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Werenski H, Stratta RJ, Sharda B, Garner M, Farney AC, Orlando G, McCracken E, Jay CL. Knowing When to Ignore the Numbers: Single-Center Experience Transplanting Deceased Donor Kidneys with Poor Perfusion Parameters. J Am Coll Surg 2023; 236:848-857. [PMID: 36735482 DOI: 10.1097/xcs.0000000000000611] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Hypothermic machine perfusion is frequently used in evaluating marginal kidneys with poor perfusion parameters (PPP) contributing to delays in kidney placement or discard. We examined outcomes in deceased donor kidney transplants with PPP compared with those with optimal perfusion parameters (OPP). STUDY DESIGN We conducted a retrospective single-center cohort study from 2001 to 2021 comparing PPP (n = 91) with OPP (n = 598) deceased donor kidney transplants. PPP was defined as terminal flow ≤80 mL/min and terminal resistance ≥0.40 mmHg/mL/min. OPP was defined as terminal flow ≥120 mL/min and terminal resistance ≤0.20 mmHg/mL/min. RESULTS Mean terminal flow was PPP 66 ± 16 vs OPP 149 ± 21 mL/min and resistance was PPP 0.47 ± 0.10 vs OPP 0.15 ± 0.04 mmHg/mL/min (both p < 0.001). Donor age, donation after cardiac death, and terminal serum creatinine levels were similar between groups. Mean Kidney Donor Profile Index was higher among PPP donors (PPP 65 ± 23% vs OPP 52 ± 27%, p < 0.001). The PPP transplant group had more females and lower weight and BMI. Delayed graft function was comparable (PPP 32% vs OPP 27%, p = 0.33) even though cold ischemia times trended toward longer in PPP kidneys (PPP 28 ± 10 vs OPP 26 ± 9 hours, p = 0.09). One-year patient survival (PPP 98% vs OPP 97%, p = 0.84) and graft survival (PPP 91% vs OPP 92%, p = 0.23) were equivalent. PPP did predict inferior overall and death-censored graft survival long-term (overall hazard ratio 1.63, 95% CI 1.19 to 2.23 and death-censored hazard ratio 1.77, 95% CI 1.15 to 2.74). At 1 year, the estimated glomerular filtration rate was higher with OPP kidneys (PPP 40 ± 17 vs OPP 52 ± 19 mL/min/1.73 m 2 , p < 0.001). CONCLUSIONS Short-term outcomes in PPP kidneys were comparable to OPP kidneys despite higher Kidney Donor Profile Index and longer cold ischemia times, suggesting a role for increased utilization of these organs with careful recipient selection.
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Affiliation(s)
- Hope Werenski
- From the Department of Surgery, Section of Abdominal Organ Transplantation, Atrium Health Wake Forest Baptist, Winston-Salem, NC
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2
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Chang A, Schaubel DE, Chen M, Abt PL, Bittermann T. Trends and Outcomes of Hypothermic Machine Perfusion Preservation of Kidney Allografts in Simultaneous Liver and Kidney Transplantation in the United States. Transpl Int 2022; 35:10345. [PMID: 35356400 PMCID: PMC8958417 DOI: 10.3389/ti.2022.10345] [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: 01/07/2022] [Accepted: 01/18/2022] [Indexed: 11/18/2022]
Abstract
Optimal kidney graft outcomes after simultaneous liver-kidney (SLK) transplant may be threatened by the increased cold ischemia time and hemodynamic perturbations of dual organ transplantation. Hypothermic machine perfusion (MP) of kidney allografts may mitigate these effects. We analyzed U.S. trends and renal outcomes of hypothermic non-oxygenated MP vs. static cold storage (CS) of kidney grafts from 6,689 SLK transplants performed between 2005 and 2020 using the United Network for Organ Sharing database. Outcomes included delayed graft function (DGF), primary non-function (PNF), and kidney graft survival (GS). Overall, 17.2% of kidney allografts were placed on MP. Kidney cold ischemia time was longer in the MP group (median 12.8 vs. 10.0 h; p < 0.001). Nationally, MP utilization in SLK increased from <3% in 2005 to >25% by 2019. Center preference was the primary determinant of whether a graft underwent MP vs. CS (intraclass correlation coefficient 65.0%). MP reduced DGF (adjusted OR 0.74; p = 0.008), but not PNF (p = 0.637). Improved GS with MP was only observed with Kidney Donor Profile Index <20% (HR 0.71; p = 0.030). Kidney MP has increased significantly in SLK in the U.S. in a heterogeneous manner and with variable short-term benefits. Additional studies are needed to determine the ideal utilization for MP in SLK.
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Affiliation(s)
- Alex Chang
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Douglas E Schaubel
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Melissa Chen
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Peter L Abt
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Therese Bittermann
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
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3
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Dondossola D, Ravaioli M, Lonati C, Maroni L, Pini A, Accardo C, Germinario G, Antonelli B, Odaldi F, Zanella A, Siniscalchi A, Cescon M, Rossi G. The Role of Ex Situ Hypothermic Oxygenated Machine Perfusion and Cold Preservation Time in Extended Criteria Donation After Circulatory Death and Donation After Brain Death. Liver Transpl 2021; 27:1130-1143. [PMID: 33835695 DOI: 10.1002/lt.26067] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Revised: 03/08/2021] [Accepted: 03/29/2021] [Indexed: 02/06/2023]
Abstract
Hypothermic oxygenated machine perfusion (HOPE) has the potential to counterbalance the detrimental consequences of cold and warm ischemia time (WIT) in both donation after brain death (DBD) and donation after circulatory death (DCD). Herein we investigated the protective effects of HOPE in extended criteria donor (ECD) DBD and overextended WIT DCD grafts. The present retrospective case series included 50 livers subjected to end-ischemic HOPE or dual DHOPE in 2 liver transplantation (LT) centers from January 2018 to December 2019. All DCD donors were subjected to normothermic regional perfusion before organ procurement. Results are expressed as median (interquartile range [IQR]). In the study period, 21 grafts were derived from overextended WIT DCD donors (total WIT 54 [IQR, 40-60] minutes and 75% classified as futile), whereas 29 were from ECD DBD. A total of 3 biliary complications and 1 case of ischemia-type biliary lesion were diagnosed. The rate of early allograft dysfunction (EAD) was 20%, and those patients had higher Comprehensive Complication Index scores. Through a changing point analysis, cold preservation time >9 hours was associated with prolonged hospital stays (P = 0.02), higher rates of EAD (P = 0.009), and worst post-LT complications (P = 0.02). Logistic regression analyses indicated a significant relationship between cold preservation time and EAD. No differences were shown in terms of the early post-LT results between LTs performed with DCD and DBD. Overall, our data are fully comparable with benchmark criteria in LT. In conclusion, the application of DHOPE obtained satisfactory and promising results using ECD-DBD and overextended DCD grafts. Our findings indicate the need to reduce cold preservation time also in the setting of DHOPE, particularly for grafts showing poor quality.
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Affiliation(s)
- Daniele Dondossola
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.,Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Matteo Ravaioli
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Caterina Lonati
- Center for Preclinical Research, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Lorenzo Maroni
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Alessia Pini
- Department of Statistical Sciences, Università Cattolica del Sacro Cuore, Milan, Italy
| | - Caterina Accardo
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Giuliana Germinario
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Barbara Antonelli
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Federica Odaldi
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Alberto Zanella
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.,Department of Anesthesia and Critical Care, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Antonio Siniscalchi
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Cescon
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giorgio Rossi
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.,Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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4
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Moosburner S, Sauer IM, Förster F, Winklmann T, Gassner JMGV, Ritschl PV, Öllinger R, Pratschke J, Raschzok N. Early Allograft Dysfunction Increases Hospital Associated Costs After Liver Transplantation-A Propensity Score-Matched Analysis. Hepatol Commun 2021; 5:526-537. [PMID: 33681684 PMCID: PMC7917275 DOI: 10.1002/hep4.1651] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 10/07/2020] [Accepted: 11/05/2020] [Indexed: 12/16/2022] Open
Abstract
Concepts to ameliorate the continued mismatch between demand for liver allografts and supply include the acceptance of allografts that meet extended donor criteria (ECD). ECD grafts are generally associated with an increased rate of complications such as early allograft dysfunction (EAD). The costs of liver transplantation for the health care system with respect to specific risk factors remain unclear and are subject to change. We analyzed 317 liver transplant recipients from 2013 to 2018 for outcome after liver transplantation and hospital costs in a German transplant center. In our study period, 1-year survival after transplantation was 80.1% (95% confidence interval: 75.8%-84.6%) and median hospital stay was 33 days (interquartile rage: 24), with mean hospital costs of €115,924 (SD €113,347). There was a positive correlation between costs and laboratory Model for End-Stage Liver Disease score (rs = 0.48, P < 0.001), and the development of EAD increased hospital costs by €26,229. ECD grafts were not associated with a higher risk of EAD in our cohort. When adjusting for recipient-associated risk factors such as laboratory Model for End-Stage Liver Disease score, recipient age, and split liver transplantation with propensity score matching, only EAD and cold ischemia increased total costs. Conclusion: Our data show that EAD leads to significantly higher hospital costs for liver transplantation, which are primarily attributed to recipient health status. Strategies to reduce the incidence of EAD are needed to control costs in liver transplantation.
