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Elec FI, Moisoiu T, Negrut MF, Simon R, Elec AD, Muntean AM, Horciag G, Sitaru AM, Rachisan AL, Oniscu G, Antal O. Validation of Kidney Donor Profile Index and Estimated Post-Transplant Survival Scores in an Eastern European Transplantation Center-A Seven-Year Retrospective Observational Study. J Clin Med 2025; 14:3540. [PMID: 40429534 PMCID: PMC12112181 DOI: 10.3390/jcm14103540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2025] [Revised: 05/06/2025] [Accepted: 05/14/2025] [Indexed: 05/29/2025] Open
Abstract
Background/Objectives: The Kidney Donor Profile Index (KDPI) is an important metric for evaluating the quality of donor kidneys and predicting post-transplant outcomes. The Estimated Post-Transplant Survival (EPTS) score is a tool for estimating kidney transplant candidates' long-term survival. However, their validity in Eastern European cohorts is yet to be explored. This study aimed to evaluate the predictive accuracy of the KDPI and EPTS in a local cohort. Methods: We conducted a seven-year retrospective observational study at a high-volume transplant center in Romania. Data from 353 patients who received kidney transplants from brain-dead donors (DBDs) between 2017 and 2023 were analyzed. The KDPI scores were stratified into <35%, 35-85%, and >85%, while EPTS was stratified into <20%, 20-60%, and >60%. Primary outcomes included one-, three-, and five-year post-transplant graft function as estimated by eGFR, while secondary outcomes involved patient and graft survival rates at one, three, and five years. Results: Graft function and survival rates were significantly lower with increasing KDPI and EPTS scores, reinforcing the utility of both scores in clinical decision-making. Conclusions: Despite their limitations, KDPI and EPTS remain valuable predictors in our patient population.
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Affiliation(s)
- Florin Ioan Elec
- Clinical Institute of Urology and Renal Transplantation, 400006 Cluj-Napoca, Romania; (F.I.E.); (T.M.); (R.S.); (A.D.E.); (A.M.M.); (G.H.); (O.A.)
- Department of Urology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Tudor Moisoiu
- Clinical Institute of Urology and Renal Transplantation, 400006 Cluj-Napoca, Romania; (F.I.E.); (T.M.); (R.S.); (A.D.E.); (A.M.M.); (G.H.); (O.A.)
- Department of Urology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- Biomed Data Analytics SRL, 400696 Cluj-Napoca, Romania
| | - Matei Florin Negrut
- Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Robert Simon
- Clinical Institute of Urology and Renal Transplantation, 400006 Cluj-Napoca, Romania; (F.I.E.); (T.M.); (R.S.); (A.D.E.); (A.M.M.); (G.H.); (O.A.)
- Department of Anaesthesia and Intensive Care, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- Doctoral School, Faculty of Medicine, University of Oradea, 410073 Oradea, Romania
| | - Alina Daciana Elec
- Clinical Institute of Urology and Renal Transplantation, 400006 Cluj-Napoca, Romania; (F.I.E.); (T.M.); (R.S.); (A.D.E.); (A.M.M.); (G.H.); (O.A.)
| | - Adriana Milena Muntean
- Clinical Institute of Urology and Renal Transplantation, 400006 Cluj-Napoca, Romania; (F.I.E.); (T.M.); (R.S.); (A.D.E.); (A.M.M.); (G.H.); (O.A.)
| | - Georgeta Horciag
- Clinical Institute of Urology and Renal Transplantation, 400006 Cluj-Napoca, Romania; (F.I.E.); (T.M.); (R.S.); (A.D.E.); (A.M.M.); (G.H.); (O.A.)
| | - Ana Maria Sitaru
- Department of Pediatrics, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Andreea Liana Rachisan
- Department of Mother and Child, Discipline of Pediatrics II, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Gabriel Oniscu
- Transplantation Surgery Division, Department of Clinical Science Intervention and Technology, Karolinska Institute, 141 86 Huddinge, Sweden;
| | - Oana Antal
- Clinical Institute of Urology and Renal Transplantation, 400006 Cluj-Napoca, Romania; (F.I.E.); (T.M.); (R.S.); (A.D.E.); (A.M.M.); (G.H.); (O.A.)
- Department of Anaesthesia and Intensive Care, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
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Kawamura M, Matsumura S, Abe T, Kobayashi Y, Fukae S, Tanaka R, Taniguchi A, Nakazawa S, Yamanaka K, Kato T, Namba-Hamano T, Kobayashi H, Nonomura N, Kakuta Y, Imamura R. A novel Si-based antioxidant agent attenuates antibody-mediated rejection in allogeneic rat kidney transplantation. Am J Transplant 2025; 25:943-953. [PMID: 39848340 DOI: 10.1016/j.ajt.2025.01.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 01/17/2025] [Accepted: 01/17/2025] [Indexed: 01/25/2025]
Abstract
Antibody-mediated rejection remains a leading cause of graft loss during kidney transplantation. Ischemia reperfusion injury (IRI) has been reported to promote T cell proliferation, leading to B cell activation and subsequent production of donor-specific antibodies, which target antigens on the vascular endothelium. We hypothesize that a novel therapeutic strategy targeting highly toxic reactive oxygen species could mitigate oxidative stress and immune responses associated with IRI. Our previous study demonstrated that oral administration of a silicon (Si)-based agent consistently generates substantial amounts of hydrogen, effectively suppressing IRI-induced oxidative stress and acute kidney injury in a rat renal clamp model. Here, we investigated the effect of the Si-based agent on immune responses in an allogeneic kidney transplant setting. Using both short-term and long-term evaluation models, we found that the Si-based agent suppressed oxidative stress and acquired immunity activation. Furthermore, early suppression of donor-specific antibody production and amelioration of chronic antibody-mediated rejection were observed. These findings indicate that the Si-based agent offers protective effects on graft function and survival, highlighting its potential clinical application to improve outcomes for kidney transplant recipients.
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Affiliation(s)
- Masataka Kawamura
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan; Department of Urology, Osaka General Medical Center, Osaka, Japan
| | - Soichi Matsumura
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Toyofumi Abe
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan; Department of Urology, Sumitomo Hospital, Osaka, Japan.
| | - Yuki Kobayashi
- The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Japan
| | - Shota Fukae
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryo Tanaka
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ayumu Taniguchi
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Shigeaki Nakazawa
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Kazuaki Yamanaka
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Taigo Kato
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Tomoko Namba-Hamano
- Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hikaru Kobayashi
- The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Japan
| | - Norio Nonomura
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yoichi Kakuta
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryoichi Imamura
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan; Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
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Chumdermpadetsuk RR, Alvino DML, Kaul S, Fleishman A, Eckhoff DE, Pavlakis M, Lee DD. Impact of Donor Warm Ischemia Time on Graft Survival for Donation After Circulatory Death Kidney Transplantation. Transplantation 2025; 109:504-510. [PMID: 39049132 DOI: 10.1097/tp.0000000000005155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/27/2024]
Abstract
BACKGROUND The utilization of kidneys donated after circulatory death (DCD) is an important strategy to address the ongoing shortage of organs suitable for transplantation in the United States. However, the nonuse rate of DCD kidneys remains high compared with kidneys donated after brain death (DBD) because of concerns regarding the injury incurred during donor warm ischemia time (DWIT). Therefore, we investigated the impact of DWIT on the risk of death-censored graft failure after DCD kidney transplantation (KT). METHODS Retrospective analysis was conducted on DCD KTs using the Standard Transplant Analysis and Research data set. The association of DWIT with death-censored graft failure was evaluated using multivariable Cox proportional hazard regression, with reference to DCD KTs with Kidney Donor Risk Index (KDRI) of ≤0.78 and the median DWIT of 26 min. RESULTS A total of 28 032 DCD kidney-alone transplants between January 2010 and December 2021 were studied. When stratified by KDRI, increasing DWIT was associated with a clinically significant increased risk for death-censored graft failure only in the subset of kidneys with KDRI >1.14 but not in those with KDRI >0.78-≤0.94 and >0.94-≤1.14, compared with the reference group. CONCLUSIONS We suggest that clinicians should not decline kidneys on the basis of DWIT in favor of potential offers of DBD or other DCD kidneys with shorter DWIT, provided that their KDRI scores are within an acceptable limit. Our study highlights opportunities for more efficient usage of DCD kidneys and improving the shortage of transplantable organs.
