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1
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Pittappilly M, Sharshir M, Paramesh A. Chronic Allograft Nephropathy-A Narrative Review of Its Pathogenesis, Diagnosis, and Evolving Management Strategies. Biomedicines 2025; 13:929. [PMID: 40299546 PMCID: PMC12024747 DOI: 10.3390/biomedicines13040929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Revised: 03/29/2025] [Accepted: 04/03/2025] [Indexed: 04/30/2025] Open
Abstract
Chronic allograft nephropathy is the leading cause of kidney allograft failure. Clinically, it is characterized by a progressive decline in kidney function, often in combination with proteinuria and hypertension. Histologically, interstitial fibrosis and tubular atrophy, along with features of glomerulosclerosis with occasional double contour appearance, arteriolar hyalinosis, and arteriosclerosis, are characteristic findings. The pathophysiology, though complex and incompletely understood, is thought to involve a sequence of immunologic and non-immunologic injuries eventually leading to tissue remodeling and scarring within the graft. The optimal strategy to prevent chronic allograft nephropathy is to minimize both immune- and non-immune-mediated graft injury.
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Affiliation(s)
- Matthew Pittappilly
- Department of Nephrology, Tulane Transplant Institute, East Jefferson Hospital, Tulane University School of Medicine, New Orleans, LA 70112, USA; (M.P.); (M.S.)
| | - Mohammed Sharshir
- Department of Nephrology, Tulane Transplant Institute, East Jefferson Hospital, Tulane University School of Medicine, New Orleans, LA 70112, USA; (M.P.); (M.S.)
| | - Anil Paramesh
- Department of Surgery, Tulane Transplant Institute, East Jefferson Hospital, Tulane University School of Medicine, New Orleans, LA 70112, USA
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2
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Georgiou A, Tan W, Ionescu MI, Kuhn IL, Fritz Z. Ethical Issues in Uncontrolled Donation After Circulatory Determination of Death: A Scoping Review to Reveal Areas of Broad Consensus, and Those for Future Research. Transpl Int 2025; 38:13992. [PMID: 39981411 PMCID: PMC11840875 DOI: 10.3389/ti.2025.13992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Accepted: 01/17/2025] [Indexed: 02/22/2025]
Abstract
Uncontrolled donation after circulatory determination of death (uDCD) protocols are established in several countries with good outcomes. We reviewed the literature between 1997 and 2024 to identify ethical issues. 33 papers were identified. Several areas of continued ethical debate were delineated: the role of advanced life support techniques; the ethical acceptability of aortic occlusion balloons; the nature and timing of consent to organ preserving techniques; whether best interests can/should extend beyond individual bodily integrity in this context. Further empirical research and ethical analyses are needed in these domains. Broad consensus was identified on several issues including: decisions about termination of resuscitation and entry into a uDCD protocol should be made by different teams; at least 20-30 min of cardio-pulmonary resuscitation is required; a hands-off period of 5-7 min is required alongside continuous monitoring; organ preserving techniques should be as minimally invasive as possible; families should be approached early to discuss organ donation by trained staff; public knowledge and engagement about uDCD is poor and must be improved; transparency and informed consent are essential for potential uDCD organ recipients. To maintain transparency and encourage positive public engagement we propose a name change from uDCD to Organ Donation after Sudden Irreversible Cardiac Arrest (ODASICA).
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Affiliation(s)
- Anastasia Georgiou
- School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Weiyi Tan
- School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Mihnea I. Ionescu
- Miami Transplant Institute, Jackson Health System, Miami, FL, United States
| | - Isla L. Kuhn
- THIS (The Healthcare Improvement Studies) Institute, University of Cambridge, Cambridge, United Kingdom
| | - Zoe Fritz
- THIS (The Healthcare Improvement Studies) Institute, University of Cambridge, Cambridge, United Kingdom
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3
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Pionnier Y, Darius T, Penaloza A, Steenebruggen F, Dupriez F, Neyrinck A, Genbrugge C. Solid organ transplantation originating from uncontrolled donation after circulatory death in Europe: a narrative review. Scand J Trauma Resusc Emerg Med 2024; 32:130. [PMID: 39695729 PMCID: PMC11654252 DOI: 10.1186/s13049-024-01305-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 12/04/2024] [Indexed: 12/20/2024] Open
Abstract
Human organ transplantation has begun in the 1960s with donation after circulatory death. At that time this was named non heart beating donation, later donation after cardiac death and nowadays it is named donation after circulatory death. Currently, we are facing a significant shortage of transplant organs in Europe and worldwide. To increase the graft acceptance from donation after controlled or uncontrolled circulatory death, preceding regional normothermic perfusion by an extracorporeal circulation before organ procurement or ex-situ machine perfusion are frequently implemented in clinical practice as organ assessment and reconditioning techniques. Due to these advancements more organs can be potentially transplanted, even after out-of-hospital cardiac arrest (OHCA). First line actors like emergency physicians and pre-hospital paramedics must be aware of such programs to recognize and refer patients for donation in OHCA situations. This review provides an overview of organs transplanted from uncontrolled donation after circulatory death (uDCD) and emphasize the role of the emergency physician in the organ donation cascade. Outcome of uDCD has a lower effectiveness than donation after brain death (DBD) and controlled donation after circulatory death (cDCD) for short term graft survival. However, observational studies illustrate that long term outcome from uDCD is comparable to graft outcome from cDCD and DBD. We summarize the studies reporting the procured organ rate and functional outcome of organs originated from uDCD. European databases indicate a high incidence of OHCA, where resuscitation efforts are initiated but the rate of return of spontaneous circulation (ROSC) remains limited. These patients represent a substantial potential pool of organ donors for uDCD programs. However, these programs tend to overestimate the number of potential donors. While organ procurement from uDCD has yielded favorable outcomes, further research is required to accurately assess the associated costs and benefits and to establish clear donor selection guidelines. Furthermore, the use of new technologies like extracorporeal Cardiopulmonary Resuscitation (E-CPR) for organ donation should be investigated from both medical and economical perspectives. Emergency departments must also explore the feasibility of implementing these programs.