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Affiliation(s)
- Simon Moosburner
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Igor M Sauer
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Frank Förster
- Corporate ControllingCharité-Universitätsmedizin BerlinCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Thomas Winklmann
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Joseph Maria George Vernon Gassner
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Paul V Ritschl
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Robert Öllinger
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Johann Pratschke
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Nathanael Raschzok
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
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Montenovo MI, Perkins JD, Kling CE, Sibulesky L, Dick AA, Reyes JD. Machine Perfusion Decreases Delayed Graft Function in Donor Grafts With High Kidney Donor Profile Index. EXP CLIN TRANSPLANT 2021; 19:8-13. [DOI: 10.6002/ect.2019.0139] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Foucher Y, Fournier MC, Legendre C, Morelon E, Buron F, Girerd S, Ladrière M, Mourad G, Garrigue V, Glotz D, Lefaucheur C, Cassuto E, Albano L, Giral M, Dantal J. Comparison of machine perfusion versus cold storage in kidney transplant recipients from expanded criteria donors: a cohort-based study. Nephrol Dial Transplant 2020; 35:1043-1070. [PMID: 32516809 DOI: 10.1093/ndt/gfz175] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 07/26/2019] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Most studies comparing the efficacy of hypothermic machine perfusion (HMP) versus static cold storage (SCS) are based on short-term outcomes. We aimed to better evaluate the mid-term impact of HMP in patients receiving expanded criteria donor (ECD) kidneys. METHODS The analyses were based on the French Données Informatisées et VAlidées en Transplantation (DIVAT) observational cohort. Patients aged ≥45 years transplanted for the first or second times from an ECD donor since 2010 were studied. Our study reported the graft and/or patient survivals and the incidence of acute rejection episode. The Cox models and the Kaplan-Meier estimators, weighted on the propensity score, were used to study the times-to-events. RESULTS Among the 2019 included patients, 1073 were in the SCS group versus 946 in the HMP group. The mean life expectancy with functioning graft was 5.7 years [95% confidence interval (CI) 5.4-6.1] for the HMP cohort followed-up for 8 years post-transplantation versus 6.0 years (95% CI 5.7-6.2) for the SCS group. These mid-term results were comparable in the patients receiving grafts from donors aged ≥70 years and in the transplantations with cold ischaemia time ≥18 h. CONCLUSIONS Our study challenges the utility of using HMP to improve mid-term patient and graft survival. Nevertheless, the improvement of the short-term outcomes is indisputable. It is necessary to continue technological innovations to obtain long-term results.
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Affiliation(s)
- Yohann Foucher
- INSERM UMR 1246 - SPHERE, Nantes University, Tours University, Nantes, France.,Centre Hospitalier Universitaire de Nantes, Nantes, France
| | | | - Christophe Legendre
- Kidney Transplant Center, Necker University Hospital, APHP, RTRS « Centaure », Paris Descartes and Sorbonne Paris Cité Universities, Paris, France
| | - Emmanuel Morelon
- Nephrology, Transplantation and Clinical Immunology Department, RTRS « Centaure », Edouard Herriot University Hospital, Hospices Civils, Lyon, France
| | - Fanny Buron
- Nephrology, Transplantation and Clinical Immunology Department, RTRS « Centaure », Edouard Herriot University Hospital, Hospices Civils, Lyon, France
| | - Sophie Girerd
- Renal Transplantation Department, Brabois University Hospital, Nancy, France
| | - Marc Ladrière
- Renal Transplantation Department, Brabois University Hospital, Nancy, France
| | - Georges Mourad
- Nephrology, Dialysis and Transplantation Department, Lapeyronie University Hospital, Montpellier, France
| | - Valérie Garrigue
- Nephrology, Dialysis and Transplantation Department, Lapeyronie University Hospital, Montpellier, France
| | - Denis Glotz
- Paris Translational Research Center for Organ Transplantation & Department of Nephrology and Transplantation, Hopital Saint Louis, Université Paris VII and INSERM U 1160, Paris, France
| | - Carmen Lefaucheur
- Paris Translational Research Center for Organ Transplantation & Department of Nephrology and Transplantation, Hopital Saint Louis, Université Paris VII and INSERM U 1160, Paris, France
| | - Elisabeth Cassuto
- Department of Nephrology and Renal Transplantation, Hospital Pasteur, Nice, France
| | - Laetitia Albano
- Department of Nephrology and Renal Transplantation, Hospital Pasteur, Nice, France
| | - Magali Giral
- Centre Hospitalier Universitaire de Nantes, Nantes, France.,Centre d'Investigation Clinique en Biothérapie, Labex Transplantex, Nantes, France.,Centre de Recherche en Transplantation et Immunologie INSERM UMR1064, Université de Nantes, Centre Hospitalier Universitaire de Nantes, RTRS « Centaure », Nantes, France
| | - Jacques Dantal
- Centre Hospitalier Universitaire de Nantes, Nantes, France.,Centre de Recherche en Transplantation et Immunologie INSERM UMR1064, Université de Nantes, Centre Hospitalier Universitaire de Nantes, RTRS « Centaure », Nantes, France
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7
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Iglesias-González E, Torras-Ambros J. Impacto de la perfusión hipotérmica pulsativa en el injerto renal de donante subóptimo: nuestra experiencia inicial. ENFERMERÍA NEFROLÓGICA 2020. [DOI: 10.37551/s2254-28842020007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
Objetivo: Estudios recientes han demostrado que el mantenimiento de la viabilidad de riñones con criterios expandidos durante su preservación sea un reto. La máquina de perfusión hipotérmica pretende mitigar el efecto del almacenamiento en frío sobre la calidad del órgano cuando el tiempo de isquemia fría es prolongada o el donante subóptimo.Objetivo: Evaluar las complicaciones que presentan los pacientes trasplantados renales con preservación está-tica fría o perfusión hipotérmica pulsátil.Material y Método: Estudio observacional retrospec-tivo durante 2010-2012 donde se incluyeron todos los trasplantes renales realizados en un hospital de tercer nivel. Las variables de estudio: estancia hospitalaria, horas de isquemia, necesidad de diálisis y número de sesiones post trasplante y el dispositivo de almacena-miento, edad y patologías asociadas al donante.Resultados: Se realizaron 175 trasplantes donde 70 procedieron de donantes ≥65 años. Se perfundieron en máquina 30 riñones y en 40 se utilizó la preservación estática. Nuestros hallazgos respecto al uso de la má-quina de perfusión conllevan un descenso en la estancia media hospitalaria y una menor necesidad de hemodiá-lisis postrasplante.Conclusiones: Debido al alto porcentaje de órganos procedentes de donantes de edad avanzada y difíciles de preservar, resulta fundamental buscar técnicas de perfusión intravascular continua para una preservación más efectiva del órgano.
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Affiliation(s)
- Estefanía Iglesias-González
- Departamento Extracción Multiorgánica y Trasplante Renal. Hospital Universitario de Bellvitge. Hospitalet de Llobregat. Barcelona. España
| | - Joan Torras-Ambros
- Departamento de Nefrología. Hospital Universitario de Bellvitge. Hospitalet de Llobregat. Barcelona. España
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Rijkse E, IJzermans JNM, Minnee RC. Machine perfusion in abdominal organ transplantation: Current use in the Netherlands. World J Transplant 2020; 10:15-28. [PMID: 32110511 PMCID: PMC7031624 DOI: 10.5500/wjt.v10.i1.15] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 12/03/2019] [Accepted: 12/19/2019] [Indexed: 02/05/2023] Open
Abstract
Scarcity of donor organs and the increment in patients awaiting a transplant increased the use of organs from expanded criteria donors or donation after circulatory death. Due to the suboptimal outcomes of these donor organs, there is an increased interest in better preservation methods, such as ex vivo machine perfusion or abdominal regional perfusion to improve outcomes. This state-of-the-art review aims to discuss the available types of perfusion techniques, its potential benefits and the available evidence in kidney, liver and pancreas transplantation. Additionally, translational steps from animal models towards clinical studies will be described, as well as its application to clinical practice, with the focus on the Netherlands. Despite the lack of evidence from randomized controlled trials, currently available data suggest especially beneficial effects of normothermic regional perfusion on biliary complications and ischemic cholangiopathy after liver transplantation. For ex vivo machine perfusion in kidney transplantation, hypothermic machine perfusion has proven to be beneficial over static cold storage in a randomized controlled trial, while normothermic machine perfusion is currently under investigation. For ex vivo machine perfusion in liver transplantation, normothermic machine perfusion has proven to reduce discard rates and early allograft dysfunction. In response to clinical studies, hypothermic machine perfusion for deceased donor kidneys has already been implemented as standard of care in the Netherlands.
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Affiliation(s)
- Elsaline Rijkse
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC University Medical Center, Rotterdam 3015 GD, Netherlands
| | - Jan NM IJzermans
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC University Medical Center, Rotterdam 3015 GD, Netherlands
| | - Robert C Minnee
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC University Medical Center, Rotterdam 3015 GD, Netherlands
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9
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Gelpi R, Paredes D, Rodríguez-Villar C, Roque R, Ruiz A, Adalia R, Peri-Cusí L, Sole M, Oppenheimer F, Diekmann F. The development of a predictive model of graft function in uncontrolled donors after circulatory death: validity of a pulsatile renal preservation machine cut-off value for kidney acceptance. Nephrol Dial Transplant 2019; 34:531-538. [PMID: 30085267 DOI: 10.1093/ndt/gfy241] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 06/14/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The criteria for kidney suitability in uncontrolled donors after circulatory death (uDCD) procured after regional normothermic perfusion are based on macroscopic appearance and renal haemodynamic values with final renal resistance (FRR). However, these criteria have not been analysed to predict the future graft function. This study presents a model to predict the outcome in uDCD kidneys and define the predictive FRR value. METHODS All uDCD kidney transplants performed in our hospital from 2004 to 2016 were included. Donors and recipients and pre-transplantation data are described. The endpoint was glomerular filtration rate (GFR) ≥30 mL/min at 6 months after transplantation. RESULTS A total of 194 recipients were included. FRR in donors ≥60 years old was (mean ± SD) 0.27 ± 0.11 versus 0.22 ± 0.09 mmHg/mL/min in donors <60 years (P = 0.042). Kidney survival was 88.2% versus 84% at 12 months and 60.7% versus 30.8% at 120 months (P = 0.067). For the group of recipients from donors ≥60 years, the FRR was 0.37 ± 0.08 mmHg/mL/min in the GFR <30 mL/min group versus 0.18 ± 0.06 mmHg/mL/min in the GFR ≥30 mL/min group (P < 0.001). The value FRR ≥0.3 mmHg/mL/min predicts 59-79% of GFR <30 mL/min [odds ratio = 2.16, 95% confidence interval (CI) 1.80-6.40; P < 0.001]. The predictive accuracy of FRR for GFR by ROC curve was 0.968 (95% CI). The best cut-off for FRR was 0.3 mmHg/mL/min to predict GFR at 6 months with a sensitivity of 67%, specificity of 100%, positive predictive value of 83% and negative predictive value of 92%. CONCLUSIONS Our results suggest that in uDCD donors the combination of donor age ≥60 years together with FRR ≥0.3 mmHg/mL/min could predict poor outcome at 6 months after transplantation in low immunological risk recipients.