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Affiliation(s)
- Ritah R Chumdermpadetsuk
- Division of Transplantation, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA
| | | | - Sumedh Kaul
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA
| | - Aaron Fleishman
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA
| | - Devin E Eckhoff
- Division of Transplantation, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA
| | - Martha Pavlakis
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | - David D Lee
- Division of Transplantation, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA
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Stratta RJ, Harriman DI. Does Anybody Really Know What (Warm Ischemia) Time It Is? Transplantation 2025; 109:e146-e147. [PMID: 39049085 DOI: 10.1097/tp.0000000000005154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/27/2024]
Affiliation(s)
- Robert J Stratta
- Department of Surgery, Section of Abdominal Organ Transplantation, Atrium Health Wake Forest Baptist, Winston-Salem, NC
| | - David I Harriman
- Department of Urology, University of British Columbia, Vancouver, BC, Canada
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Oh S, Kim K, Na O, Ha J, Koo TY, Yang J. Evaluating non-utilization of deceased donor kidneys in Korea. Sci Rep 2025; 15:2588. [PMID: 39833548 PMCID: PMC11746993 DOI: 10.1038/s41598-025-86998-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 01/15/2025] [Indexed: 01/22/2025] Open
Abstract
Considering the low deceased donation rates despite increasing rates of end-stage kidney disease in Asia, minimizing donor kidney discard is important. This study aimed to investigate the current situation of donor kidney discard in Korea. This nationwide study included deceased donor kidneys of candidates for kidney transplantation (KT) between 2013 and 2018 in Korea. Kidney discard was defined as no procurement or discarding after procurement of kidneys. Among 5592 deceased donor kidneys, no-procurement, single-procurement, and double-procurement were 385, 63, and 5144, respectively. All unilaterally procured kidneys, except for one, were transplanted. Bilaterally procured kidneys were accompanied by two KT (n = 5058), one KT with the other kidney discarded (n = 33), or both kidneys discarded (n = 20). The overall kidney discard rate was 7.9%. The cause of non-procurement was universally organ damage, and the common causes of kidney discard after procurement were organ damage, absence of available candidates, and malignancy. While the kidney donor profile index was higher in the discarded group than in the KT group, a large overlap was observed. The risk factors for kidney non-utilization were old age, hypertension, diabetes mellitus, high serum creatinine levels, low hemoglobin levels, and non-cerebrovascular causes of death. KT using contralateral kidney in the discard group showed graft failure and mortality rates comparable to those of KT in the no-discard group. The discard rate of deceased donor kidneys was low, and the discard of one kidney does not necessarily rule out the utilization of contralateral kidney, especially in Korea with a long waiting time.
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Affiliation(s)
- Suhyun Oh
- Division of Nephrology, Department of Internal Medicine, College of Medicine, Yonsei University Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Keonhwa Kim
- Division of Nephrology, Department of Internal Medicine, College of Medicine, Yonsei University Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Omi Na
- Division of Nephrology, Department of Internal Medicine, College of Medicine, Yonsei University Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Juhyung Ha
- Division of Nephrology, Department of Internal Medicine, College of Medicine, Yonsei University Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Tai Yeon Koo
- Department of Nephrology, Korea University Anam Hospital, Seoul, Republic of Korea
| | - Jaeseok Yang
- Division of Nephrology, Department of Internal Medicine, College of Medicine, Yonsei University Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
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Savoye E, Martin-Lefèvre L, Dantal J, Dorez D, Gaudez F, Drouin S, Riou B, Strecker G, Thierry A, Legeai C, Bronchard R, Kerbaul F, Antoine C. Risk Factors for Adverse Outcomes in Kidney Transplants From Donors After Circulatory Death With Normothermic Regional Perfusion: A Systematic Analysis. Transplantation 2024; 108:e417-e427. [PMID: 38872246 DOI: 10.1097/tp.0000000000005102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2024]
Abstract
BACKGROUND This study examined 1071 adult primary kidney transplants from the French-controlled donation after the circulatory determination of death (cDCD) program, which uses normothermic regional perfusion (NRP), and involves short cold ischemia times (CIT) and constrained asystole times differing by donor age. METHODS Logistic regression identified risk factors for primary nonfunction (PNF), delayed graft function (DGF), and graft failure. RESULTS Risk factors for PNF included donor hypertension, admission for ischemic vascular stroke, and HLA DR mismatches. Risk factors for DGF included functional warm ischemia time >40 min, dialysis >2 y, recipient body mass index of 30 kg/m 2 or higher, recipient diabetes, and CIT >10 h. Risk factors for 1-y graft failure included donor hypertension, donor lung recovery, ostial calcification, recipient cardiovascular comorbidities, and HLA DR mismatches. A high donor estimated glomerular filtration rate protected against DGF and graft failure at 1-y. After adjustment restricted to recipient and graft factors and donor age, the risks of PNF, DGF, and graft failure increased with donor age up to 65 y and then remained stable. CONCLUSIONS The study suggests that cDCD kidney transplants are highly successful, but also that its outcomes are influenced by lung recovery, poor HLA DR matching, and warm ischemia times differing with donor age. Our study identified several risk factors for kidney transplantation failure after cDCD with systematic use of NRP and some of them seem as modifiable variables associated with cDCD transplant outcome.
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Affiliation(s)
- Emilie Savoye
- Agence de la biomédecine, Direction Prélèvement Greffe Organes-Tissus, 93212 Saint-Denis-la-Plaine cedex, France
| | - Laurent Martin-Lefèvre
- Organ Donation Service, Service de Médecine Intensive Réanimation, La Roche-Sur-Yon, France
| | - Jacques Dantal
- Nephrology and Transplantation Department, Centre Hospitalier Universitaire, Nantes, France
| | - Didier Dorez
- Organ Donation Service, Centre Hospitalier Annecy-genevois, Epagny Metz-Tessy, France
| | - François Gaudez
- Department of Urology, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Sarah Drouin
- Kidney Transplantation, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Bruno Riou
- Sorbonne Université, UMR 1166, IHU ICAN, Organs and Tissues Harvesting Unit, Hôpital de la Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France
| | | | - Antoine Thierry
- Department of Nephrology, University of Poitiers, Poitiers, France
| | - Camille Legeai
- Agence de la biomédecine, Direction Prélèvement Greffe Organes-Tissus, 93212 Saint-Denis-la-Plaine cedex, France
| | - Régis Bronchard
- Agence de la biomédecine, Direction Prélèvement Greffe Organes-Tissus, 93212 Saint-Denis-la-Plaine cedex, France
| | - François Kerbaul
- Agence de la biomédecine, Direction Prélèvement Greffe Organes-Tissus, 93212 Saint-Denis-la-Plaine cedex, France
| | - Corinne Antoine
- Agence de la biomédecine, Direction Prélèvement Greffe Organes-Tissus, 93212 Saint-Denis-la-Plaine cedex, France
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Ayorinde JO, Loizeau X, Bardsley V, Thomas SA, Romanchikova M, Samoshkin A, Pettigrew GJ. Measurement Matters: A Metrological Approach to Renal Preimplantation Biopsy Evaluation to Address Uncertainty in Organ Selection. Transplant Direct 2024; 10:e1708. [PMID: 39399062 PMCID: PMC11469905 DOI: 10.1097/txd.0000000000001708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 07/07/2024] [Accepted: 07/23/2024] [Indexed: 10/15/2024] Open
Abstract
Background Preimplantation biopsy combines measurements of injury into a composite index to inform organ acceptance. The uncertainty in these measurements remains poorly characterized, raising concerns variability may contribute to inappropriate clinical decisions. Methods We adopted a metrological approach to evaluate biopsy score reliability. Variability was assessed by performing repeat biopsies (n = 293) on discarded allografts (n = 16) using 3 methods (core, punch, and wedge). Uncertainty was quantified using a bootstrapping analysis. Observer effects were controlled by semi-blinded scoring, and the findings were validated by comparison with standard glass evaluation. Results The surgical method strongly determined the size (core biopsy area 9.04 mm2, wedge 37.9 mm2) and, therefore, yield (glomerular yield r = 0.94, arterial r = 0.62) of each biopsy. Core biopsies yielded inadequate slides most frequently. Repeat biopsy of the same kidney led to marked variation in biopsy scores. In 10 of 16 cases, scores were contradictory, crossing at least 1 decision boundary (ie, to transplant or to discard). Bootstrapping demonstrated significant uncertainty associated with single-slide assessment; however, scores were similar for paired kidneys from the same donor. Conclusions Our investigation highlights the risks of relying on single-slide assessment to quantify organ injury. Biopsy evaluation is subject to uncertainty, meaning each slide is better conceptualized as providing an estimate of the kidney's condition rather than a definitive result. Pooling multiple assessments could improve the reliability of biopsy analysis, enhancing confidence. Where histological quantification is necessary, clinicians should seek to develop new protocols using more tissue and consider automated methods to assist pathologists in delivering analysis within clinical time frames.