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Affiliation(s)
- Yann Pionnier
- Emergency Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
| | - Tom Darius
- Department of Abdominal Surgery and Transplantation, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Andrea Penaloza
- Emergency Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | | | - Florence Dupriez
- Emergency Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Arne Neyrinck
- Department of Anesthesiology, University Hospitals Leuven, Louvain, Belgium
| | - Cornelia Genbrugge
- Emergency Department, Cliniques Universitaires Saint-Luc, Emergency Medicine, Department of Public Health and Primary Care, Faculty of Medicine, Catholic University Leuven, Brussels, Belgium
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4
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Hasjim BJ, Sanders JM, Alexander M, Redfield RR, Ichii H. Perfusion Techniques in Kidney Allograft Preservation to Reduce Ischemic Reperfusion Injury: A Systematic Review and Meta-Analysis. Antioxidants (Basel) 2024; 13:642. [PMID: 38929081 PMCID: PMC11200710 DOI: 10.3390/antiox13060642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 05/16/2024] [Accepted: 05/20/2024] [Indexed: 06/28/2024] Open
Abstract
The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative stress to expand the donor pool. Organ preservation and procurement techniques, such as machine perfusion (MP) and normothermic regional perfusion (NRP), have been developed to preserve allograft function, though their long-term outcomes have been more challenging to investigate. We performed a systematic review and meta-analysis to examine the benefits of MP and NRP compared to traditional preservation techniques. PubMed (MEDLINE), Embase, Cochrane, and Scopus databases were queried, and of 13,794 articles identified, 54 manuscripts were included (n = 41 MP; n = 13 NRP). MP decreased the rates of 12-month graft failure (OR 0.67; 95%CI 0.55, 0.80) and other perioperative outcomes such as delayed graft function (OR 0.65; 95%CI 0.54, 0.79), primary nonfunction (OR 0.63; 95%CI 0.44, 0.90), and hospital length of stay (15.5 days vs. 18.4 days) compared to static cold storage. NRP reduced the rates of acute rejection (OR 0.48; 95%CI 0.35, 0.67) compared to in situ perfusion. Overall, MP and NRP are effective techniques to mitigate IRI and play an important role in safely expanding the donor pool to satisfy the increasing demands of kidney transplantation.
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Affiliation(s)
- Bima J. Hasjim
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery and Islet Cell Transplantation, University of California–Irvine, Orange, CA 92868, USA; (B.J.H.); (M.A.)
| | - Jes M. Sanders
- Department of Surgery, Division of Transplantation, Northwestern Memorial Hospital, Chicago, IL 60611, USA;
| | - Michael Alexander
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery and Islet Cell Transplantation, University of California–Irvine, Orange, CA 92868, USA; (B.J.H.); (M.A.)
| | - Robert R. Redfield
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery and Islet Cell Transplantation, University of California–Irvine, Orange, CA 92868, USA; (B.J.H.); (M.A.)
| | - Hirohito Ichii
- Department of Surgery, Division of Hepatobiliary and Pancreas Surgery and Islet Cell Transplantation, University of California–Irvine, Orange, CA 92868, USA; (B.J.H.); (M.A.)
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5
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Nagaraju S, Savilla R, Moore M, Jones A, Africa J. Successful transplantation of LUCAS device assisted uncontrolled DCD kidneys with prolonged relative warm ischemia time: An underutilized option in North America. Clin Transplant 2023; 37:e15058. [PMID: 37421597 DOI: 10.1111/ctr.15058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 04/27/2023] [Accepted: 06/11/2023] [Indexed: 07/10/2023]
Abstract
Approximately 25% of deceased donors in the United States are procured in a donation after circulatory death (DCD) setting. Successful transplant outcomes from uncontrolled DCD (uDCD) practices have been reported in multiple European programs. They utilize established protocols for uDCD procurement with normo-thermic or hypothermic regional perfusion to reduce ischemic damage. Further, manual or mechanical chest compressions using extrinsic devices, such as the LUCAS device, are implemented to maintain circulation before organ retrieval. Currently, uDCDs are not a major part of DCD organ utilization in the United States. We report our experience with utilization of kidneys from uDCD with the use of the LUCAS device without normothermic or hypothermic regional perfusion. We transplanted four kidneys from three uDCD donors without utilization of in situ regional perfusion and with prolonged relative warm ischemia time (rWIT) (>100 min). All recipients had functional renal allografts and improved renal function after the transplant. To our knowledge, this is the 1st successful series reported in the United States of the utilization of kidneys from uDCDs without the utilization of in situ perfusion to maintain organ preservation with prolonged rWIT.