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Affiliation(s)
- Rosana Gelpi
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - David Paredes
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Camino Rodríguez-Villar
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Rebeca Roque
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Angel Ruiz
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Ramon Adalia
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Luis Peri-Cusí
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Manel Sole
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Federico Oppenheimer
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Fritz Diekmann
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
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10
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Samoylova ML, Nash A, Kuchibhatla M, Barbas AS, Brennan TV. Machine perfusion of donor kidneys may reduce graft rejection. Clin Transplant 2019; 33:e13716. [DOI: 10.1111/ctr.13716] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Revised: 09/08/2019] [Accepted: 09/10/2019] [Indexed: 11/30/2022]
Affiliation(s)
| | - Amanda Nash
- Department of Surgery Duke University Medical Center Durham North Carolina
| | | | - Andrew S. Barbas
- Department of Surgery Duke University Medical Center Durham North Carolina
| | - Todd V. Brennan
- Department of Surgery Cedars‐Sinai Medical Center Los Angeles California
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11
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Aburawi MM, Fontan FM, Karimian N, Eymard C, Cronin S, Pendexter C, Nagpal S, Banik P, Ozer S, Mahboub P, Delmonico FL, Yeh H, Uygun K, Markmann JF. Synthetic hemoglobin-based oxygen carriers are an acceptable alternative for packed red blood cells in normothermic kidney perfusion. Am J Transplant 2019; 19:2814-2824. [PMID: 30938927 PMCID: PMC6763345 DOI: 10.1111/ajt.15375] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 02/26/2019] [Accepted: 03/20/2019] [Indexed: 01/25/2023]
Abstract
Normothermic machine perfusion presents a novel platform for pretransplant assessment and reconditioning of kidney grafts. Maintaining the metabolic activity of a preserved graft at physiologic levels requires an adequate oxygen supply, typically delivered by crystalloid solutions supplemented with red blood cells. In this study, we explored the feasibility of using a synthetic hemoglobin-based oxygen carrier (HBOC) in human kidney normothermic perfusion. Fourteen discarded human kidneys were perfused for 6 hours at a mean temperature of 37°C using a pressure-controlled system. Kidneys were perfused with a perfusion solution supplemented with either HBOC (n = 7) or packed red blood cells (PRBC) (n = 7) to increase oxygen-carrying capacity. Renal artery resistance, oxygen extraction, metabolic activity, energy stores, and histological features were evaluated. Throughout perfusion, kidneys from both groups exhibited comparable behavior regarding vascular flow (P = .66), oxygen consumption (P = .88), and reconstitution of tissue adenosine triphosphate (P = .057). Lactic acid levels were significantly higher in kidneys perfused with PRBC (P = .007). Histological findings were comparable between groups, and there was no evidence of histological damage caused by the HBOC. This feasibility experiment demonstrates that a HBOC solution can offer a logistically more convenient off-the-shelf alternative to PRBC in normothermic machine perfusion of human kidneys.
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Affiliation(s)
- Mohamed M Aburawi
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Fermin M Fontan
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Negin Karimian
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts,Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Corey Eymard
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Stephanie Cronin
- Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Casie Pendexter
- Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Sonal Nagpal
- Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Peony Banik
- Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Sinan Ozer
- Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Paria Mahboub
- Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Francis L Delmonico
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts,New England Donor Services, Waltham, Massachusetts
| | - Heidi Yeh
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Korkut Uygun
- Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - James F Markmann
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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12
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Leite RRDA, Schanaider A, da-Fonseca ER, Xavier VL, de-Miranda LCD. Machine perfusion versus cold storage in renal preservation of deceased donors with brain death: systematic review and meta-analysis. ACTA ACUST UNITED AC 2019; 46:e2079. [PMID: 31090864 DOI: 10.1590/0100-6991e-20192079] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 02/05/2019] [Indexed: 11/21/2022]
Abstract
With the increasing use of machine perfusion in kidney transplantation, it has been observed that dynamic ischemia correlates with the improvement of organ preservation. In this context, we performed a systematic review that aimed to evaluate the efficacy of the portable machine perfusion (LifePort Kidney Transporter Machine®), used in Brazil, compared to cold storage, regarding the delayed graft function of deceased donors with brain death. Literature search was carried out in LILACS, MEDLINE via PubMed, Scopus, Clarivate Analytics, Cochrane Library, Embase, and SciELO, as well as in Google Scholar manually. The systematic review consisted only of randomized clinical trials. For meta-analysis, relative risk and odds ratio were evaluated. Eighty-six documents were identified and two papers from European and Brazilian groups were selected at the end, with eligibility criteria for meta-analysis. In these, 374 kidneys were assigned to machine perfusion and 374 kidneys were assigned to cold storage. Delayed graft function was observed in 84 and 110 patients, respectively. In meta-analysis, a risk ratio of 0.7568 (p=0.0151) and an odds ratio of 0.6665 (p=0.0225) were obtained, both with a 95% confidence interval. Machine perfusion reduced the incidence of delayed graft function of deceased donors with brain death.
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Affiliation(s)
- Ricardo Ribas de Almeida Leite
- Universidade Federal do Rio de Janeiro, Programa de Pós-Graduação em Ciências Cirúrgicas, Departamento de Cirurgia, Rio de Janeiro, RJ, Brasil
| | - Alberto Schanaider
- Universidade Federal do Rio de Janeiro, Departamento de Cirurgia, Rio de Janeiro, RJ, Brasil
| | | | - Vinicius Layter Xavier
- Universidade do Estado do Rio de Janeiro, Instituto de Matemática e Estatística, Departamento de Estatística, Rio de Janeiro, RJ, Brasil
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13
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The Benefits of Hypothermic Machine Preservation and Short Cold Ischemia Times in Deceased Donor Kidneys. Transplantation 2019; 102:1344-1350. [PMID: 29570164 DOI: 10.1097/tp.0000000000002188] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Hypothermic machine perfusion (HMP) of deceased donor kidneys is associated with better outcome when compared to static cold storage (CS). Nevertheless, there is little evidence whether kidneys with short cold ischemia time (CIT) also benefit from HMP and whether HMP can safely extend CIT. METHODS We analyzed prospectively collected data from the Machine Preservation Trial, an international randomized controlled trial. Seven hundred fifty-two consecutive renal transplants were included: 1 kidney of each of the 376 donors was preserved by HMP, the contralateral organ was preserved by CS. RESULTS The mean CIT was 3:05 PM (SD, 4:58 AM). A subgroup analysis was performed, groups were based on CIT duration: 0 to 10 hours, 10 to 15 hours, 15 to 20 hours, or 20 hours or longer. Delayed graft function (DGF) incidence in the subgroup with up to 10 hours CIT was 6.0% (N = 3/50) in the HMP arm and 28.1% (N = 18/64) in the CS arm (univariable P = 0.002; multivariable odds ratio [OR], 0.02; P = 0.007). Cold ischemia time remained an independent risk factor for DGF for machine perfused kidneys recovered from donation after brain death donors (OR, 1.06; 95% confidence interval [CI], 1.017-1.117; P = 0.008), donation after circulatory death donors (OR, 1.13; 95% CI, 1.035-1.233; P = 0.006) and expanded criteria donors (OR, 1.14; 95% CI, 1.057-1.236; P = 0.001). CONCLUSIONS In conclusion, HMP resulted in remarkably lower rates of DGF in renal grafts that were transplanted after a short CIT. Also, CIT remained an independent risk factor for DGF in HMP-preserved kidneys.
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14
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Ravaioli M, De Pace V, Comai G, Capelli I, Baraldi O, D'Errico A, Bertuzzo VR, Del Gaudio M, Zanfi C, D'Arcangelo GL, Cuna V, Siniscalchi A, Sangiorgi G, La Manna G. Preliminary experience of sequential use of normothermic and hypothermic oxygenated perfusion for donation after circulatory death kidney with warm ischemia time over the conventional criteria - a retrospective and observational study. Transpl Int 2018; 31:1233-1244. [DOI: 10.1111/tri.13311] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Affiliation(s)
- Matteo Ravaioli
- Unit of General and Transplant Surgery; Department of Medical and Surgical Sciences; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
| | - Vanessa De Pace
- Unit of General and Transplant Surgery; Department of Medical and Surgical Sciences; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
| | - Giorgia Comai
- Unit of Nephrology; Dialysis and Transplantation; Department of Experimental Diagnostic and Specialty Medicine; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
| | - Irene Capelli
- Unit of Nephrology; Dialysis and Transplantation; Department of Experimental Diagnostic and Specialty Medicine; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
| | - Olga Baraldi
- Unit of Nephrology; Dialysis and Transplantation; Department of Experimental Diagnostic and Specialty Medicine; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
| | - Antonietta D'Errico
- Unit of Oncology and Transplant Pathology; Department of Experimental Diagnostic and Specialty Medicine; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
| | - Valentina Rosa Bertuzzo
- Unit of General and Transplant Surgery; Department of Medical and Surgical Sciences; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
| | - Massimo Del Gaudio
- Unit of General and Transplant Surgery; Department of Medical and Surgical Sciences; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
| | - Chiara Zanfi
- Unit of General and Transplant Surgery; Department of Medical and Surgical Sciences; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
| | - Giovanni Liviano D'Arcangelo
- Unit of Nephrology; Dialysis and Transplantation; Department of Experimental Diagnostic and Specialty Medicine; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
| | - Vania Cuna
- Unit of Nephrology; Dialysis and Transplantation; Department of Experimental Diagnostic and Specialty Medicine; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
| | - Antonio Siniscalchi
- Unit of Anesthesiology; Department of Medical and Surgical Sciences; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
| | - Gabriela Sangiorgi
- Emilia Romagna Transplant Reference Center; Department of Medical and Surgical Sciences; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
| | - Gaetano La Manna
- Unit of Nephrology; Dialysis and Transplantation; Department of Experimental Diagnostic and Specialty Medicine; University of Bologna Sant'Orsola Malpighi Hospital; Bologna Italy
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15
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Sandal S, Luo X, Massie AB, Paraskevas S, Cantarovich M, Segev DL. Machine perfusion and long-term kidney transplant recipient outcomes across allograft risk strata. Nephrol Dial Transplant 2018; 33:1251-1259. [PMID: 29474675 PMCID: PMC6030984 DOI: 10.1093/ndt/gfy010] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Accepted: 12/27/2017] [Indexed: 12/22/2022] Open
Abstract
Background The use of machine perfusion (MP) in kidney transplantation lowers delayed graft function (DGF) and improves 1-year graft survival in some, but not all, grafts. These associations have not been explored in grafts stratified by the Kidney Donor Profile index (KDPI). Methods We analyzed 78 207 deceased-donor recipients using the Scientific Registry of Transplant Recipients data from 2006 to 2013. The cohort was stratified using the standard criteria donor/expanded criteria donor (ECD)/donation after cardiac death (DCD)/donation after brain death (DBD) classification and the KDPI scores. In each subgroup, MP use was compared with cold storage. Results The overall DGF rate was 25.4% and MP use was associated with significantly lower DGF in all but the ECD-DCD donor subgroup. Using the donor source classification, the use of MP did not decrease death-censored graft failure (DCGF), except in the ECD-DCD subgroup from 0 to 1 year {adjusted hazard ratio [aHR] 0.56 [95% confidence interval (CI) 0.32-0.98]}. In the ECD-DBD subgroup, higher DCGF from 1 to 5 years was noted [aHR 1.15 (95% CI 1.01-1.31)]. Also, MP did not lower all-cause graft failure except in the ECD-DCD subgroup from 0 to 1 year [aHR = 0.59 (95% CI 0.38-0.91)]. Using the KDPI classification, MP did not lower DCGF or all-cause graft failure, but in the ≤70 subgroup, higher DCGF [aHR 1.16 (95% CI 1.05-1.27)] and higher all-cause graft failure [aHR 1.10 (95% CI 1.02-1.18)] was noted. Lastly, MP was not associated with mortality in any subgroup. Conclusions Overall, MP did not lower DCGF. Neither classification better risk-stratified kidneys that have superior graft survival with MP. We question their widespread use in all allografts as an ideal approach to organ preservation.