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Affiliation(s)
- John O.O. Ayorinde
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
| | - Xavier Loizeau
- National Physical Laboratory, Teddington, United Kingdom
| | - Victoria Bardsley
- Department of Histopathology, Addenbrooke’s Hospital, Cambridge, United Kingdom
| | | | | | - Alex Samoshkin
- Office for Translational Research, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Gavin J. Pettigrew
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
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Zhang R, Trotter PB, McCaffrey J, Fitzroy R, Trivioli G, Stewart BJ, Ferdinand JR, Loudon KW, Riding A, West J, Ferro A, Clatworthy MR. Assessment of biological organ age using molecular pathology in pre-transplant kidney biopsies. Kidney Int 2024; 106:302-316. [PMID: 38692408 DOI: 10.1016/j.kint.2024.03.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 01/21/2024] [Accepted: 03/18/2024] [Indexed: 05/03/2024]
Abstract
Organ shortage is a major challenge in kidney transplantation but the use of older donors, often with co-morbidities, is hampered by inconsistent outcomes. Methods of accurately stratifying marginal donor organs by clinical and histological assessment are lacking. To better understand organ variability, we profiled the transcriptomes of 271 kidneys from deceased donors at retrieval. Following correction for biopsy composition, we assessed molecular pathways that associated with delayed, and sub-optimal one-year graft function. Analysis of cortical biopsies identified an adaptive immune gene-rich module that significantly associated with increasing age and worse outcomes. Cellular deconvolution using human kidney reference single cell transcriptomes confirmed an increase in kidney-specific B and T cell signatures, as well as kidney macrophage, myofibroblast and fibroblast gene sets in this module. Surprisingly, innate immune pathway and neutrophil gene signature enrichment was associated with better outcomes. Thus, our work uncovers cellular molecular features of pathological organ ageing, identifiable at kidney retrieval, with translational potential.
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Affiliation(s)
- Roy Zhang
- Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK
| | - Patrick B Trotter
- Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK
| | - James McCaffrey
- Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK; Department of Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Rory Fitzroy
- Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK
| | - Giorgio Trivioli
- Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK
| | - Benjamin J Stewart
- Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK; Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK
| | - John R Ferdinand
- Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK
| | - Kevin W Loudon
- Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK
| | - Alexandra Riding
- Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK
| | - Jonathan West
- Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK
| | - Ashley Ferro
- Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK
| | - Menna R Clatworthy
- Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK; Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK.
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9
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Zhou AL, Rizaldi AA, Akbar AF, Ruck JM, King EA, Kilic A. Outcomes following concomitant multiorgan heart transplantation from circulatory death donors: The United States experience. J Heart Lung Transplant 2024; 43:1252-1262. [PMID: 38548240 DOI: 10.1016/j.healun.2024.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 02/03/2024] [Accepted: 03/16/2024] [Indexed: 04/11/2024] Open
Abstract
BACKGROUND Donation after circulatory death (DCD) has reemerged as a method of expanding the donor heart pool. Given the high waitlist mortality of multiorgan heart candidates, we evaluated waitlist outcomes associated with willingness to consider DCD offers and post-transplant outcomes following DCD transplant for these candidates. METHODS We identified adult multiorgan heart candidates and recipients between January 1, 2020 and March 31, 2023 nationally. Among candidates that met inclusion criteria, we compared the cumulative incidence of transplant, with waitlist death/deterioration as a competing risk, by willingness to consider DCD offers. Among recipients of DCD versus brain death (DBD) transplants, we compared perioperative outcomes and post-transplant survival. RESULTS Of 1,802 heart-kidney, 266 heart-liver, and 440 heart-lung candidates, 15.8%, 12.4%, and 31.1%, respectively, were willing to consider DCD offers. On adjusted analysis, willingness to consider DCD offers was associated with higher likelihood of transplant for all multiorgan heart candidates and decreased likelihood of waitlist deterioration for heart-lung candidates. Of 1,100 heart-kidney, 173 heart-liver, and 159 heart-lung recipients, 5.4%, 2.3%, and 2.5%, respectively, received DCD organs. Recipients of DCD and DBD heart-kidney transplants had a similar likelihood of perioperative outcomes and 1-year survival. All other DCD multiorgan heart recipients have survived to the last follow-up. CONCLUSIONS Multiorgan heart candidates who were willing to consider DCD offers had favorable waitlist outcomes, and heart-kidney recipients of DCD transplants had similar post-transplant outcomes to recipients of DBD transplants. We recommend the use of DCD organs to increase the donor pool for these high-risk candidates.
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Affiliation(s)
- Alice L Zhou
- Division of Cardiac Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland
| | - Alexandra A Rizaldi
- Division of Cardiac Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland
| | - Armaan F Akbar
- Division of Cardiac Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland
| | - Jessica M Ruck
- Division of Cardiac Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland
| | - Elizabeth A King
- Division of Transplant Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland
| | - Ahmet Kilic
- Division of Cardiac Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland.
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10
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Cheng XS, Lenihan CR. Expanding the Overton Window in Deceased Kidney Donor Eligibility-Enough to Make a Difference? JAMA 2024; 332:199-200. [PMID: 38780501 DOI: 10.1001/jama.2024.8734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/25/2024]
Affiliation(s)
- Xingxing S Cheng
- School of Medicine, Division of Nephrology, Stanford University, Stanford, California
| | - Colin R Lenihan
- School of Medicine, Division of Nephrology, Stanford University, Stanford, California
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11
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Avramidou E, Srinivasan D, Todorov D, Tsoulfas G, Papalois V. Diagnostic and Prognostic Value of Machine Perfusion Biomarkers in Kidney Graft Evaluation. Transplant Proc 2024; 56:1308-1318. [PMID: 39069459 DOI: 10.1016/j.transproceed.2024.05.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 05/24/2024] [Indexed: 07/30/2024]
Abstract
BACKGROUND With the rising prevalence of end-stage kidney disease, the use of expanded criteria donor allografts, seen as essential for meeting organ demand, still proves challenging due to their higher risk of graft loss, delayed function, and rejection. Machine perfusion, a technique in preserving allografts, offers improved allograft outcomes compared to static cold storage while allowing for the noninvasive measurement of kidney injury biomarkers in the perfusate solution. This offers an objective method to assess graft function at various preservation stages. MATERIALS AND METHODS We conducted a narrative review of the databases PubMed and Scopus, including studies written in the English language and published after 2010. RESULTS In this narrative review, we identified biomarkers, like 4-hydroxyproline, taurine, and glutathione transferase, as predictive markers of delayed graft function. Additionally, biomarkers, like extracellular histone h3, vascular cell adhesion protein, and matrix metalloprotease protein, have shown correlation with decreased graft function, although their predictive ability remains inconclusive. DISCUSSION The review outlines various suggestions for potential areas of research focus to enhance future expanded criteria donor allograft utilization. However, limitations exist, including the absence of a singular reliable biomarker and the challenges of validating biomarker effectiveness across diverse outcomes.