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Affiliation(s)
- Santosh Nagaraju
- Renal Transplant Program, Charleston Area Medical Center, Charleston, West Virginia, USA
| | - Rachel Savilla
- Renal Transplant Program, Charleston Area Medical Center, Charleston, West Virginia, USA
| | - Myla Moore
- Renal Transplant Program, Charleston Area Medical Center, Charleston, West Virginia, USA
| | - Alice Jones
- Renal Transplant Program, Charleston Area Medical Center, Charleston, West Virginia, USA
| | - Joseph Africa
- Renal Transplant Program, Charleston Area Medical Center, Charleston, West Virginia, USA
- Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA
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6
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Ghoneima AS, Sousa Da Silva RX, Gosteli MA, Barlow AD, Kron P. Outcomes of Kidney Perfusion Techniques in Transplantation from Deceased Donors: A Systematic Review and Meta-Analysis. J Clin Med 2023; 12:3871. [PMID: 37373568 DOI: 10.3390/jcm12123871] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 05/03/2023] [Accepted: 05/09/2023] [Indexed: 06/29/2023] Open
Abstract
The high demand for organs in kidney transplantation and the expansion of the donor pool have led to the widespread implementation of machine perfusion technologies. In this study, we aim to provide an up-to-date systematic review of the developments in this expanding field over the past 10 years, with the aim of answering the question: "which perfusion technique is the most promising technique in kidney transplantation?" A systematic review of the literature related to machine perfusion in kidney transplantation was performed. The primary outcome measure was delayed graft function (DGF), and secondary outcomes included rates of rejection, graft survival, and patient survival rates after 1 year. Based on the available data, a meta-analysis was performed. The results were compared with data from static cold storage, which is still the standard of care in many centers worldwide. A total of 56 studies conducted in humans were included, and 43 studies reported outcomes of hypothermic machine perfusion (HMP), with a DGF rate of 26.4%. A meta-analysis of 16 studies showed significantly lower DGF rates in the HMP group compared to those of static cold storage (SCS). Five studies reported outcomes of hypothermic machine perfusion + O2, with an overall DGF rate of 29.7%. Two studies explored normothermic machine perfusion (NMP). These were pilot studies, designed to assess the feasibility of this perfusion approach in the clinical setting. Six studies reported outcomes of normothermic regional perfusion (NRP). The overall incidence of DGF was 71.5%, as it was primarily used in uncontrolled DCD (Maastricht category I-II). Three studies comparing NRP to in situ cold perfusion showed a significantly lower rate of DGF with NRP. The systematic review and meta-analysis provide evidence that dynamic preservation strategies can improve outcomes following kidney transplantation. More recent approaches such as normothermic machine perfusion and hypothermic machine perfusion + O2 do show promising results but need further results from the clinical setting. This study shows that the implementation of perfusion strategies could play an important role in safely expanding the donor pool.