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Affiliation(s)
- Shaifali Sandal
- Department of Medicine, Divisions of Nephrology and Multi-Organ Transplant Program, McGill University Health Centre, Montreal, QC, Canada
| | - Xun Luo
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Allan B Massie
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Steven Paraskevas
- Department of Surgery, Division of Multi-Organ Transplant Program, McGill University Health Centre, Montreal, QC, Canada
| | - Marcelo Cantarovich
- Department of Medicine, Divisions of Nephrology and Multi-Organ Transplant Program, McGill University Health Centre, Montreal, QC, Canada
| | - Dorry L Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
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16
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Doorschodt BM, Schreinemachers MCJ, Florquin S, Lai W, Sitzia M, Zernecke A, Tolba RH. Evaluation of a Novel System for Hypothermic Oxygenated Pulsatile Perfusion Preservation. Int J Artif Organs 2018; 32:728-38. [DOI: 10.1177/039139880903201004] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Background Recently, a novel innovative machine perfusion (MP) system for hypothermic oxygenated pulsatile perfusion called the Airdrive (AD) has been developed. The aim of the study was to evaluate the biological safety of the AD system for perfusion preservation of kidney grafts in a porcine autotransplantation model using the low-viscosity perfusion solution Polysol (PS) in comparison with cold storage (CS) using PS or the University of Wisconsin solution (UW). In addition, we evaluated real-time microcirculation parameters. At sacrifice, grafts were retrieved for histological analysis and immunohistochemistry Methods After assessment of the microcirculation, left kidneys were retrieved. Following the washout, kidneys were preserved for 20 hr using AD-PS, CS-PS or CS-UW. Thereafter, contralateral kidneys were removed followed by heterotopic autotransplantation of the preserved graft. Seven days after transplantation animals were sacrificed with retrieval of the grafts for histological analysis. Renal function, renal microcirculation and tissue injury including the proliferative response of tubular epithelial cells (TECs) were compared. Results Preservation using AD-PS or CS-PS resulted in higher microcirculatory flow compared with CS-UW. Improved recovery of renal function was seen in the AD-PS and CS-PS groups compared with CS-UW. Structural integrity was better preserved using AD-PS compared with both CS groups. Proliferative response of TECs was higher in CS-UW preserved grafts compared to grafts preserved using AD-PS. Conclusion This study demonstrates the biological safety of the AD system in a porcine autotransplantation model. Also, the microcirculation was better preserved and less morphological injury was observed after 20 hr MP compared with CS.
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Affiliation(s)
- Benedict M. Doorschodt
- Institute for Laboratory Animal Science & Experimental Surgery, RWTH-Aachen University, Aachen - Germany
| | | | - Sandrine Florquin
- Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam - The Netherlands
| | - Wei Lai
- House of Experimental Therapy, University of Bonn, Bonn - Germany
| | - Mario Sitzia
- House of Experimental Therapy, University of Bonn, Bonn - Germany
| | - Alma Zernecke
- Institute for Molecular Cardiovascular Research, Institute of Pathology, RWTH-Aachen University, Aachen - Germany
| | - Rene H. Tolba
- Institute for Laboratory Animal Science & Experimental Surgery, RWTH-Aachen University, Aachen - Germany
- House of Experimental Therapy, University of Bonn, Bonn - Germany
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17
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Functional Results of Renal Preservation in Hypothermic Pulsatile Machine Perfusion Versus Cold Preservation: Systematic Review and Meta-Analysis of Clinical Trials. Transplant Proc 2018; 50:24-32. [DOI: 10.1016/j.transproceed.2017.12.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Revised: 11/02/2017] [Accepted: 12/04/2017] [Indexed: 01/13/2023]
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18
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Krezdorn N, Tasigiorgos S, Wo L, Turk M, Lopdrup R, Kiwanuka H, Win TS, Bueno E, Pomahac B. Tissue conservation for transplantation. Innov Surg Sci 2017; 2:171-187. [PMID: 31579751 PMCID: PMC6754021 DOI: 10.1515/iss-2017-0010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Accepted: 06/27/2017] [Indexed: 02/07/2023] Open
Abstract
Pathophysiological changes that occur during ischemia and subsequent reperfusion cause damage to tissues procured for transplantation and also affect long-term allograft function and survival. The proper preservation of organs before transplantation is a must to limit these injuries as much as possible. For decades, static cold storage has been the gold standard for organ preservation, with mechanical perfusion developing as a promising alternative only recently. The current literature points to the need of developing dedicated preservation protocols for every organ, which in combination with other interventions such as ischemic preconditioning and therapeutic additives offer the possibility of improving organ preservation and extending it to multiple times its current duration. This review strives to present an overview of the current body of knowledge with regard to the preservation of organs and tissues destined for transplantation.
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Affiliation(s)
- Nicco Krezdorn
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Burn Center, Hannover Medical School, Hannover, Germany
| | - Sotirios Tasigiorgos
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Luccie Wo
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Marvee Turk
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Rachel Lopdrup
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Harriet Kiwanuka
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Thet-Su Win
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Ericka Bueno
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Bohdan Pomahac
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
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19
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20
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Association Between Delayed Graft Function and Graft Loss in Donation After Cardiac Death Kidney Transplants-A Paired Kidney Registry Analysis. Transplantation 2017; 101:1139-1143. [PMID: 28538652 DOI: 10.1097/tp.0000000000001323] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Delayed graft function (DGF) is an established complication after donation after cardiac death (DCD) kidney transplants, but the impact of DGF on graft outcomes is uncertain. To minimize donor variability and bias, a paired donor kidney analysis was undertaken where 1 kidney developed DGF and the other did not develop DGF using data from the Australia and New Zealand Dialysis and Transplant Registry. METHODS Using paired DCD kidney data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between DGF, graft and patient outcomes between 1994 and 2012 using adjusted Cox regression models. RESULTS Of the 74 pairs of DCD kidneys followed for a median of 1.9 years (408 person-years), a greater proportion of recipients with DGF had experienced overall graft loss and death-censored graft loss at 3 years compared with those without DGF (14% vs 4%, P = 0.04 and 11% vs 0%, P < 0.01, respectively). Compared with recipients without DGF, the adjusted hazard ratio for overall graft loss at 3 years for recipients with DGF was 4.31 (95% confidence interval [95% CI], 1.13-16.44). The adjusted hazard ratio for acute rejection and all-cause mortality at 3 years in recipients who have experienced DGF were 0.98 (95% CI, 0.96-1.01) and 1.70 (95% CI, 0.36-7.93), respectively, compared with recipients without DGF. CONCLUSIONS Recipients of DCD kidneys with DGF experienced a higher incidence of overall and death-censored graft loss compared with those without DGF. Strategies aim to reduce the risk of DGF could potentially improve graft survival in DCD kidney transplants.
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21
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Continuous Normothermic Ex Vivo Kidney Perfusion Improves Graft Function in Donation After Circulatory Death Pig Kidney Transplantation. Transplantation 2017; 101:754-763. [PMID: 27467537 DOI: 10.1097/tp.0000000000001343] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Donation after circulatory death (DCD) is current clinical practice to increase the donor pool. Deleterious effects on renal graft function are described for hypothermic preservation. Therefore, current research focuses on investigating alternative preservation techniques, such as normothermic perfusion. METHODS We compared continuous pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) with static cold storage (SCS) in a porcine model of DCD autotransplantation. After 30 minutes of warm ischemia, right kidneys were removed from 30-kg Yorkshire pigs and preserved with 8-hour NEVKP or in 4°C histidine-tryptophan-ketoglutarate solution (SCS), followed by kidney autotransplantation. RESULTS Throughout NEVKP, electrolytes and pH values were maintained. Intrarenal resistance decreased over the course of perfusion (0 hour, 1.6 ± 0.51 mm per minute vs 7 hours, 0.34 ± 0.05 mm Hg/mL per minute, P = 0.005). Perfusate lactate concentration also decreased (0 hour, 10.5 ± 0.8 vs 7 hours, 1.4 ± 0.3 mmol/L, P < 0.001). Cellular injury markers lactate dehydrogenase and aspartate aminotransferase were persistently low (lactate dehydrogenase < 100 U/L, below analyzer range; aspartate aminotransferase 0 hour, 15.6 ± 9.3 U/L vs 7 hours, 24.8 ± 14.6 U/L, P = 0.298). After autotransplantation, renal grafts preserved with NEVKP demonstrated lower serum creatinine on days 1 to 7 (P < 0.05) and lower peak values (NEVKP, 5.5 ± 1.7 mg/dL vs SCS, 11.1 ± 2.1 mg/dL, P = 0.002). The creatinine clearance on day 4 was increased in NEVKP-preserved kidneys (NEVKP, 39 ± 6.4 vs SCS, 18 ± 10.6 mL/min; P = 0.012). Serum neutrophil gelatinase-associated lipocalin at day 3 was lower in the NEVKP group (1267 ± 372 vs 2697 ± 1145 ng/mL, P = 0.029). CONCLUSIONS Continuous pressure-controlled NEVKP improves renal function in DCD kidney transplantation. Normothermic ex vivo kidney perfusion might help to decrease posttransplant delayed graft function rates and to increase the donor pool.