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Affiliation(s)
- Eleni Avramidou
- Department of Transplantation Surgery, Center for Research and Innovation in Solid Organ Transplantation, Aristotle University School of Medicine, Thessaloniki, Greece.
| | - Divya Srinivasan
- Department of Medicine, Imperial College London, London, United Kingdom
| | - Dominik Todorov
- Department of Medicine, Imperial College London, London, United Kingdom
| | - Georgios Tsoulfas
- Department of Transplantation Surgery, Center for Research and Innovation in Solid Organ Transplantation, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Vassilios Papalois
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
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12
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Rodriguez-Sanchez E, Aceves-Ripoll J, Mercado-García E, Navarro-García JA, Andrés A, Aguado JM, Segura J, Ruilope LM, Fernández-Ruiz M, Ruiz-Hurtado G. Donor-Dependent Variations in Systemic Oxidative Stress and Their Association with One-Year Graft Outcomes in Kidney Transplantation. Am J Nephrol 2024; 55:509-519. [PMID: 38857579 DOI: 10.1159/000539509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 05/20/2024] [Indexed: 06/12/2024]
Abstract
INTRODUCTION Oxidative stress has been implicated in complications after kidney transplantation (KT), including delayed graft function (DGF) and rejection. However, its role in long-term posttransplant outcomes remains unclear. METHODS We investigated oxidative damage and antioxidant defense dynamics, and their impact on the graft outcomes, in 41 KT recipients categorized by type of donation over 12 months. Oxidative status was determined using OxyScore and AntioxyScore indexes, which comprise several circulating biomarkers of oxidative damage and antioxidant defense. Donor types included donation after brain death (DBD [61.0%]), donation after circulatory death (DCD [26.8%]), and living donation (LD [12.1%]). RESULTS There was an overall increase in oxidative damage early after transplantation, which was significantly higher in DCD as compared to DBD and LD recipients. The multivariate adjustment confirmed the independent association of OxyScore and type of deceased donation with DGF, donor kidney function, and induction therapy with antithymocyte globulin. There were no differences in terms of antioxidant defense. Lower oxidative damage at day 7 predicted better graft function at 1-year posttransplant only in DBD recipients. CONCLUSION DCD induced greater short-term oxidative damage after KT, whereas the early levels of oxidative damage were predictive of the graft function 1 year after KT among DBD recipients.
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Affiliation(s)
- Elena Rodriguez-Sanchez
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
| | - Jennifer Aceves-Ripoll
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
| | - Elisa Mercado-García
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
| | - José A Navarro-García
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
| | - Amado Andrés
- Department of Nephrology, Hospital Universitario "12 de Octubre", Research Institute Hospital "12 de Octubre" (Imas12), Madrid, Spain
- School of Medicine, Universidad Complutense, Madrid, Spain
| | - José M Aguado
- School of Medicine, Universidad Complutense, Madrid, Spain
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Research Institute Hospital "12 de Octubre" (Imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Julián Segura
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
| | - Luis M Ruilope
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, Madrid, Spain
- European University of Madrid, Madrid, Spain
| | - Mario Fernández-Ruiz
- School of Medicine, Universidad Complutense, Madrid, Spain
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Research Institute Hospital "12 de Octubre" (Imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Gema Ruiz-Hurtado
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, Madrid, Spain
- Department of Physiology, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain
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13
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Yamani F, Cianfarini C, Batlle D. Delayed Graft Function and the Renin-angiotensin System. Transplantation 2024; 108:1308-1318. [PMID: 38361243 PMCID: PMC11136607 DOI: 10.1097/tp.0000000000004934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2024]
Abstract
Delayed graft function (DGF) is a form of acute kidney injury (AKI) and a common complication following kidney transplantation. It adversely influences patient outcomes increases the financial burden of transplantation, and currently, no specific treatments are available. In developing this form of AKI, activation of the renin-angiotensin system (RAS) has been proposed to play an important role. In this review, we discuss the role of RAS activation and its contribution to the pathophysiology of DGF following the different stages of the transplantation process, from procurement and ischemia to transplantation into the recipient and including data from experimental animal models. Deceased kidney donors, whether during cardiac or brain death, may experience activation of the RAS. That may be continued or further potentiated during procurement and organ preservation. Additional evidence suggests that during implantation of the kidney graft and reperfusion in the recipient, the RAS is activated and may likely remain activated, extrapolating from other forms of AKI where RAS overactivity is well documented. Of particular interest in this setting is the status of angiotensin-converting enzyme 2, a key RAS enzyme essential for the metabolism of angiotensin II and abundantly present in the apical border of the proximal tubules, which is the site of predominant injury in AKI and DGF. Interventions aimed at safely downregulating the RAS using suitable shorter forms of angiotensin-converting enzyme 2 could be a way to offer protection against DGF.
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Affiliation(s)
- Fatmah Yamani
- Division of Nephrology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - Cosimo Cianfarini
- Division of Nephrology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - Daniel Batlle
- Division of Nephrology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
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14
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Phillips B, Asgari E, Berry M, Callaghan C, Cerisuelo MC, Johnson P, Karydis N, Nasralla D, Nutu A, Oniscu G, Perera T, Sinha S, Sutherland A, Van Dellen D, Watson C, White S, O'Neill S. British Transplantation Society guidelines on abdominal organ transplantation from deceased donors after circulatory death. Transplant Rev (Orlando) 2024; 38:100801. [PMID: 37840003 DOI: 10.1016/j.trre.2023.100801] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 10/07/2023] [Indexed: 10/17/2023]
Abstract
The British Transplantation Society (BTS) 'Guideline on transplantation from deceased donors after circulatory death' has recently been updated and this manuscript summarises the relevant recommendations in abdominal organ transplantation from Donation after Circulatory Death (DCD) donors, encompassing the chapters on liver, kidney, pancreas and islet cell transplantation.
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Affiliation(s)
- Benedict Phillips
- Specialty Registrar in Transplant Surgery, Guy's Hospital, London, United Kingdom
| | - Ellie Asgari
- Consultant Nephrologist, Guy's Hospital, London, United Kingdom
| | - Miriam Berry
- Consultant Nephrologist, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - Chris Callaghan
- Consultant Transplant Surgeon, Guy's Hospital, London, United Kingdom
| | | | - Paul Johnson
- Consultant Paediatric Surgeon, John Radcliffe Hospital, Oxford, United Kingdom
| | - Nikolaos Karydis
- Consultant Transplant Surgeon, Guy's Hospital, London, United Kingdom
| | - David Nasralla
- Consultant Transplant Surgeon, Royal Free Hospital, London, United Kingdom
| | - Anisa Nutu
- Transplant Fellow, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - Gabi Oniscu
- Consultant Transplant Surgeon, Royal Infirmary, Edinburgh, United Kingdom
| | - Thamara Perera
- Consultant Transplant Surgeon, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - Sanjay Sinha
- Consultant Transplant Surgeon, Churchill Hospital, Oxford, United Kingdom
| | - Andrew Sutherland
- Consultant Transplant Surgeon, Royal Infirmary, Edinburgh, United Kingdom
| | - David Van Dellen
- Consultant Transplant Surgeon, Manchester Royal Infirmary, Manchester, United Kingdom
| | - Chris Watson
- Consultant Transplanxt Surgeon, Addenbrooke's Hospital, Cambridge, United Kingdom
| | - Steve White
- Consultant Transplant Surgeon, Freeman Hospital, Newcastle, United Kingdom
| | - Stephen O'Neill
- Consultant Transplant Surgeon, Belfast City Hospital, Belfast, United Kingdom.