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Affiliation(s)
- Ahmed S Ghoneima
- Department of HPB and Transplant Surgery, St. James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds LS9 7TF, UK
| | - Richard X Sousa Da Silva
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zurich, 8091 Zurich, Switzerland
| | | | - Adam D Barlow
- Department of HPB and Transplant Surgery, St. James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds LS9 7TF, UK
| | - Philipp Kron
- Department of HPB and Transplant Surgery, St. James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds LS9 7TF, UK
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zurich, 8091 Zurich, Switzerland
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7
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Farinelli P, Juri J, Varela D, Salome M, Bisigniano L, Raimondi C, Magnate AD, Barone ME, Fernandez MF, Cambariere R, Villavicencio S, Pregno E, Klein F, Villamil A, Schelotto PB, Gondolesi GE. Donation after Cardiocirculatory Death: a program that we must implement. Experts Argentinean meeting report. TRANSPLANTATION REPORTS 2023. [DOI: 10.1016/j.tpr.2023.100132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2023] Open
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8
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Li Marzi V, Pecoraro A, Gallo ML, Caroti L, Peris A, Vignolini G, Serni S, Campi R. Robot-assisted kidney transplantation: Is it getting ready for prime time? World J Transplant 2022; 12:163-174. [PMID: 36051450 PMCID: PMC9331411 DOI: 10.5500/wjt.v12.i7.163] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 03/08/2022] [Accepted: 06/17/2022] [Indexed: 02/06/2023] Open
Abstract
Kidney transplantation (KT) is the treatment of choice for patients with end-stage renal disease, providing a better survival rate and quality of life compared to dialysis. Despite the progress in the medical management of KT patients, from a purely surgical standpoint, KT has resisted innovations during the last 50 years. Recently, robot-assisted KT (RAKT) has been proposed as an alternative approach to open surgery, especially due to its potential benefits for fragile and immunocompromised recipients. It was not until 2014 that the role of RAKT has found value thanks to the pioneering Vattikuti Urology Institute-Medanta collaboration that conceptualized and developed a new surgical technique for RAKT following the Idea, Development, Exploration, Assessment, Long-term follow-up recommendations for introducing surgical innovations into real-life practice. During the last years, mirroring the Vattikuti-Medanta technique, several centers developed RAKT program worldwide, providing strong evidence about the safety and the feasibility of this procedure. However, the majority of RAKT are still performed in the living donor setting, as an “eligible” procedure, while only a few centers have realized KT through a robotic approach in the challenging scenario of cadaver donation. In addition, despite the spread of minimally-invasive (predominantly robotic) surgery worldwide, many KTs are still performed in an open fashion. Regardless of the type of incision employed by surgeons, open KT may lead to non-negligible risks of wound complications, especially among obese patients. Particularly, the assessment for KT should consider not only the added surgical technical challenges but also the higher risk of postoperative complications. In this context, robotic surgery could offer several benefits, including providing a better exposure of the surgical field and better instrument maneuverability, as well as the possibility to integrate other technological nuances, such as the use of intraoperative fluorescence vascular imaging with indocyanine green to assess the ureteral vascularization before the uretero-vesical anastomosis. Therefore, our review aims to report the more significant experiences regarding RAKT, focusing on the results and future perspectives.
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Affiliation(s)
- Vincenzo Li Marzi
- Department of Minimally Invasive and Robotic Urologic Surgery, Careggi University Hospital, University of Florence, Florence 50134, Italy
| | - Alessio Pecoraro
- Department of Minimally Invasive and Robotic Urologic Surgery, Careggi University Hospital, University of Florence, Florence 50134, Italy
| | - Maria Lucia Gallo
- Department of Minimally Invasive and Robotic Urologic Surgery, Careggi University Hospital, University of Florence, Florence 50134, Italy
| | | | - Adriano Peris
- Intensive Care Unit and Regional ECMO Referral Centre, Careggi Hospital, Florence 50134, Italy
| | - Graziano Vignolini
- Department of Minimally Invasive and Robotic Urologic Surgery, Careggi University Hospital, University of Florence, Florence 50134, Italy
| | - Sergio Serni
- Department of Minimally Invasive and Robotic Urologic Surgery, University of Florence, Florence 50134, Italy
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Riccardo Campi
- Department of Minimally Invasive and Robotic Urologic Surgery, Careggi University Hospital, University of Florence, Florence 50134, Italy
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
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9
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De Beule J, Vandendriessche K, Pengel LHM, Bellini MI, Dark JH, Hessheimer AJ, Kimenai HJAN, Knight SR, Neyrinck AP, Paredes D, Watson CJE, Rega F, Jochmans I. A systematic review and meta-analyses of regional perfusion in donation after circulatory death solid organ transplantation. Transpl Int 2021; 34:2046-2060. [PMID: 34570380 DOI: 10.1111/tri.14121] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 09/16/2021] [Accepted: 09/20/2021] [Indexed: 12/29/2022]
Abstract
In donation after circulatory death (DCD), (thoraco)abdominal regional perfusion (RP) restores circulation to a region of the body following death declaration. We systematically reviewed outcomes of solid organ transplantation after RP by searching PubMed, Embase, and Cochrane libraries. Eighty-eight articles reporting on outcomes of liver, kidney, pancreas, heart, and lung transplants or donor/organ utilization were identified. Meta-analyses were conducted when possible. Methodological quality was assessed using National Institutes of Health (NIH)-scoring tools. Case reports (13/88), case series (44/88), retrospective cohort studies (35/88), retrospective matched cohort studies (5/88), and case-control studies (2/88) were identified, with overall fair quality. As blood viscosity and rheology change below 20 °C, studies were grouped as hypothermic (HRP, ≤20 °C) or normothermic (NRP, >20 °C) regional perfusion. Data demonstrate that RP is a safe alternative to in situ cold preservation (ISP) in uncontrolled and controlled DCDs. The scarce HRP data are from before 2005. NRP appears to reduce post-transplant complications, especially biliary complications in controlled DCD livers, compared with ISP. Comparisons for kidney and pancreas with ISP are needed but there is no evidence that NRP is detrimental. Additional data on NRP in thoracic organs are needed. Whether RP increases donor or organ utilization needs further research.