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22
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Ex vivo machine perfusion for renal graft preservation. Transplant Rev (Orlando) 2017; 32:1-9. [PMID: 28483273 DOI: 10.1016/j.trre.2017.04.002] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2016] [Revised: 04/04/2017] [Accepted: 04/17/2017] [Indexed: 12/22/2022]
Abstract
Kidney transplantation is the treatment of choice for end-stage renal disease. Despite its superiority over dialysis, the persisting organ shortage remains a major drawback. Additional sources to increase the donor pool are grafts recovered from extended criteria donors (ECD) and donation after circulatory death (DCD). Although transplantation of marginal grafts demonstrates promising outcomes, increased rates of primary non-function, delayed graft function, and reduced graft survival have been reported. Cold ischemic injury, caused by static cold storage is a significant risk factor for poor outcome. Machine perfusion (MP) at various temperatures bears the potential to improve organ preservation, assessment, and repair. While hypothermic machine perfusion (HMP) is well established in clinical practice, modified HMP, subnormothermic machine perfusion (SMP), and normothermic machine perfusion (NMP) are novel emerging strategies with the potential to significantly improve the outcome of marginal kidney grafts. This review summarizes findings and recent advances from pre-clinical and clinical machine perfusion studies, organized by temperature, and discusses potential future developments for graft assessment and repair.
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23
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Kaths JM, Cen JY, Chun YM, Echeverri J, Linares I, Ganesh S, Yip P, John R, Bagli D, Mucsi I, Ghanekar A, Grant DR, Robinson LA, Selzner M. Continuous Normothermic Ex Vivo Kidney Perfusion Is Superior to Brief Normothermic Perfusion Following Static Cold Storage in Donation After Circulatory Death Pig Kidney Transplantation. Am J Transplant 2017; 17:957-969. [PMID: 27647696 DOI: 10.1111/ajt.14059] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Accepted: 09/07/2016] [Indexed: 01/25/2023]
Abstract
Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) versus short periods of normothermic ex vivo kidney perfusion (NEVKP) after SCS versus prolonged, continuous NEVKP with near avoidance of SCS on kidney function after transplantation. Following 30 min of warm ischemia, kidneys were removed from 30-kg Yorkshire pigs and preserved for 16 h with (A) 16 h SCS, (B) 15 h SCS + 1 h NEVKP, (C) 8 h SCS + 8 h NEVKP, and (D) 16 h NEVKP. After contralateral kidney resection, grafts were autotransplanted and pigs followed up for 8 days. Perfusate injury markers such as aspartate aminotransferase and lactate dehydrogenase remained low; lactate decreased significantly until end of perfusion in groups C and D (p < 0.001 and p = 0.002). Grafts in group D demonstrated significantly lower serum creatinine peak when compared to all other groups (p < 0.001) and 24-h creatinine clearance at day 3 after surgery was significantly higher (63.4 ± 19.0 mL/min) versus all other groups (p < 0.001). Histological assessment on day 8 demonstrated fewer apoptotic cells in group D (p = 0.008). In conclusion, prolonged, continuous NEVKP provides superior short-term outcomes following DCD kidney transplantation versus SCS or short additional NEVKP following SCS.
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Affiliation(s)
- J M Kaths
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.,Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.,Department of General, Visceral, and Transplant Surgery, University Medical Center Mainz, Mainz, Germany
| | - J Y Cen
- Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Y M Chun
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - J Echeverri
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - I Linares
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - S Ganesh
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - P Yip
- Laboratory Medicine & Pathobiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - R John
- Laboratory Medicine & Pathobiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - D Bagli
- Departments of Surgery (Urology) & Physiology, The Hospital for Sick Children, Toronto, Ontario, Canada.,Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - I Mucsi
- Multi Organ Transplant Program, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - A Ghanekar
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - D R Grant
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - L A Robinson
- Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.,Program in Cell Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
| | - M Selzner
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
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Liu S, Pang Q, Zhang J, Zhai M, Liu S, Liu C. Machine perfusion versus cold storage of livers: a meta-analysis. Front Med 2016; 10:451-464. [PMID: 27837413 DOI: 10.1007/s11684-016-0474-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2015] [Accepted: 07/19/2016] [Indexed: 12/18/2022]
Abstract
Different organ preservation methods are key factors influencing the results of liver transplantation. In this study, the outcomes of experimental models receiving donation after cardiac death (DCD) livers preserved through machine perfusion (MP) or static cold storage (CS) were compared by conducting a meta-analysis. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated to compare pooled data from two animal species. Twenty-four studies involving MP preservation were included in the meta-analysis. Compared with CS preservation, MP can reduce the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and hyaluronic acid (HA) and the changes in liver weight. By contrast, MP can enhance bile production and portal vein flow (PVF). Alkaline phosphatase (ALP) levels and histological changes significantly differed between the two preservation methods. In conclusion, MP of DCD livers is superior to CS in experimental animals.
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Affiliation(s)
- Sushun Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Qing Pang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Jingyao Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Mimi Zhai
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Sinan Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Chang Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China.
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25
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Hameed AM, Pleass HC, Wong G, Hawthorne WJ. Maximizing kidneys for transplantation using machine perfusion: from the past to the future: A comprehensive systematic review and meta-analysis. Medicine (Baltimore) 2016; 95:e5083. [PMID: 27749583 PMCID: PMC5059086 DOI: 10.1097/md.0000000000005083] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 09/11/2016] [Accepted: 09/15/2016] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The two main options for renal allograft preservation are static cold storage (CS) and machine perfusion (MP). There has been considerably increased interest in MP preservation of kidneys, however conflicting evidence regarding its efficacy and associated costs have impacted its scale of clinical uptake. Additionally, there is no clear consensus regarding oxygenation, and hypo- or normothermia, in conjunction with MP, and its mechanisms of action are also debated. The primary aims of this article were to elucidate the benefits of MP preservation with and without oxygenation, and/or under normothermic conditions, when compared with CS prior to deceased donor kidney transplantation. METHODS Clinical (observational studies and prospective trials) and animal (experimental) articles exploring the use of renal MP were assessed (EMBASE, Medline, and Cochrane databases). Meta-analyses were conducted for the comparisons between hypothermic MP (hypothermic machine perfusion [HMP]) and CS (human studies) and normothermic MP (warm (normothermic) perfusion [WP]) compared with CS or HMP (animal studies). The primary outcome was allograft function. Secondary outcomes included graft and patient survival, acute rejection and parameters of tubular, glomerular and endothelial function. Subgroup analyses were conducted in expanded criteria (ECD) and donation after circulatory (DCD) death donors. RESULTS A total of 101 studies (63 human and 38 animal) were included. There was a lower rate of delayed graft function in recipients with HMP donor grafts compared with CS kidneys (RR 0.77; 95% CI 0.69-0.87). Primary nonfunction (PNF) was reduced in ECD kidneys preserved by HMP (RR 0.28; 95% CI 0.09-0.89). Renal function in animal studies was significantly better in WP kidneys compared with both HMP (standardized mean difference [SMD] of peak creatinine 1.66; 95% CI 3.19 to 0.14) and CS (SMD of peak creatinine 1.72; 95% CI 3.09 to 0.34). MP improves renal preservation through the better maintenance of tubular, glomerular, and endothelial function and integrity. CONCLUSIONS HMP improves short-term outcomes after renal transplantation, with a less clear effect in the longer-term. There is considerable room for modification of the process to assess whether superior outcomes can be achieved through oxygenation, perfusion fluid manipulation, and alteration of perfusion temperature. In particular, correlative experimental (animal) data provides strong support for more clinical trials investigating normothermic MP.
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Affiliation(s)
- Ahmer M. Hameed
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research
- Department of Surgery, Westmead Hospital, Westmead
- Sydney Medical School, University of Sydney, Sydney
| | - Henry C. Pleass
- Department of Surgery, Westmead Hospital, Westmead
- Sydney Medical School, University of Sydney, Sydney
- Department of Surgery, Royal Prince Alfred Hospital, Camperdown
| | - Germaine Wong
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research
- Sydney School of Public Health, University of Sydney
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia
| | - Wayne J. Hawthorne
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research
- Department of Surgery, Westmead Hospital, Westmead
- Sydney Medical School, University of Sydney, Sydney
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26
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Does the Pulsatile Preservation Machine Have Any Impact in the Discard Rate of Kidneys From Older Donors After Brain Death? Transplant Proc 2016; 47:2324-7. [PMID: 26518917 DOI: 10.1016/j.transproceed.2015.08.036] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Donors after brain death (DBD) older than 60 years have become 46.8% of our current activity, with higher risk of renal discard rate (RDR). Assessment of kidney suitability requires complementary strategies: macroscopic evaluation, kidney biopsy score (KBS), and renal hemodynamic evaluation with the Pulsatile Perfusion Machine (PPM). METHODS Descriptive, cross-sectional, comparative study of kidneys procured and RDR, comparing 3 time periods: 2000 to June 2004, when only KBS were used; July 2004 to 2008 (introduction of PPM and learning period); and 2009 to 2013 (experienced use of PPM). Transplantation criteria were KBS <3 and PPM renal resistance <0.4 mm Hg/mL/min and arterial renal flow >70 mL/min. RESULTS Between 2000 and 2013, a 59.2% reduction in DBD kidneys was observed. However, older kidneys had an increase from 33.5% to 46.8%. The RDR had increased, comparing the first to the third period from 25.4% to 38.3%. However, the RDR was lower when kidneys were evaluated with PPM than those evaluated only with KBS and preserved in cold storage (CS) (21.4% versus 43.7%). There was a significant difference in cold ischemia time, because CS kidney was grafted before PPM. During the third period, more kidneys with KBS ≥4 were assigned to PPM. CONCLUSIONS Notwithstanding the decrease in DBD-procured kidneys and the increase in older kidneys during last period, the use of PPM allowed low DR compared with CS. A bias in the results of PPM could be generated when kidneys with higher KBS were excluded from PPM. The use of KBS only to decide acceptance could preclude the use of an additional tool to evaluate suitability.
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van Heurn LWE, Talbot D, Nicholson ML, Akhtar MZ, Sanchez-Fructuoso AI, Weekers L, Barrou B. Recommendations for donation after circulatory death kidney transplantation in Europe. Transpl Int 2015; 29:780-9. [PMID: 26340168 DOI: 10.1111/tri.12682] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 06/19/2015] [Accepted: 08/26/2015] [Indexed: 12/29/2022]
Abstract
Donation after circulatory death (DCD) donors provides an invaluable source for kidneys for transplantation. Over the last decade, we have observed a substantial increase in the number of DCD kidneys, particularly within Europe. We provide an overview of risk factors associated with DCD kidney function and survival and formulate recommendations from the sixth international conference on organ donation in Paris, for best-practice guidelines. A systematic review of the literature was performed using Ovid Medline, Embase and Cochrane databases. Topics are discussed, including donor selection, organ procurement, organ preservation, recipient selection and transplant management.
