
                MyJove Corporation
                1940-087X
                2015
                15 July 2015
                15 July 2015
                : 101
                : 52909
                Affiliations
                1Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital
                2Division of Nephrology, The Hospital for Sick Children, Toronto
                3Department of General, Visceral & Transplant Surgery, University Medical Center Mainz
                4Department of Abdominal, Vascular & Transplant Surgery, Merheim Medical Center Cologne
                5Laboratory Medicine & Pathobiology, Toronto General Hospital
                6Departments of Surgery (Urology) & Physiology, The Hospital for Sick Children, Toronto
                7Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto
                Author notes

                Correspondence to: J. Moritz Kaths at moritz.kaths@ 123456gmail.com

                Article
                52909
                10.3791/52909
                4544894
                26275014
                9dc84b76-4f8e-4e0f-b057-4c502774e51e
                Copyright © 2015, Journal of Visualized Experiments

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial License, which permits non-commercial use, distribution, and reproduction, provided the original work is properly cited.

                History
                Categories
                Medicine

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                medicine,issue 101,kidney transplantation,organ shortage,organ preservation,normothermic ex vivo kidney perfusion (nevkp),cold storage (cs),hypothermic machine perfusion (hmp),standard criteria donor (scd),extended criteria donor (ecd),donation after circulatory death (dcd),marginal graft,delayed graft function (dgf),primary non function (pnf)

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