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Affiliation(s)
- Julie De Beule
- Transplantation Research Group, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium
| | | | - Liset H M Pengel
- Nuffield Department of Surgical Sciences, Centre for Evidence in Transplantation, University of Oxford, Oxford, UK
| | - Maria Irene Bellini
- Department of Emergency Medicine and Surgery, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
| | - John H Dark
- Faculty of Medical Sciences, Translational and Clinical Research Institute, Newcastle University, Newcastle, UK
| | - Amelia J Hessheimer
- Department of General & Digestive Surgery, Institut Clínic de Malalties Digestives i Metabòliques (ICMDM), Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | - Hendrikus J A N Kimenai
- Division of Transplant Surgery, Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Simon R Knight
- Nuffield Department of Surgical Sciences, Centre for Evidence in Transplantation, University of Oxford, Oxford, UK.,Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Arne P Neyrinck
- Department of Cardiovascular Sciences, Anesthesiology and Algology, KU Leuven, Leuven, Belgium.,Department of Anesthesiology, University Hospitals Leuven, Leuven, Belgium
| | - David Paredes
- Donation and Transplant Coordination Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Christopher J E Watson
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.,The NIHR Cambridge Biomedical Research Centre, Cambridge, UK
| | - Filip Rega
- Department of Cardiovascular Sciences, Cardiac Surgery, KU Leuven, Leuven, Belgium.,Department of Cardiac Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Ina Jochmans
- Transplantation Research Group, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
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10
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Artiles Medina A, Burgos Revilla FJ, Álvarez Nadal M, Muriel García A, Álvarez Díaz N, Gómez Dos Santos V. Comparison of in situ preservation techniques for kidneys from donors after circulatory death: a systematic review and meta-analysis. Transl Androl Urol 2021; 10:3286-3299. [PMID: 34532253 PMCID: PMC8421834 DOI: 10.21037/tau-21-236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 06/11/2021] [Indexed: 11/06/2022] Open
Abstract
Background Several techniques have been developed to reduce the warm ischaemic injury of donation after circulatory death (DCD) organs before procurement. There are scarce data about the in situ preservation techniques for kidney graft outcomes. The aim of this systematic review was to evaluate the best in situ preservation method for kidney graft outcomes from organs obtained from controlled and uncontrolled DCD. Methods A systematic review of the PubMed (MEDLINE), Embase, LILACS and Cochrane databases was conducted. Studies that compare two or more in situ preservation techniques were identified and included. Only studies which provided enough data to calculate odds ratio were eligible for meta-analysis. PROSPERO registration: CRD42020179598. Results The search strategy yielded 7,121 studies. Ultimately, 14 retrospective studies were included. Because of heterogeneity, the included studies provided weak evidence that normothermic regional perfusion (NRP) is the best in situ preservation technique in terms of delayed graft function (DGF) rates. Regarding primary nonfunction (PNF), we carried out a meta-analysis of 10 studies with a pooled OR of 0.83 (95% CI: 0.40-1.71), for the NRP. In regard to DGF, pooled OR for NRP was 0.36 (95% CI: 0.25-0.54). Conclusions NRP in the DCD donor could improve kidney graft function and be considered the in situ preservation technique of choice for abdominal organs.
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Affiliation(s)
- Alberto Artiles Medina
- Department of Urology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - Francisco Javier Burgos Revilla
- Department of Urology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - Marta Álvarez Nadal
- Department of Nephrology, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Alfonso Muriel García
- Department of Biostatistics, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), CIBERESP, Universidad de Alcalá de Henares (UAH), Madrid, Spain
| | | | - Victoria Gómez Dos Santos
- Department of Urology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
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11
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van de Leemkolk FEM, Schurink IJ, Dekkers OM, Oniscu GC, Alwayn IPJ, Ploeg RJ, de Jonge J, Huurman VAL. Abdominal Normothermic Regional Perfusion in Donation After Circulatory Death: A Systematic Review and Critical Appraisal. Transplantation 2020; 104:1776-1791. [PMID: 32541563 DOI: 10.1097/tp.0000000000003345] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Abdominal normothermic regional perfusion (aNRP) for donation after circulatory death is an emerging organ preservation technique that might lead to increased organ utilization per donor by facilitating viability testing, improving transplant outcome by early reversal of ischemia, and decreasing the risk of unintentional surgical damage. The aim of the current review is to evaluate the recent literature on the added value of aNRP when compared to local standard perfusion technique. METHODS The Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline for systematic reviews was used, and relevant literature databases were searched. Primary outcomes were organ utilization rate and patient and graft survival after 1 year. Secondary outcomes included delayed graft function, primary nonfunction, serum creatinine, and biliary complications. RESULTS A total of 24 articles were included in this review. The technique is unanimously reported to be feasible and safe, but the available studies are characterized by considerable heterogeneity and bias. CONCLUSIONS Uniform reported outcome measures are needed to draw more definitive conclusions on transplant outcomes and organ utilization. A randomized controlled trial comparing aNRP with standard procurement technique in donation after circulatory death donors would be needed to show the added value of the procedure and determine its place among modern preservation techniques.