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15
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Coello I, Martínez AI, Peraire M, Aizpiri L, Vega CA, Amer M, Guldris RJ, Bauzà Quetglas JL, Carmelo Pieras E. ¿Which peritransplant features can predict graft survival in donor after circulatory death kidney transplantation? Nefrologia 2023; 43:499-501. [PMID: 37813742 DOI: 10.1016/j.nefroe.2021.04.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 04/28/2021] [Indexed: 10/11/2023] Open
Affiliation(s)
- Iris Coello
- Servicio de Urología, Hospital Universitario Son Espases, Palma de Mallorca, Spain.
| | - Ana Isabel Martínez
- Servicio de Urología, Hospital Universitario Son Espases, Palma de Mallorca, Spain
| | - Maria Peraire
- Servicio de Urología, Hospital Universitario Son Espases, Palma de Mallorca, Spain
| | - Laura Aizpiri
- Servicio de Urología, Hospital Universitario Son Espases, Palma de Mallorca, Spain
| | - Camila Andrea Vega
- Servicio de Urología, Hospital Universitario Son Espases, Palma de Mallorca, Spain
| | - Miquel Amer
- Servicio de Urología, Hospital Universitario Son Espases, Palma de Mallorca, Spain
| | - Ricardo José Guldris
- Servicio de Urología, Hospital Universitario Son Espases, Palma de Mallorca, Spain
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16
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Sandal S, Cantarovich M, Cardinal H, Ramankumar AV, Senecal L, Collette S, Saw CL, Paraskevas S, Tchervenkov J. Predicting Long-term Outcomes in Deceased Donor Kidney Transplant Recipients Using Three Short-term Graft Characteristics. KIDNEY360 2023; 4:e809-e816. [PMID: 37211638 PMCID: PMC10371380 DOI: 10.34067/kid.0000000000000154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 03/28/2023] [Indexed: 05/23/2023]
Abstract
Key Points Delayed graft function is not an ideal measure of graft function, yet is used to assess risk in kidney transplantation. We propose a model that combines it with two other measures of 90-day graft function to identify recipients at incremental risk of inferior long-term outcomes. Background Delayed graft function (DGF) in kidney transplant recipients is used to determine graft prognosis, make organ utilization decisions, and as an important end point in clinical trials. However, DGF is not an ideal measure of graft function. We aimed to develop and validate a model that provides incremental risk assessment for inferior patient and graft outcomes. Methods We included adult kidney-only deceased donor transplant recipients from 1996 to 2016. In addition to DGF, two short-term measures were used to assess risk: renal function recovery <100% (attaining half the donor's eGFR) and recipient's 90-day eGFR <30. Recipients were at no, low, moderate, or high risk if they met zero, one, two, or all criteria, respectively. Cox proportional hazard models were used to assess the independent relationship between exposure and death-censored graft failure (DCGF) and mortality. Results Of the 792 eligible recipients, 24.5% experienced DGF, 40.5% had renal function recovery <100%, and 6.9% had eGFR <30. Over a median follow-up of 7.3 years, the rate of DCGF was 18.7% and mortality was 25.1%. When compared with recipients at no risk, those at low, moderate, and high risk were noted to have an increase in risk of DCGF (adjusted hazard ratio [aHR], 1.53; 95% confidence interval [CI], 1.03 to 2.27; aHR, 2.84; 95% CI, 1.68 to 4.79; aHR, 15.46; 95% CI, 8.04 to 29.71) and mortality (aHR, 1.16; 95% CI, 0.84 to 1.58; aHR, 1.85; 95% CI, 1.13 to 3.07; aHR, 2.66; 95% CI, 1.19 to 5.97). When using a hierarchical approach, each additional exposure predicted the risk of DCGF better than DGF alone and 100 random bootstrap replications supported the internal validity of the risk model. In an external validation cohort deemed to be at lower risk of DCGF, similar nonsignificant trends were noted. Conclusion We propose a risk model that provides an incremental assessment of recipients at higher risk of adverse long-term outcomes than DGF alone. This can help advance the field of risk assessment in transplantation and inform therapeutic decision making in patients at the highest spectrum of inferior outcomes.
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Affiliation(s)
- Shaifali Sandal
- Division of Nephrology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
- Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
- Multiorgan Transplant Program, Departments of Medicine and Surgery, McGill University Health Centre, Montreal, Quebec, Canada
- Division of Experimental Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Marcelo Cantarovich
- Division of Nephrology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
- Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
- Multiorgan Transplant Program, Departments of Medicine and Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Heloise Cardinal
- Department of Medicine, University of Montreal, Montreal, Quebec, Canada
| | | | - Lynne Senecal
- Department of Medicine, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
| | - Suzon Collette
- Department of Medicine, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
| | - Chee Long Saw
- Multiorgan Transplant Program, Departments of Medicine and Surgery, McGill University Health Centre, Montreal, Quebec, Canada
- Division of Hematology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Steven Paraskevas
- Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
- Multiorgan Transplant Program, Departments of Medicine and Surgery, McGill University Health Centre, Montreal, Quebec, Canada
- Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Jean Tchervenkov
- Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
- Multiorgan Transplant Program, Departments of Medicine and Surgery, McGill University Health Centre, Montreal, Quebec, Canada
- Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada
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17
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Abstract
PURPOSE OF REVIEW Optimizing deceased donor organ utilization is gaining recognition as a topical and important issue, both in the United Kingdom (UK) and globally. This review discusses pertinent issues in the field of organ utilization, with specific reference to UK data and recent developments within the UK. RECENT FINDINGS A multifaceted approach is likely required in order to improve organ utilization. Having a solid evidence-base upon which transplant clinicians and patients on national waiting lists can base decisions regarding organ utilization is imperative in order to bridge gaps in knowledge regarding the optimal use of each donated organ. A better understanding of the risks and benefits of the uses of higher risk organs, along with innovations such as novel machine perfusion technologies, can help clinician decision-making and may ultimately reduce the unnecessary discard of precious deceased donor organs. SUMMARY The issues facing the UK with regards to organ utilization are likely to be similar to those in many other developed countries. Discussions around these issues within organ donation and transplantation communities may help facilitate shared learning, lead to improvements in the usage of scarce deceased donor organs, and enable better outcomes for patients waiting for transplants.
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Affiliation(s)
- Maria Ibrahim
- Department of Nephrology and Transplantation, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester
| | - Chris J Callaghan
- Department of Nephrology and Transplantation, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London
- NHS Blood and Transplant, Bristol, UK
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18
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Shi B, Ying T, Xu J, Wyburn K, Laurence J, Chadban SJ. Obesity is Associated With Delayed Graft Function in Kidney Transplant Recipients: A Paired Kidney Analysis. Transpl Int 2023; 36:11107. [PMID: 37324221 PMCID: PMC10261700 DOI: 10.3389/ti.2023.11107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 05/11/2023] [Indexed: 06/17/2023]
Abstract
Obesity is increasingly prevalent among candidates for kidney transplantation. Existing studies have shown conflicting post-transplant outcomes for obese patients which may relate to confounding bias from donor-related characteristics that were unaccounted for. We used ANZDATA Registry data to compare graft and patient survival between obese (BMI >27.5 kg/m2 Asians; >30 kg/m2 non-Asians) and non-obese kidney transplant recipients, while controlling for donor characteristics by comparing recipients of paired kidneys. We selected transplant pairs (2000-2020) where a deceased donor supplied one kidney to an obese candidate and the other to a non-obese candidate. We compared the incidence of delayed graft function (DGF), graft failure and death by multivariable models. We identified 1,522 pairs. Obesity was associated with an increased risk of DGF (aRR = 1.26, 95% CI 1.11-1.44, p < 0.001). Obese recipients were more likely to experience death-censored graft failure (aHR = 1.25, 95% CI 1.05-1.49, p = 0.012), and more likely to die with function (aHR = 1.32, 95% CI 1.15-1.56, p = 0.001), versus non-obese recipients. Long-term patient survival was significantly worse in obese patients with 10- and 15-year survival of 71% and 56% compared to 77% and 63% in non-obese patients. Addressing obesity is an unmet clinical need in kidney transplantation.