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Affiliation(s)
| | - David Talbot
- Department of Liver/Renal Transplant, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Michael L Nicholson
- Department of Surgery, NIHR Cambridge Biomedical Research Centre, Cambridge, UK
| | | | | | - Laurent Weekers
- Department of Nephrology-Dialysis-Transplantation, University of Liège, CHU Sart Tilman, Liège, Belgium
| | - Benoit Barrou
- Department of Urology - Transplantation, GHzu Pitié Salpêtriere, Paris, France
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28
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Assessing viability of extracorporeal preserved muscle transplants using external field stimulation: a novel tool to improve methods prolonging bridge-to-transplantation time. Sci Rep 2015; 5:11956. [PMID: 26145230 PMCID: PMC4491708 DOI: 10.1038/srep11956] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 06/11/2015] [Indexed: 02/07/2023] Open
Abstract
Preventing ischemia-related cell damage is a priority when preserving tissue for transplantation. Perfusion protocols have been established for a variety of applications and proven to be superior to procedures used in clinical routine. Extracorporeal perfusion of muscle tissue though cumbersome is highly desirable since it is highly susceptible to ischemia-related damage. To show the efficacy of different perfusion protocols external field stimulation can be used to immediately visualize improvement or deterioration of the tissue during active and running perfusion protocols. This method has been used to show the superiority of extracorporeal perfusion using porcine rectus abdominis muscles perfused with heparinized saline solution. Perfused muscles showed statistically significant higher ability to exert force compared to nonperfused ones. These findings can be confirmed using Annexin V as marker for cell damage, perfusion of muscle tissue limits damage significantly compared to nonperfused tissue. The combination of extracorporeal perfusion and external field stimulation may improve organ conservation research.
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29
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Dion MS, McGregor TB, McAlister VC, Luke PP, Sener A. Hypothermic machine perfusion improves Doppler ultrasonography resistive indices and long-term allograft function after renal transplantation: a single-centre analysis. BJU Int 2015; 116:932-7. [PMID: 25327417 DOI: 10.1111/bju.12960] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVES To evaluate whether hypothermic machine perfusion (HMP) of transplanted kidneys can improve long-term renal allograft function compared with static cold storage (CS). METHODS We evaluated whether graft Doppler ultrasonography resistive indices improved with the use of HMP compared with CS preservation, and examined whether these improvements were predictive of long-term graft function. A total of 30 kidney transplants (15 pairs) were examined. One of the kidney pairs was placed on CS and transplanted first (CS group, n = 15). The other kidney of each pair was placed on HMP and transplanted after the CS group (HMP group, n = 15). Doppler ultrasonography was performed on days 1 and 7 after transplantation and resistive indices were evaluated. The estimated glomerular filtration rate (eGFR) was monitored for 24 months after transplantation. RESULTS Despite longer cold ischaemia times, kidneys maintained with HMP had lower resistive indices (P = 0.005) with correspondingly higher eGFR throughout the follow-up. Subgroup analysis showed that the HMP-induced improvement in postoperative eGFR was greatest in kidneys obtained from donation after cardiac death (DCD), even at 2 years after transplantation (P = 0.008). CONCLUSIONS HMP of transplant kidneys appears to improve vascular resistance after transplantation and has a positive impact on long-term allograft function compared with CS in the population of recipients of DCD kidneys.
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Affiliation(s)
- Marie S Dion
- Department of Surgery, Division of Urology, Western University, London, Ontario, Canada
| | - Thomas B McGregor
- Department of Surgery, Division of Urology, University of Manitoba, Winnepeg, Manitoba, Canada
| | - Vivian C McAlister
- Department of Surgery, Division of Urology, Western University, London, Ontario, Canada.,Multi-Organ Transplant Program, London Health Sciences Center, London, Ontario, Canada
| | - Patrick P Luke
- Department of Surgery, Division of Urology, Western University, London, Ontario, Canada.,Multi-Organ Transplant Program, London Health Sciences Center, London, Ontario, Canada.,Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, London, Ontario, Canada
| | - Alp Sener
- Department of Surgery, Division of Urology, Western University, London, Ontario, Canada.,Department of Microbiology and Immunology, Western University, London, Ontario, Canada.,Center for Human Immunology, Western University, London, Ontario, Canada.,Multi-Organ Transplant Program, London Health Sciences Center, London, Ontario, Canada.,Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, London, Ontario, Canada
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30
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Should Pulsatile Preservation Be the Gold Standard in Kidney Transplantation? CURRENT TRANSPLANTATION REPORTS 2015. [DOI: 10.1007/s40472-015-0063-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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31
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. EXP CLIN TRANSPLANT 2015; 13. [DOI: 10.6002/ect.2014.0174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register]
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32
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. EXP CLIN TRANSPLANT 2015; 13. [DOI: 10.6002/ect.2014.0175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Jochmans I, O'Callaghan JM, Pirenne J, Ploeg RJ. Hypothermic machine perfusion of kidneys retrieved from standard and high-risk donors. Transpl Int 2015; 28:665-76. [PMID: 25630347 DOI: 10.1111/tri.12530] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2014] [Revised: 12/23/2014] [Accepted: 01/22/2015] [Indexed: 01/15/2023]
Abstract
Hypothermic machine perfusion (HMP) of kidneys is a long-established alternative to static cold storage and has been suggested to be a better preservation method. Today, as our deceased donor profile continues to change towards higher-risk kidneys of lower quality, we are confronted with the limits of cold storage. Interest in HMP as a preservation technique is on the rise. Furthermore, HMP also creates a window of opportunity during which to assess the viability and quality of the graft before transplantation. The technology might also provide a platform during which the graft could be actively repaired, making it particularly attractive for higher-risk kidneys. We review the current evidence on HMP in kidney transplantation and provide an outlook for the use of the technology in the years to come.
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Affiliation(s)
- Ina Jochmans
- Department of Microbiology and Immunology, Abdominal Transplantation, KU Leuven - University of Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - John M O'Callaghan
- Nuffield Department of Surgical Sciences, Biomedical Research Centre and Oxford Transplant Centre, University of Oxford, Oxford, UK.,Centre for Evidence in Transplantation, Royal College of Surgeons of England and London School of Hygiene and Tropical Medicine, London, UK
| | - Jacques Pirenne
- Department of Microbiology and Immunology, Abdominal Transplantation, KU Leuven - University of Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Rutger J Ploeg
- Nuffield Department of Surgical Sciences, Biomedical Research Centre and Oxford Transplant Centre, University of Oxford, Oxford, UK
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Jia JJ, Li JH, Jiang L, Lin BY, Wang L, Su R, Zhou L, Zheng SS. Liver protection strategies in liver transplantation. Hepatobiliary Pancreat Dis Int 2015; 14:34-42. [PMID: 25655288 DOI: 10.1016/s1499-3872(15)60332-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Liver transplantation is the therapy of choice for patients with end-stage liver diseases. However, the gap between the low availability of organs and high demand is continuously increasing. Innovative strategies for organ protection are necessary to expand donor pool and to achieve better outcomes for liver transplantation. The present review analyzed and compared various strategies of liver protection. DATA SOURCES Databases such as PubMed, Embase and Ovid were searched for the literature related to donor liver protection strategies using following key words: "ischemia reperfusion injury", "graft preservation", "liver transplantation", "machine perfusion" and "conditioning". Of the 146 studies identified, only those with cutting edge strategies were analyzed. RESULTS A variety of therapeutic approaches were proposed to alleviate graft ischemia/reperfusion injury, which included static cold storage, machine perfusion (hypothermic, normothermic and subnormothermic), manual conditioning (pre, post and remote), and pharmacological conditioning. Evidences from animal experiments and clinical trials suggested that all these strategies could potentially protect liver graft; however, their clinical applications are limited partially due to their own disadvantages. CONCLUSIONS There are a plenty of methods suggested to decrease the degree of donor liver transplantation-related injury. However, none of these approaches is perfect in clinical practice. More translational researches (molecular and clinical studies) are needed to improve the techniques in liver graft protection.
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Affiliation(s)
- Jun-Jun Jia
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Health; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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35
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Nath J, Guy A, Smith TB, Cobbold M, Inston NG, Hodson J, Tennant DA, Ludwig C, Ready AR. Metabolomic perfusate analysis during kidney machine perfusion: the pig provides an appropriate model for human studies. PLoS One 2014; 9:e114818. [PMID: 25502759 PMCID: PMC4264773 DOI: 10.1371/journal.pone.0114818] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Accepted: 10/21/2014] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Hypothermic machine perfusion offers great promise in kidney transplantation and experimental studies are needed to establish the optimal conditions for this to occur. Pig kidneys are considered to be a good model for this purpose and share many properties with human organs. However it is not established whether the metabolism of pig kidneys in such hypothermic hypoxic conditions is comparable to human organs. METHODS Standard criteria human (n = 12) and porcine (n = 10) kidneys underwent HMP using the LifePort Kidney Transporter 1.0 (Organ Recovery Systems) using KPS-1 solution. Perfusate was sampled at 45 minutes and 4 hours of perfusion and metabolomic analysis performed using 1-D 1H-NMR spectroscopy. RESULTS There was no inter-species difference in the number of metabolites identified. Of the 30 metabolites analysed, 16 (53.3%) were present in comparable concentrations in the pig and human kidney perfusates. The rate of change of concentration for 3-Hydroxybutyrate was greater for human kidneys (p<0.001). For the other 29 metabolites (96.7%), there was no difference in the rate of change of concentration between pig and human samples. CONCLUSIONS Whilst there are some differences between pig and human kidneys during HMP they appear to be metabolically similar and the pig seems to be a valid model for human studies.