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Affiliation(s)
- Fenna E M van de Leemkolk
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
- LUMC Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Ivo J Schurink
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Olaf M Dekkers
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Gabriel C Oniscu
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
| | - Ian P J Alwayn
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
- LUMC Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Rutger J Ploeg
- LUMC Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Volkert A L Huurman
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
- LUMC Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
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Coll E, Miñambres E, Sánchez-Fructuoso A, Fondevila C, Campo-Cañaveral de la Cruz JL, Domínguez-Gil B. Uncontrolled Donation After Circulatory Death: A Unique Opportunity. Transplantation 2020; 104:1542-1552. [PMID: 32732830 DOI: 10.1097/tp.0000000000003139] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Uncontrolled donation after circulatory death (uDCD) refers to donation from persons who die following an unexpected and unsuccessfully resuscitated cardiac arrest. Despite the large potential for uDCD, programs of this kind only exist in a reduced number of countries with a limited activity. Barriers to uDCD are of a logistical and ethical-legal nature, as well as arising from the lack of confidence in the results of transplants from uDCD donors. The procedure needs to be designed to reduce and limit the impact of the prolonged warm ischemia inherent to the uDCD process, and to deal with the ethical issues that this practice poses: termination of advanced cardiopulmonary resuscitation, extension of advanced cardiopulmonary resuscitation beyond futility for organ preservation, moment to approach families to discuss donation opportunities, criteria for the determination of death, or the use of normothermic regional perfusion for the in situ preservation of organs. Although the incidence of primary nonfunction and delayed graft function is higher with organs obtained from uDCD donors, overall patient and graft survival is acceptable in kidney, liver, and lung transplantation, with a proper selection and management of both donors and recipients. Normothermic regional perfusion has shown to be critical to achieve optimal outcomes in uDCD kidney and liver transplantation. However, the role of ex situ preservation with machine perfusion is still to be elucidated. uDCD is a unique opportunity to improve patient access to transplantation therapies and to offer more patients the chance to donate organs after death, if this is consistent with their wishes and values.
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Affiliation(s)
| | - Eduardo Miñambres
- Intensive Care Unit and Donor Coordination Unit, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Spain
| | - Ana Sánchez-Fructuoso
- Nephrology Department, Hospital Universitario Clínico San Carlos, Facultad de Medicina, Universidad Complutense, Madrid, Spain
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Choudhury RA, Prins K, Dor Y, Moore HB, Yaffe H, Nydam TL. Uncontrolled donation after circulatory death improves access to kidney transplantation: A decision analysis. Clin Transplant 2020; 34:e13868. [PMID: 32259310 DOI: 10.1111/ctr.13868] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 03/06/2020] [Accepted: 03/27/2020] [Indexed: 02/06/2023]
Abstract
AIM Uncontrolled donation after cardiac death (uDCD) remains an underutilized source of kidney allografts in the United States. The objective of this study was to estimate the impact of the implementation of a uDCD program on transplantation rates and long-term survival for patients with end-stage renal disease (ESRD) in the United States. METHODS A decision-analytic Markov state transition model was created using medical decision-making software (DATA 3.5; TreeAge Software, Inc) to estimate the impact of an uDCD program on transplantation rates and patient survival. Additionally, sensitivity analysis of uDCD donor pool increase was modeled. All model statistic parameters were extracted from the literature. RESULTS A uDCD program increased the rate of transplant at 10 years (37.8%, Accept uDCD group, vs 35.9%, Reject uDCD group). At 10 years, overall survival for Accept uDCD was 55.6% compared to 54.8% in the Reject uDCD. CONCLUSIONS Uncontrolled DCD improves access to transplant for ESRD patients on the kidney transplant waitlist, thereby improving long-term survival.
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Affiliation(s)
- Rashikh A Choudhury
- Department of Surgery, Division of Transplantation Surgery, University of Colorado Hospital, Aurora, CO, USA
| | - Kas Prins
- Department of Surgery, Division of Transplantation Surgery, University of Colorado Hospital, Aurora, CO, USA
| | - Yoeli Dor
- Department of Surgery, Division of Transplantation Surgery, University of Colorado Hospital, Aurora, CO, USA
| | - Hunter B Moore
- Department of Surgery, Division of Transplantation Surgery, University of Colorado Hospital, Aurora, CO, USA
| | - Hillary Yaffe
- Department of Surgery, Division of Transplantation Surgery, University of Colorado Hospital, Aurora, CO, USA
| | - Trevor L Nydam
- Department of Surgery, Division of Transplantation Surgery, University of Colorado Hospital, Aurora, CO, USA
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15
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Potential Applications of Extracellular Vesicles in Solid Organ Transplantation. Cells 2020; 9:cells9020369. [PMID: 32033489 PMCID: PMC7072603 DOI: 10.3390/cells9020369] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 01/30/2020] [Accepted: 02/05/2020] [Indexed: 12/14/2022] Open
Abstract
Extracellular vesicles (EVs) play an important role in cell-to-cell communication by delivering coding and non-coding RNA species and proteins to target cells. Recently, the therapeutic potential of EVs has been shown to extend to the field of solid organ transplantations. Mesenchymal stromal cell-derived EVs (MSC-EVs) in particular have been proposed as a new tool to improve graft survival, thanks to the modulation of tolerance toward the graft, and to their anti-fibrotic and pro-angiogenic effects. Moreover, MSC-EVs may reduce ischemia reperfusion injury, improving the recovery from acute damage. In addition, EVs currently considered helpful tools for preserving donor organs when administered before transplant in the context of hypothermic or normothermic perfusion machines. The addition of EVs to the perfusion solution, recently proposed for kidney, lung, and liver grafts, resulted in the amelioration of donor organ viability and functionality. EVs may therefore be of therapeutic interest in different aspects of the transplantation process for increasing the number of available organs and improving their long-term survival.