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Affiliation(s)
- Bree Shi
- Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia
- Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, South Australia Health and Medicine Research Institute, Adelaide, SA, Australia
| | - Tracey Ying
- Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia
- Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, South Australia Health and Medicine Research Institute, Adelaide, SA, Australia
- Renal Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Josephine Xu
- Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, South Australia Health and Medicine Research Institute, Adelaide, SA, Australia
- Department of Transplant Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
- Institute of Academic Surgery, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Kate Wyburn
- Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, South Australia Health and Medicine Research Institute, Adelaide, SA, Australia
- Renal Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
- School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Jerome Laurence
- Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, South Australia Health and Medicine Research Institute, Adelaide, SA, Australia
- Department of Transplant Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
- Institute of Academic Surgery, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Steven J Chadban
- Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia
- Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, South Australia Health and Medicine Research Institute, Adelaide, SA, Australia
- Renal Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
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19
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Fan LW, Li YR, Lin KJ, Pan PY, Liu KL, Lin CT, Chiang YJ, Chu SH, Wang HH. The Impact of Intraoperative Graft Blood Flow Measurement on Early Graft Function. Transplant Proc 2023:S0041-1345(23)00308-1. [PMID: 37246131 DOI: 10.1016/j.transproceed.2023.04.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/15/2023] [Accepted: 04/19/2023] [Indexed: 05/30/2023]
Abstract
BACKGROUND The aim of this study is to evaluate the impact of intraoperative allograft vascular flow on early kidney graft function. METHODS A total of 159 patients underwent kidney transplantation from January 2017 to March 2022 at Linkou Chang Gung Memorial Hospital. Graft arterial and venous blood flow was measured separately with a transient time flowmeter (Transonic HT353; Transonic Systems, Inc, Ithaca, NY, United States) after ureteroneocystostomy. The early outcomes, including the postoperative creatinine level, were analyzed accordingly. RESULTS There were 83 males and 76 females, with a mean age of 44.5 years. The mean graft arterial flow measured was 480.6 mL/min, and the mean venous flow was 506.2 mL/min. Delayed graft function (DGF) incidence was 36.5%, 32.5%, and 40.8% in total, living, and deceased donor groups, respectively. Living donor and deceased donor kidney transplantation were analyzed separately. In the DGF subgroup, there were lower graft venous flows, higher body mass index (BMI), and more male patients in the living kidney transplant group. Similarly, the deceased donor kidney transplantation group with delayed graft function tended to have higher body height, higher body weight, higher BMI, and more diabetes mellitus. The multivariate analysis showed that lower graft venous blood flow (odds ratio [OR] = 0.995, P = .008) and higher BMI (OR = 1.144, P = .042) were significantly correlated with delayed graft function in living donor kidney transplantations. In the deceased donor group, a multivariate analysis of risk factors showed that BMI had a significant correlation with delayed graft function (OR = 1.41, P = .039). CONCLUSIONS Graft venous blood flow was significantly associated with delayed graft function in living donor kidney transplantation, and high BMI was correlated with DGF in all patients receiving kidney transplantation.
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Affiliation(s)
- Le-Wei Fan
- Department of Urology, New Taipei Municipal Tu Cheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei City, Taiwan
| | - Yun-Ren Li
- Department of Urology, New Taipei Municipal Tu Cheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei City, Taiwan; Department of Urology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan
| | - Kuo-Jen Lin
- Department of Urology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang-Gung University, Taoyuan, Taiwan; Chang-Gung Transplant Institute, Taoyuan, Taiwan
| | - Pai-Yen Pan
- Department of Urology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan
| | - Kuan-Lin Liu
- Department of Urology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang-Gung University, Taoyuan, Taiwan; Chang-Gung Transplant Institute, Taoyuan, Taiwan
| | - Chih-Te Lin
- Department of Urology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang-Gung University, Taoyuan, Taiwan
| | - Yang-Jen Chiang
- Department of Urology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang-Gung University, Taoyuan, Taiwan; Chang-Gung Transplant Institute, Taoyuan, Taiwan
| | - Sheng-Hsien Chu
- Department of Urology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang-Gung University, Taoyuan, Taiwan; Chang-Gung Transplant Institute, Taoyuan, Taiwan
| | - Hsu-Han Wang
- Department of Urology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang-Gung University, Taoyuan, Taiwan; Chang-Gung Transplant Institute, Taoyuan, Taiwan.
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20
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Meertens P, Mellati A, Dumbill R, Lo Faro ML, Rozenberg K, Mulvey J, Fliri H, Ploeg R, Hunter J. CC-4066 therapy delivered to kidneys during cold storage and assessed with normothermic reperfusion is feasible and safe. FRONTIERS IN TRANSPLANTATION 2023; 2:1166661. [PMID: 39055309 PMCID: PMC11270626 DOI: 10.3389/frtra.2023.1166661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 04/21/2023] [Indexed: 07/27/2024]
Abstract
Introduction Currently there is an urgent need to translate interventions that may be beneficial to marginal donor kidneys prior to transplant, to improve their quality from bench to bedside. This project investigated the effects of CC-4066, a potent dual inhibitor of cyclophilin proteins A and D, treatment during static cold storage (SCS) in a porcine model of renal ischemia-reperfusion injury (IRI) using Normothermic Reperfusion (NR). Materials and methods Porcine kidneys and autologous blood were retrieved in pairs from a local abattoir (n = 7). One kidney from each pair was randomly allocated to treatment and one allocated to control and flushed with preservation solution containing CC-4066 or vehicle. After 7 h of SCS kidneys underwent 3 h Normothermic Reperfusion (NR) with autologous whole blood while perfusion characteristics and samples were collected. Results Perfusion and metabolic parameters showed similar trends and no statistical differences were observed between the groups. IL-6 showed a significant increase over time but no significant difference between groups (p-value 0.009 and 0.14 respectively, two-way ANOVA). Oxygen consumption and lactate levels were similar between groups but there was increased vacuolation on histology in the control group. Conclusions The addition of CC-4066 during SCS of kidneys is safe and feasible and has no adverse or detrimental effects on perfusion during assessment on NR. There was no difference in cytokine levels although there was a trend towards less vacuolation on histology in the treatment group.
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Affiliation(s)
- Pommelien Meertens
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdoms
- Leiden University Medical Centre, Leiden University, Leiden, Netherlands
| | - Azita Mellati
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdoms
| | - Richard Dumbill
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdoms
- Oxford University Hospital National Health Service (NHS) Foundation Trust, Oxford, United Kingdom
| | - M. Letizia Lo Faro
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdoms
| | - Kaithlyn Rozenberg
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdoms
| | - John Mulvey
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdoms
| | - Hans Fliri
- Cypralis Ltd., Cambridge, United Kingdom
| | - Rutger Ploeg
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdoms
- Leiden University Medical Centre, Leiden University, Leiden, Netherlands
- Oxford University Hospital National Health Service (NHS) Foundation Trust, Oxford, United Kingdom
| | - James Hunter
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdoms
- University Hospitals of Coventry and Warwickshire National Health Service (NHS) Trust, Coventry, United Kingdom
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21
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Rao JS, Pruett TL. Immunology of the transplanted cryopreserved kidney. Cryobiology 2023; 110:1-7. [PMID: 36640932 DOI: 10.1016/j.cryobiol.2023.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/28/2022] [Accepted: 01/10/2023] [Indexed: 01/13/2023]
Abstract
Transplantation has substituted dysfunctional organs with healthy organs from donors to significantly lower morbidity and mortality associated with end-stage organ disease. Since the advent of transplantation, the promise of functional replacement has attracted an exponential mismatch between organ supply and demand. Theoretical proposals to counter the increasing needs have either been to create a source through genetic engineering of porcine donors for xenotransplantation (with more potent immunosuppression protocols) or recreate one's organ in a pig using interspecies blastocyst complementation for exogenic organ transplantation (without immunosuppression). Another promising avenue has been organ banking through cryopreservation for transplantation. Although ice free preservation and acceptable early function following rewarming is critical for success in transplantation, the immunological response that predominantly defines short- and long-term graft survival has failed to captivate attention to date. It is well sorted that thermal and metabolic stress incurred at 4 °C during recovery and reperfusion of organs for clinical transplantation has varying impact on graft survival. Considering the magnitude of cellular imbalance and injury at sub-zero/ultralow temperatures in addition to the chemical toxicity of cryoprotective agents (CPA), it is essential to assess and address the immunological response associated following transplantation to maximize the success of cryopreservation.