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Affiliation(s)
- Jay Nath
- Department of Renal Surgery, University Hospitals Birmingham, Birmingham, United Kingdom
- Department of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom
- School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom
- * E-mail:
| | - Alison Guy
- Department of Renal Surgery, University Hospitals Birmingham, Birmingham, United Kingdom
- Department of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom
| | - Thomas B. Smith
- Department of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom
| | - Mark Cobbold
- Department of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom
| | - Nicholas G. Inston
- Department of Renal Surgery, University Hospitals Birmingham, Birmingham, United Kingdom
| | - James Hodson
- Wolfson Computer Laboratory, University Hospitals Birmingham, Birmingham, United Kingdom
| | - Daniel A. Tennant
- School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Christian Ludwig
- Henry Wellcome Building for Biomolecular NMR Spectroscopy, University of Birmingham, Birmingham, United Kingdom
| | - Andrew R. Ready
- Department of Renal Surgery, University Hospitals Birmingham, Birmingham, United Kingdom
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Tozzi M, Franchin M, Soldini G, Ietto G, Chiappa C, Maritan E, Villa F, Carcano G, Dionigi R. Impact of static cold storage VS hypothermic machine preservation on ischemic kidney graft: inflammatory cytokines and adhesion molecules as markers of ischemia/reperfusion tissue damage. Our preliminary results. Int J Surg 2014; 11 Suppl 1:S110-4. [PMID: 24380541 DOI: 10.1016/s1743-9191(13)60029-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
At the present time, deceased heart-beating donor kidney allografts are usually stored cold. Extended-criteria donor (ECD) grafts show higher sensitivity to ischemia-reperfusion damage than standard kidneys. The increasing use of marginal organs in clinical transplantation urgently requires a more effective preservation system. Pulsatile hypothermic machine perfusion has shown major advantages over static cold storage in terms of reduced organ injury during preservation and improved early graft function. This preliminary study aims to compare pulsatile hypothermic machine perfusion and static cold storage of kidney allografts, outlining differences in the levels of early inflammatory cytokines (TNF-α, IL-2 and IL-1β) and soluble intracellular adhesion molecule (sICAM-1) in perfusion and preservation liquid.
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Affiliation(s)
- Matteo Tozzi
- Unit of General Surgery and Organ Transplantation, Insubria University, Varese, Italy; Unit of Vascular Surgery, Circolo teaching Hospital, Insubria University, Varese, Italy
| | - Marco Franchin
- Unit of General Surgery and Organ Transplantation, Insubria University, Varese, Italy; Unit of General Surgery, Circolo teaching Hospital, Insubria University, Varese, Italy
| | - Gabriele Soldini
- Unit of General Surgery and Organ Transplantation, Insubria University, Varese, Italy; Unit of General Surgery, Circolo teaching Hospital, Insubria University, Varese, Italy
| | - Giuseppe Ietto
- Unit of General Surgery and Organ Transplantation, Insubria University, Varese, Italy; Unit of General Surgery, Circolo teaching Hospital, Insubria University, Varese, Italy
| | - Corrado Chiappa
- Unit of General Surgery and Organ Transplantation, Insubria University, Varese, Italy; Unit of General Surgery, Circolo teaching Hospital, Insubria University, Varese, Italy
| | - Emanuele Maritan
- Unit of General Surgery and Organ Transplantation, Insubria University, Varese, Italy; Unit of Vascular Surgery, Circolo teaching Hospital, Insubria University, Varese, Italy
| | - Francesca Villa
- Unit of General Surgery and Organ Transplantation, Insubria University, Varese, Italy; Unit of Vascular Surgery, Circolo teaching Hospital, Insubria University, Varese, Italy
| | - Giulio Carcano
- Unit of General Surgery and Organ Transplantation, Insubria University, Varese, Italy; Unit of General Surgery, Circolo teaching Hospital, Insubria University, Varese, Italy
| | - Renzo Dionigi
- Unit of General Surgery, Circolo teaching Hospital, Insubria University, Varese, Italy
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Use of a pulsatile perfusion pump for renal autotransplantation in a patient undergoing thoracoabdominal bypass for malignant hypertension secondary to Takayasu arteritis. Ann Vasc Surg 2014; 28:1793.e11-4. [PMID: 24698771 DOI: 10.1016/j.avsg.2014.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Revised: 03/19/2014] [Accepted: 03/22/2014] [Indexed: 11/23/2022]
Abstract
Aortorenal bypass is an effective and durable therapy for autoimmune-induced renovascular hypertension. However, when technical and patient factors preclude this option, renal autotransplantation can be a viable alternative. We present a 32-year-old woman who underwent aortobi-iliac bypass with left renal autotransplantation for malignant hypertension secondary to Takayasu arteritis. This is the first description of using machine preservation with a continuous pulsatile perfusion pump to maintain renal preservation before reimplantation. Our method proved safe to the patient and allowed for protection of the organ from prolonged warm ischemia and intraoperative hypoperfusion during a complex reconstruction.
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38
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Bruns H, Schemmer P. Machine perfusion in solid organ transplantation: where is the benefit? Langenbecks Arch Surg 2014; 399:421-427. [PMID: 24429900 DOI: 10.1007/s00423-014-1161-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2013] [Accepted: 01/01/2014] [Indexed: 12/26/2022]
Abstract
BACKGROUND Machine perfusion (MP) in solid organ transplantation has been a topic of variable importance for decades. At the dawn of organ transplantation, MP was one of the standard techniques for preservation; today's gold standard for organ preservation for transplantation is cold storage (CS). The outcome after transplantation of solid organs has tremendously improved over the last five decades. MP has been continuously under investigation and may be an option for organ preservation in selected cases; however, there is only little evidence from clinical trials that can be used to advocate for MP as a routine organ preservation method. METHODS This article reviews the current knowledge on MP in the field of solid organ transplantation with special focus on findings from clinical trials. CONCLUSION Especially in heart and lung transplantation, MP seems to be a promising tool to improve postoperative outcome, but a general evidence-based recommendation for or against an application of MP cannot be given due to the lack of the highest level of clinical evidence. Gold standards such as CS should not be left behind without good reason. Randomized clinical trials are desperately needed to further improve outcome and for better understanding of the underlying pathophysiological mechanisms.
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Affiliation(s)
- Helge Bruns
- Department of General and Transplant Surgery, Ruprecht Karls University, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
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Wszola M, Kwiatkowski A, Domagala P, Wirkowska A, Bieniasz M, Diuwe P, Kieszek R, Durlik M, Chmura A. Preservation of Kidneys by Machine Perfusion Influences Gene Expression and May Limit Ischemia/Reperfusion Injury. Prog Transplant 2014; 24:19-26. [DOI: 10.7182/pit2014384] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Context Machine perfusion improves graft survival. Histopathologic analysis reveals a lower incidence of chronic rejection and interstitial fibrosis in kidneys preserved with machine perfusion. Ischemic/reperfusion injury may help to explain these findings. Objective To assess the activation of genes correlated with ischemic/reperfusion injury in kidneys preserved under different conditions before transplant. Design/Patients Between 2005 and 2006, 69 kidney biopsy specimens were collected and patients were followed up for 5 years after that. Intervention Before transplant, kidneys were preserved with machine perfusion or cold storage. Donors from the machine perfusion and cold storage groups did not differ with regard to age, sex, or hemodynamic status. Recipients were divided into 5 groups: expanded criteria donor–machine perfusion (n = 16), standard criteria donor–machine perfusion (n = 10), expanded criteria donor–cold storage (n = 9), and standard criteria donor–cold storage (n = 27); 7 kidneys were retrieved from living related donors. Main Outcome Measures Biopsies were done 30 minutes after reperfusion. Interleukin-1β, vascular endothelial growth factor, heme oxygenase-1, and hypoxia-inducible factor–1 gene expression levels were analyzed. Results Mean expression levels of hypoxia-inducible factor–1α were significantly higher in the cold storage groups, and lower in the machine perfusion and living-related donor groups. Five-year graft survival was significantly ( P < .05) lower in the expanded criteria donor–cold storage group (66%) than in the standard criteria donor–machine perfusion group (90%). Machine perfusion influences gene expression related to hypoxia during reperfusion and may improve the long-term results of kidney transplant.
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Desai KK, Mora-Esteves C, Holland BK, Dikdan G, Fisher A, Wilson DJ, Koneru B. Does Liver Ischemic Preconditioning in Brain Death Donors Induce Kidney Preconditioning? A Retrospective Analysis. Transplantation 2014; 97:337-43. [DOI: 10.1097/01.tp.0000436926.30897.56] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Abstract
Brain death is associated with complex physiologic changes that may impact the management of the potential organ donor. Medical management is critical to actualizing the individual or family’s intent to donate and maximizing the benefit of that intent. This interval of care in the PICU begins with brain death and consent to donation and culminates with surgical organ procurement. During this phase, risks for hemodynamic instability and compromise of end organ function are high. The brain dead organ donor is in a distinct and challenging pathophysiologic condition that culminates in multifactorial shock. The potential benefits of aggressive medical management of the organ donor may include increased number of donors providing transplantable organs and increased number of organs transplanted per donor. This may improve graft function, graft survival, and patient survival in those transplanted. In this chapter, pathophysiologic changes occurring after brain death are reviewed. General and organ specific donor management strategies and logistic considerations are discussed. There is a significant opportunity for enhancing donor multi-organ function and improving organ utilization with appropriate PICU management.
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Catena F, Coccolini F, Montori G, Vallicelli C, Amaduzzi A, Ercolani G, Ravaioli M, Del Gaudio M, Schiavina R, Brunocilla E, Liviano G, Feliciangeli G, Pinna A. Kidney Preservation: Review of Present and Future Perspective. Transplant Proc 2013; 45:3170-7. [DOI: 10.1016/j.transproceed.2013.02.145] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2011] [Revised: 01/05/2013] [Accepted: 02/16/2013] [Indexed: 01/31/2023]
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Oxygen consumption during oxygenated hypothermic perfusion as a measure of donor organ viability. ASAIO J 2013; 59:427-32. [PMID: 23820283 DOI: 10.1097/mat.0b013e318292e865] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Hypothermic machine perfusion (HMP) for the preservation of kidneys, recovered from extended criteria organ donors (ECDs), presents the opportunity for assessing ex vivo parameters that may have value in predicting postimplantation organ viability. Organ perfusion and vascular resistance are the parameters most frequently cited as the basis for the decision to use or discard a donor kidney. The limitation of these measures is emphasized by the observation that a significant percentage of ECD kidneys with poor perfusion parameters can provide life-sustaining function after transplantation. It has been suggested that whole organ oxygen consumption (OC) during oxygenated HMP may better reflect the proportion of viable tissue in the organ and more reliably predict posttransplant organ function. Our study correlates renal OC and renal vascular resistance (RVR) during oxygenated HMP with postpreservation glomerular filtration rates (GFRs) in rodent kidneys after 24 hours of oxygenated HMP. Kidneys from adult rodents were preserved for 24 hours using oxygenated HMP and static cold storage (SCS). During oxygenated HMP preservation, organ OC, renal organ flow rates, and RVR were serially measured. After the preservation period, organs were mounted onto a Langendorff device for warming to normal body temperature and measurement of GFR. Oxygen consumption and RVR during HMP were correlated with postpreservation GFR. Oxygen consumption during oxygenated HMP was significantly correlated (r2 = 0.871; p < 0.05) with postpreservation GFR, suggesting that higher OC predicts better postpreservation GFR. In contrast, RVR was poorly correlated with postpreservation GFR (r2 = 0.258; p = 0.199). Glomerular filtration rate in SCS kidneys was 0.002 ± 0.003 ml/min/g. We demonstrate that measurement of organ OC during oxygenated HMP may have significant value in predicting postpreservation organ function.