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Georgiades F, Hosgood SA, Butler AJ, Nicholson ML. Use of ex vivo normothermic machine perfusion after normothermic regional perfusion to salvage a poorly perfused DCD kidney. Am J Transplant 2019; 19:3415-3419. [PMID: 31355509 DOI: 10.1111/ajt.15547] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 07/07/2019] [Accepted: 07/23/2019] [Indexed: 02/06/2023]
Abstract
Normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) have both been used in the procurement and conditioning of abdominal organs from donation after circulatory death donors with reported improved outcomes for the recipients. Here, we describe an unusual case of a kidney that underwent NMP after NRP. After 2 hours of abdominal NRP, the intra-abdominal organs were cold flushed in situ. The liver and right kidney were well flushed, but the left kidney was poorly flushed. Further attempts to clear the left kidney by flushing on the backtable were unsuccessful, and the kidney was thought to be unsuitable for transplant. The left kidney then underwent a 1-hour period of NMP using a red cell-based perfusate. During NMP, the kidney met previously described quality assurance criteria for transplant with good global perfusion and adequate renal blood flow and urine production. The kidney was transplanted into a suitable recipient who had slow early graft function but did not require dialysis posttransplant. The recipient was discharged 6 days posttransplant, and the serum creatinine level was 160 μmol/L (1.8 mg/dL) at 2 months posttransplant.
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Affiliation(s)
- Fanourios Georgiades
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
| | - Sarah A Hosgood
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
| | - Andrew J Butler
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
| | - Michael L Nicholson
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
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Lomero M, Gardiner D, Coll E, Haase‐Kromwijk B, Procaccio F, Immer F, Gabbasova L, Antoine C, Jushinskis J, Lynch N, Foss S, Bolotinha C, Ashkenazi T, Colenbie L, Zuckermann A, Adamec M, Czerwiński J, Karčiauskaitė S, Ström H, López‐Fraga M, Dominguez‐Gil B, Sarkissian A, Liashchuk S, Tsvetkova E, Bušić M, Michael N, Ilkjaer LB, Dmitriev P, Makisalo H, Rahmel A, Tomadze G, Ioannis B, Mihály S, Carella C, Codreanu I, Jansen N, Konijn C, França A, Zota V, Žilinská Z, Avsec D, Gautier S, Sánchez‐Ibáñez J, Terrón C, Vidal C, Beyeler F, Weiss J, Ilbars T, Forsythe J, Johnson R, Enckevort A. Donation after circulatory death today: an updated overview of the European landscape. Transpl Int 2019; 33:76-88. [DOI: 10.1111/tri.13506] [Citation(s) in RCA: 98] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 05/28/2019] [Accepted: 08/26/2019] [Indexed: 01/03/2023]
Affiliation(s)
- Mar Lomero
- European Directorate for the Quality of Medicines & Healthcare/Council of Europe Strasbourg France
| | - Dale Gardiner
- National Clinical Lead for Organ Donation NHS Blood and Transplant Watford UK
| | | | | | - Francesco Procaccio
- Italian National Transplant Centre Italian National Institute of Health Rome Italy
| | - Franz Immer
- Swisstransplant The Swiss National Foundation for Organ Donation and Transplantation Bern Switzerland
| | - Lyalya Gabbasova
- Ministry of Health of the Russian Federation Moscow Russian Federation
| | | | | | - Nessa Lynch
- Organ Donation Transplant Ireland Dublin Ireland
| | | | - Catarina Bolotinha
- National Transplantation Coordination Instituto Português do Sangue e da Transplantação Lisboa Portugal
| | - Tamar Ashkenazi
- Israel Transplant Center State of Israel Ministry of Health Tel‐Aviv Israel
| | - Luc Colenbie
- DG Health Care Organs Embryo's and Bio‐Ethics Brussels Belgium
| | | | - Miloš Adamec
- Koordinační Středisko Transplantací Prague Czech Republic
| | | | - Sonata Karčiauskaitė
- National Transplant Bureau Under the Ministry of Health of the Republic Lithuania Vilnius Lithuania
| | - Helena Ström
- Department for Knowledge‐Based Policy of Health Care National Donation Centre Stockholm Sweden
| | - Marta López‐Fraga
- European Directorate for the Quality of Medicines & Healthcare/Council of Europe Strasbourg France
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Organ donation after circulatory death: current status and future potential. Intensive Care Med 2019; 45:310-321. [DOI: 10.1007/s00134-019-05533-0] [Citation(s) in RCA: 108] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Accepted: 01/14/2019] [Indexed: 01/26/2023]