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Affiliation(s)
- Joseph Sushil Rao
- Division of Solid Organ Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN, USA; Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
| | - Timothy L Pruett
- Division of Solid Organ Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
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22
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Sousa Da Silva RX, Darius T, Mancina L, Eden J, Wernlé K, Ghoneima AS, Barlow AD, Clavien PA, Dutkowski P, Kron P. Real-time assessment of kidney allografts during HOPE using flavin mononucleotide (FMN) - a preclinical study. FRONTIERS IN TRANSPLANTATION 2023; 2:1132673. [PMID: 38993877 PMCID: PMC11235286 DOI: 10.3389/frtra.2023.1132673] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 02/06/2023] [Indexed: 07/13/2024]
Abstract
INTRODUCTION The gap between available donor grafts and patients on the waiting lists is constantly growing. This leads to an increased utilization of high-risk and therefore more vulnerable kidney grafts. The use of high-risk organs requires further optimization of machine preservation and assessment strategies before transplantation. Hypothermic machine perfusion (HMP) is the standard of care for kidneys originating from donation after circulatory death (DCD), whereas the evidence of HMP with additional oxygen (HOPE) is still very limited. Furthermore, an objective quality assessment of HMP-perfused kidneys is lacking. Recently, the release of mitochondria derived fragments, i.e., flavin mononucleotide (FMN) of complex I during machine liver perfusion was shown to be predictive for liver graft function before implantation. Therefore, the aim of this study was to evaluate, if FMN is useful also for assessment of kidney injury before use. METHODS A porcine perfusion model was used to investigate the feasibility of assessment of kidney grafts during hypothermic oxygenated perfusion (HOPE) with either 0, 30 or 60 minutes of warm ischemia. The model with warm ischemia times (WIT) of 30 min and 60 min, was used to mimic a clinically relevant scenario. A group with no warm ischemia time (0' WIT) served as control group. The groups underwent minimal static cold storage (SCS) of 2 h followed by 2 h of end-ischemic HOPE with repeated real-time FMN measurements. In a further step, these values were related to the release of damage-associated molecular patterns (DAMPs) and to the functionality of the respiratory chain, represented by the capacity of ATP production. RESULTS We demonstrate, first, feasibility of perfusate FMN measurements in perfused kidneys, and secondly its correlation with donor warm ischemia time. Accordingly, FMN measurement showed significantly higher release in the 60-minute WIT group (n = 4) compared to the 30-minute WIT (n = 4) and the control group (n = 4). FMN release correlated also with DAMP signaling, such as the release of 8-OHdG and HMGB1. Finally, ATP replenishment proved to be best in control kidneys, followed by kidneys with 30 min and then by kidneys with 60 min of WIT. DISCUSSION This study demonstrates the feasibility of FMN measurement in kidneys during HOPE. In addition, we show a correlation between FMN quantification and pre-existing kidney graft injury. Based on this, real-time FMN measurement during HOPE may be an objective assessment tool to accept high-risk kidneys for transplantation while minimizing post-transplant dysfunction, moving away from former "gut feeling" towards objective criteria in accepting marginal kidney grafts for transplantation. Graft evaluation based on these results may close the gap between available grafts and patients on the waiting lists by increasing utilization rates without significant impact for the recipients.
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Affiliation(s)
- Richard X. Sousa Da Silva
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Tom Darius
- Department of Surgery, Surgery and Abdominal Transplant Unit, University Clinics Saint Luc, Université catholique de Louvain, Brussels, Belgium
- Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Chirurgie Expérimentale et Transplantation, Université catholique de Louvain, Brussels, Belgium
| | - Leandro Mancina
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Janina Eden
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Kendra Wernlé
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Ahmed S. Ghoneima
- Department of HPB and Transplant Surgery, St. James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Adam D. Barlow
- Department of HPB and Transplant Surgery, St. James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Pierre-Alain Clavien
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Philipp Dutkowski
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Philipp Kron
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
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23
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Akalay S, Hosgood SA. How to Best Protect Kidneys for Transplantation-Mechanistic Target. J Clin Med 2023; 12:jcm12051787. [PMID: 36902572 PMCID: PMC10003664 DOI: 10.3390/jcm12051787] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 02/15/2023] [Accepted: 02/17/2023] [Indexed: 02/25/2023] Open
Abstract
The increasing number of patients on the kidney transplant waiting list underlines the need to expand the donor pool and improve kidney graft utilization. By protecting kidney grafts adequately from the initial ischemic and subsequent reperfusion injury occurring during transplantation, both the number and quality of kidney grafts could be improved. The last few years have seen the emergence of many new technologies to abrogate ischemia-reperfusion (I/R) injury, including dynamic organ preservation through machine perfusion and organ reconditioning therapies. Although machine perfusion is gradually making the transition to clinical practice, reconditioning therapies have not yet progressed from the experimental setting, pointing towards a translational gap. In this review, we discuss the current knowledge on the biological processes implicated in I/R injury and explore the strategies and interventions that are being proposed to either prevent I/R injury, treat its deleterious consequences, or support the reparative response of the kidney. Prospects to improve the clinical translation of these therapies are discussed with a particular focus on the need to address multiple aspects of I/R injury to achieve robust and long-lasting protective effects on the kidney graft.
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Affiliation(s)
- Sara Akalay
- Department of Development and Regeneration, Laboratory of Pediatric Nephrology, KU Leuven, 3000 Leuven, Belgium
| | - Sarah A. Hosgood
- Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UK
- Correspondence:
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24
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Ducousso H, Vallée M, Kerforne T, Castilla I, Duthe F, Saulnier PJ, Ragot S, Thierry A. Paving the Way for Personalized Medicine in First Kidney Transplantation: Interest of a Creatininemia Latent Class Analysis in Early Post-transplantation. Transpl Int 2023; 36:10685. [PMID: 36873744 PMCID: PMC9977818 DOI: 10.3389/ti.2023.10685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 01/10/2023] [Indexed: 02/18/2023]
Abstract
Plasma creatinine is a marker of interest in renal transplantation but data on its kinetics in the first days following transplantation are scarce. The aim of this study was to identify clinically relevant subgroups of creatinine trajectories following renal transplantation and to test their association with graft outcome. Among 496 patients with a first kidney transplant included in the French ASTRE cohort at the Poitiers University hospital, 435 patients from donation after brain death were considered in a latent class modeling. Four distinct classes of creatinine trajectories were identified: "poor recovery" (6% of patients), "intermediate recovery" (47%), "good recovery" (10%) and "optimal recovery" (37%). Cold ischemia time was significantly lower in the "optimal recovery" class. Delayed graft function was more frequent and the number of hemodialysis sessions was higher in the "poor recovery" class. Incidence of graft loss was significantly lower in "optimal recovery" patients with an adjusted risk of graft loss 2.42 and 4.06 times higher in "intermediate recovery" and "poor recovery" patients, respectively. Our study highlights substantial heterogeneity in creatinine trajectories following renal transplantation that may help to identify patients who are more likely to experience a graft loss.