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O'Callaghan JM, Morgan RD, Knight SR, Morris PJ. Systematic review and meta-analysis of hypothermic machine perfusion versus static cold storage of kidney allografts on transplant outcomes. Br J Surg 2013; 100:991-1001. [PMID: 23754643 DOI: 10.1002/bjs.9169] [Citation(s) in RCA: 111] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2012] [Revised: 05/08/2012] [Accepted: 04/11/2013] [Indexed: 02/05/2023]
Abstract
BACKGROUND Adequate preservation of renal allografts for transplantation is important for maintaining and improving transplant outcomes. There are two prevalent methods: hypothermic machine perfusion and static cold storage. The preferred method of storage, however, remains controversial. The objective was to review systematically the evidence comparing outcomes from these two modalities. METHODS A literature search was performed using MEDLINE, Embase, the Cochrane Library, the Transplant Library and the International Clinical Trials Registry Platform. The final date for searches was 30 November 2012. Studies were assessed for methodological quality. Summary effects were calculated as relative risk (RR) with 95 per cent confidence interval (c.i.). Randomized clinical trials (RCTs) and non-RCTs were included, but evaluated separately. Results from RCTs alone were used for meta-analysis. RESULTS Eighteen studies met the inclusion criteria, including seven RCTs (1475 kidneys) and 11 non-RCTs (728 kidneys). The overall risk of delayed graft function was lower with hypothermic machine perfusion than static cold storage (RR 0·81, 95 per cent c.i. 0·71 to 0·92; P = 0·002). There was no difference in the rate of primary non-function (RR 1·15, 0·46 to 2·90; P = 0·767). There was a faster initial fall in the level of serum creatinine with hypothermic machine perfusion in two RCTs, but not in another. There was no relationship between rates of acute rejection or patient survival and the method of preservation. CONCLUSION Data from the included studies suggest that hypothermic machine perfusion reduces delayed graft function compared with static cold storage. There was no difference in primary non-function, acute rejection, long-term renal function or patient survival. A difference in renal graft survival is uncertain.
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Affiliation(s)
- J M O'Callaghan
- Centre for Evidence in Transplantation, Royal College of Surgeons of England and London School of Hygiene and Tropical Medicine, University of London, London, UK.
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Cavaillé-Coll M, Bala S, Velidedeoglu E, Hernandez A, Archdeacon P, Gonzalez G, Neuland C, Meyer J, Albrecht R. Summary of FDA workshop on ischemia reperfusion injury in kidney transplantation. Am J Transplant 2013; 13:1134-48. [PMID: 23566221 DOI: 10.1111/ajt.12210] [Citation(s) in RCA: 112] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Revised: 01/24/2013] [Accepted: 01/31/2013] [Indexed: 01/25/2023]
Abstract
The Food and Drug Administration (FDA) held an open public workshop in September 2011 to discuss the current state of science related to the effects of ischemia reperfusion injury (IRI) on outcomes in kidney transplantation. Topics included the development of IRI and delayed graft function (DGF), histology and biomarkers, donor factors, recipient factors, organ quality and organ preservation by means of cold storage solutions or machine perfusion. Various mechanisms of injury and maladaptive response to IRI were discussed as potential targets of intervention. Animal models evaluating specific pathophysiological pathways were presented, as were the limitations of extrapolating animal results to humans. Clinical trials of various drug products administered in the peri-transplant period were summarized; a few demonstrated early improvements in DGF, but none demonstrated an improvement in late graft function. Clinical trial design for IRI and DGF were also discussed.
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Affiliation(s)
- M Cavaillé-Coll
- Division of Transplant and Ophthalmology Products, Office of Antimicrobial Products, Office of New Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, USA
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Müller S, Constantinescu MA, Kiermeir DM, Gajanayake T, Bongoni AK, Vollbach FH, Meoli M, Plock J, Jenni H, Banic A, Rieben R, Vögelin E. Ischemia/reperfusion injury of porcine limbs after extracorporeal perfusion. J Surg Res 2013; 181:170-82. [DOI: 10.1016/j.jss.2012.05.088] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2012] [Revised: 05/17/2012] [Accepted: 05/31/2012] [Indexed: 02/01/2023]
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Machine perfusion versus cold storage of kidneys derived from donation after cardiac death: a meta-analysis. PLoS One 2013; 8:e56368. [PMID: 23536758 PMCID: PMC3594243 DOI: 10.1371/journal.pone.0056368] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2012] [Accepted: 01/08/2013] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND In response to the increased organ shortage, organs derived from donation after cardiac death (DCD) donors are becoming an acceptable option once again for clinical use in transplantation. However, transplant outcomes in cases where DCD organs are used are not as favorable as those from donation after brain death or living donors. Different methods of organ preservation are a key factor that may influence the outcomes of DCD kidney transplantation. METHODS We compared the transplant outcomes in patients receiving DCD kidneys preserved by machine perfusion (MP) or by static cold storage (CS) preservation by conducting a meta-analysis. The MEDLINE, EMBASE and Cochrane Library databases were searched. All studies reporting outcomes for MP versus CS preserved DCD kidneys were further considered for inclusion in this meta-analysis. Odds ratios and 95% confidence intervals (CI) were calculated to compare the pooled data between groups that were transplanted with kidneys that were preserved by MP or CS. RESULTS Four prospective, randomized, controlled trials, involving 175 MP and 176 CS preserved DCD kidney transplant recipients, were included. MP preserved DCD kidney transplant recipients had a decreased incidence of delayed graft function (DGF) with an odd ration of 0.56 (95% CI = 0.36-0.86, P = 0.008) compared to CS. However, no significant differences were seen between the two technologies in incidence of primary non-function, one year graft survival, or one year patient survival. CONCLUSIONS MP preservation of DCD kidneys is superior to CS in terms of reducing DGF rate post-transplant. However, primary non-function, one year graft survival, and one year patient survival were not affected by the use of MP or CS for preservation.
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Hypothermic machine perfusion in deceased donor kidney transplantation: a systematic review. J Surg Res 2012; 180:176-82. [PMID: 23211958 DOI: 10.1016/j.jss.2012.10.055] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2012] [Revised: 10/05/2012] [Accepted: 10/26/2012] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hypothermic machine perfusion (HMP) of kidneys is intended to mitigate the deleterious effects of cold storage on organ quality, particularly when the cold ischemic time is prolonged or the donor is otherwise marginal. The use of HMP has remained controversial; however, a number of randomized controlled trials (RCTs) have recently been conducted to clarify its benefits. METHODS We undertook a systematic search of the Medline and Embase databases and of the Cochrane Central Register of Controlled Trials. We included only RCTs in the meta-analysis. Outcomes analyzed were the incidence of delayed graft function (DGF), primary nonfunction (PNF), graft loss, and patient death at 1 y. RESULTS We identified seven RCT trials and subjected them to meta-analysis, including 1353 kidney transplant recipients. Hypothermic machine perfusion significantly reduced the incidence of DGF (risk ratio [RR] 0.83, 95% confidence interval [CI] 0.72-0.96). There was no difference in the incidence of PNF (RR 0.78, 95% CI 0.36-1.68), graft loss at 1 y (RR 0.87, 95% CI 0.64-1.19), and patient death at 1 y (RR 0.91, 95% CI 0.60-1.37) between HMP and donor kidneys preserved using cold storage. CONCLUSIONS There are few RCT comparing HMP and cold storage of kidneys in deceased donor kidney transplantation. Although these studies are small and heterogeneous in design, HMP appeared to be associated with a reduced incidence of DGF. No difference in the incidence of PNF, graft loss, or patient death at 1 y could be demonstrated.
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Lodhi SA, Lamb KE, Uddin I, Meier-Kriesche HU. Pulsatile pump decreases risk of delayed graft function in kidneys donated after cardiac death. Am J Transplant 2012; 12:2774-80. [PMID: 22823748 DOI: 10.1111/j.1600-6143.2012.04179.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Organ storage techniques have been under scrutiny to determine the best preservation method, particularly in donation after cardiac death (DCD) kidneys. Conflicting literature on the benefit of pulsatile perfusion (PP) over cold storage (CS) warrants further investigation. We analyzed the risk of developing delayed graft function (DGF) in recipients of DCD and donation after brain death (DBD) kidneys undergoing PP or CS. We stratified on basis of cold ischemic time (CIT) to determine the interaction of preservation techniques, CIT and DCD kidneys on developing DGF. Of 54 136 recipients, 4923 received DCD kidneys of which 3330 (67%) underwent PP. Of 49 213 DBD recipients, 7531 (15%) underwent PP. DCD had a higher risk of DGF versus DBD (adjusted odds ratio, AOR 3.2; 3.0-3.5). PP kidneys had less DGF (AOR 0.59; 0.56-0.63) compared to CS. Interaction models of method by donor type referenced to PP/DBD revealed CS/DBD kidneys had higher DGF (AOR 1.8; 1.7-1.9), whereas CS/DCD kidneys had the highest risk of DGF (AOR 5.01; 4.43-5.67). Even though suggestive for a benefit of PP on DGF, this retrospective analysis cannot address whether this is an intrinsic effect of PP or is associated with the logistics of PP such as discard of DCD kidneys based on pump parameters.
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Affiliation(s)
- S A Lodhi
- Division of Nephrology, Department of Medicine, Hypertension and Solid Organ Transplant, University of Florida, Gainesville, FL, USA
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Review of Randomized Clinical Trials of Donor Management and Organ Preservation in Deceased Donors. Transplantation 2012; 94:425-41. [DOI: 10.1097/tp.0b013e3182547537] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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