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Hadj‐Moussa H, Storey KB. Bringing nature back: using hibernation to reboot organ preservation. FEBS J 2018; 286:1094-1100. [DOI: 10.1111/febs.14683] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 09/14/2018] [Accepted: 10/17/2018] [Indexed: 12/19/2022]
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Roncon-Albuquerque R, Gaião S, Figueiredo P, Príncipe N, Basílio C, Mergulhão P, Silva S, Honrado T, Cruz F, Pestana M, Oliveira G, Meira L, França A, Almeida-Sousa JP, Araújo F, Paiva JA. An integrated program of extracorporeal membrane oxygenation (ECMO) assisted cardiopulmonary resuscitation and uncontrolled donation after circulatory determination of death in refractory cardiac arrest. Resuscitation 2018; 133:88-94. [PMID: 30321624 DOI: 10.1016/j.resuscitation.2018.10.016] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 10/10/2018] [Accepted: 10/11/2018] [Indexed: 10/28/2022]
Abstract
AIM To assess the feasibility of an integrated program of extracorporeal cardiopulmonary resuscitation (ECPR) and uncontrolled donation after circulatory determination of death (uDCDD) in refractory cardiac arrest (rCA). METHODS Single center, prospective, observational study of selected patients with in-hospital (IHCA) and out-of-hospital (OHCA) rCA occurring in an urban area of ∼1.5 million inhabitants, between October-2016 and May-2018. 65 year old or younger patients without significant bleeding or comorbidities with witnessed nonasystolic cardiac arrests were triaged to ECPR if they had a reversible cause and high quality CPR lasting < 60 min. Otherwise they were considered for uDCDD after a ten minute no touch period using normothermic regional perfusion. RESULTS 58 patients were included, of which 41 (71%) were OHCA and 18 (31%) had ECPR initiated. Median age was 52 (IQR 45-56) years. Cannulation was successful in 49/58 (84%) cases. Compared to ECPR, patients referred for uDCDD were more frequently OHCA (90 vs. 28%), had bystander CPR (28 vs. 83%) and prolonged low-flow period (40 (35-50) vs. 60 (49-78) min). Survival to hospital discharge with full neurological recovery (cerebral performance category 1) occurred in 6/18 (33%) ECPR patients. uDCDD resulted in transplantation of 44 kidneys. CONCLUSIONS An integrated program for rCA consisting of a formal pathway to uDCDD referral in ECPR ineligible patients is feasible. ECPR-referred patients had a reasonable survival with full neurologic recovery. Successful kidney transplantation was achieved with uDCDD.
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Affiliation(s)
- Roberto Roncon-Albuquerque
- Department of Emergency and Intensive Care Medicine, São João Hospital Centre, Porto, Portugal; Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Portugal.
| | - Sérgio Gaião
- Department of Emergency and Intensive Care Medicine, São João Hospital Centre, Porto, Portugal; Department of Medicine, Faculty of Medicine, University of Porto, Portugal
| | - Paulo Figueiredo
- Department of Infectious Diseases, São João Hospital Centre, Porto, Portugal
| | - Nuno Príncipe
- Department of Emergency and Intensive Care Medicine, São João Hospital Centre, Porto, Portugal
| | - Carla Basílio
- Department of Emergency and Intensive Care Medicine, São João Hospital Centre, Porto, Portugal
| | - Paulo Mergulhão
- Department of Emergency and Intensive Care Medicine, São João Hospital Centre, Porto, Portugal; Department of Medicine, Faculty of Medicine, University of Porto, Portugal
| | - Sofia Silva
- Department of Emergency and Intensive Care Medicine, São João Hospital Centre, Porto, Portugal
| | - Teresa Honrado
- Department of Emergency and Intensive Care Medicine, São João Hospital Centre, Porto, Portugal
| | - Francisco Cruz
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Portugal; Department of Urology, São João Hospital Centre, Porto, Portugal; i3S: Instituto de Investigação e Inovação em Saúde, Portugal
| | - Manuel Pestana
- Department of Medicine, Faculty of Medicine, University of Porto, Portugal; Department of Nephrology, São João Hospital Centre, Porto, Portugal; Nephrology and Infectious Diseases R&D Group, Instituto de Investigação e Inovação em Saúde (INEB-i3S), Universidade do Porto, Portugal
| | - Gerardo Oliveira
- Department of Medicine, Faculty of Medicine, University of Porto, Portugal; Organ Donation and Transplant Coordination Office, São João Hospital Centre, Porto, Portugal
| | - Luis Meira
- National Institute of Medical Emergency, Portugal
| | - Ana França
- Portuguese Institute for Blood and Transplantation, Portugal
| | | | | | - José-Artur Paiva
- Department of Emergency and Intensive Care Medicine, São João Hospital Centre, Porto, Portugal; Department of Medicine, Faculty of Medicine, University of Porto, Portugal
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