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Affiliation(s)
- Héloïse Ducousso
- Department of Urology, University of Poitiers, CHU Poitiers, Poitiers, France
| | - Maxime Vallée
- Department of Urology, University of Poitiers, CHU Poitiers, Poitiers, France
| | - Thomas Kerforne
- Department of Intensive Care, University of Poitiers, CHU Poitiers, Poitiers, France
| | - Ines Castilla
- Clinical Investigation Centre CIC1402, Poitiers University, Institut National de la santé et de la recherche médicale (INSERM), CHU Poitiers, Poitiers, France
| | - Fabien Duthe
- Department of Urology, University of Poitiers, CHU Poitiers, Poitiers, France
| | - Pierre-Jean Saulnier
- Clinical Investigation Centre CIC1402, Poitiers University, Institut National de la santé et de la recherche médicale (INSERM), CHU Poitiers, Poitiers, France
| | - Stéphanie Ragot
- Clinical Investigation Centre CIC1402, Poitiers University, Institut National de la santé et de la recherche médicale (INSERM), CHU Poitiers, Poitiers, France
| | - Antoine Thierry
- Department of Nephrology, Dialysis and Transplantation, University of Poitiers, CHU Poitiers, Poitiers, France
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25
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de Rougemont O, Deng Y, Frischknecht L, Wehmeier C, Villard J, Ferrari-Lacraz S, Golshayan D, Gannagé M, Binet I, Wirthmueller U, Sidler D, Schachtner T, Schaub S, Nilsson J. Donation type and the effect of pre-transplant donor specific antibodies - Data from the Swiss Transplant Cohort Study. Front Immunol 2023; 14:1104371. [PMID: 36875145 PMCID: PMC9974644 DOI: 10.3389/fimmu.2023.1104371] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 01/30/2023] [Indexed: 02/19/2023] Open
Abstract
Introduction The type of donation may affect how susceptible a donor kidney is to injury from pre-existing alloimmunity. Many centers are, therefore, reluctant to perform donor specific antibody (DSA) positive transplantations in the setting of donation after circulatory death (DCD). There are, however, no large studies comparing the impact of pre-transplant DSA stratified on donation type in a cohort with a complete virtual cross-match and long-term follow-up of transplant outcome. Methods We investigated the effect of pre-transplant DSA on the risk of rejection, graft loss, and the rate of eGFR decline in 1282 donation after brain death (DBD) transplants and compared it to 130 (DCD) and 803 living donor (LD) transplants. Results There was a significant worse outcome associated with pre-transplant DSA in all of the studied donation types. DSA directed against Class II HLA antigens as well as a high cumulative mean fluorescent intensity (MFI) of the detected DSA showed the strongest association with worse transplant outcome. We could not detect a significant additive negative effect of DSA in DCD transplantations in our cohort. Conversely, DSA positive DCD transplants appeared to have a slightly better outcome, possibly in part due to the lower mean fluorescent intensity (MFI) of the pre-transplant DSA. Indeed when DCD transplants were compared to DBD transplants with similar MFI (<6.5k), graft survival was not significantly different. Discussion Our results suggest that the negative impact of pre-transplant DSA on graft outcome could be similar between all donation types. This suggests that immunological risk assessment could be performed in a similar way regardless of the type of donor kidney transplantation.
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Affiliation(s)
- Olivier de Rougemont
- Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Yun Deng
- Department of Immunology, University Hospital Zurich (USZ), Zurich, Switzerland
| | - Lukas Frischknecht
- Department of Immunology, University Hospital Zurich (USZ), Zurich, Switzerland
| | - Caroline Wehmeier
- Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
| | - Jean Villard
- Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland
| | - Sylvie Ferrari-Lacraz
- Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland
| | - Déla Golshayan
- Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland
| | - Monique Gannagé
- Service of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Isabelle Binet
- Nephrology & Transplantation Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Urs Wirthmueller
- Department of Laboratory Medicine, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Daniel Sidler
- Department of Nephrology and Hypertension, Inselspital, Berne University Hospital and University of Berne, Berne, Switzerland
| | - Thomas Schachtner
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Stefan Schaub
- Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
| | - Jakob Nilsson
- Department of Immunology, University Hospital Zurich (USZ), Zurich, Switzerland
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26
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Oniscu GC, Mehew J, Butler AJ, Sutherland A, Gaurav R, Hogg R, Currie I, Jones M, Watson CJE. Improved Organ Utilization and Better Transplant Outcomes With In Situ Normothermic Regional Perfusion in Controlled Donation After Circulatory Death. Transplantation 2023; 107:438-448. [PMID: 35993664 DOI: 10.1097/tp.0000000000004280] [Citation(s) in RCA: 88] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND . We evaluated whether the use of normothermic regional perfusion (NRP) was associated with increased organ recovery and improved transplant outcomes from controlled donation after circulatory death (cDCD). METHODS . This is a retrospective analysis of UK adult cDCD donors' where at least 1 abdominal organ was accepted for transplantation between January 1, 2011, and December 31, 2019. RESULTS . A mean of 3.3 organs was transplanted when NRP was used compared with 2.6 organs per donor when NRP was not used. When adjusting for organ-specific donor risk profiles, the use of NRP increased the odds of all abdominal organs being transplanted by 3-fold for liver ( P < 0.0001; 95% confidence interval [CI], 2.20-4.29), 1.5-fold for kidney ( P = 0.12; 95% CI, 0.87-2.58), and 1.6-fold for pancreas ( P = 0.0611; 95% CI, 0.98-2.64). Twelve-mo liver transplant survival was superior for recipients of a cDCD NRP graft with a 51% lower risk-adjusted hazard of transplant failure (HR = 0.494). In risk-adjusted analyses, NRP kidneys had a 35% lower chance of developing delayed graft function than non-NRP kidneys (odds ratio, 0.65; 95% CI, 0.465-0.901)' and the expected 12-mo estimated glomerular filtration rate was 6.3 mL/min/1.73 m 2 better if abdominal NRP was used ( P < 0.0001). CONCLUSIONS . The use of NRP during DCD organ recovery leads to increased organ utilization and improved transplant outcomes compared with conventional organ recovery.
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Affiliation(s)
- Gabriel C Oniscu
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Little France Crescent, Edinburgh, United Kingdom
- Department of Clinical Surgery, University of Edinburgh, Edinburgh, United Kingdom
| | - Jennifer Mehew
- Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, United Kingdom
| | - Andrew J Butler
- University of Cambridge Department of Surgery, Addenbrooke's Hospital, Cambridge, the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre and the NIHR Blood and Transplant Research Unit (BTRU) at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), London, United Kingdom
- Cambridge Transplant Unit, Cambridge University Hospitals NHS Trust, Addenbrooke's Hospital, Bristol, United Kingdom
| | - Andrew Sutherland
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Little France Crescent, Edinburgh, United Kingdom
- Department of Clinical Surgery, University of Edinburgh, Edinburgh, United Kingdom
| | - Rohit Gaurav
- Cambridge Transplant Unit, Cambridge University Hospitals NHS Trust, Addenbrooke's Hospital, Bristol, United Kingdom
| | - Rachel Hogg
- Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, United Kingdom
| | - Ian Currie
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Little France Crescent, Edinburgh, United Kingdom
- Department of Clinical Surgery, University of Edinburgh, Edinburgh, United Kingdom
| | - Mark Jones
- Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, United Kingdom
| | - Christopher J E Watson
- University of Cambridge Department of Surgery, Addenbrooke's Hospital, Cambridge, the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre and the NIHR Blood and Transplant Research Unit (BTRU) at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), London, United Kingdom
- Cambridge Transplant Unit, Cambridge University Hospitals NHS Trust, Addenbrooke's Hospital, Bristol, United Kingdom
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27
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van Smaalen TC, Beurskens DMH, Kox JJHFM, Polonia R, Vos R, Duimel H, van de Wetering WJ, López-Iglesias C, Reutelingsperger CP, Ernest van Heurn LW, Peutz-Kootstra CJ, Nicolaes GAF. Extracellular histone release by renal cells after warm and cold ischemic kidney injury: Studies in an ex-vivo porcine kidney perfusion model. PLoS One 2023; 18:e0279944. [PMID: 36662718 PMCID: PMC9858092 DOI: 10.1371/journal.pone.0279944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 12/17/2022] [Indexed: 01/21/2023] Open
Abstract
Extracellular histones are cytotoxic molecules involved in experimental acute kidney injury. In patients receiving a renal transplant from donors after circulatory death, who suffer from additional warm ischemia, worse graft outcome is associated with higher machine perfusate extracellular histone H3 concentrations. We now investigated temperature-dependent extracellular histone release in an ex vivo porcine renal perfusion model, and subsequently studied histone release in the absence and presence of non-anticoagulant heparin. Seven pairs of ischemically damaged porcine kidneys were machine perfused at 4°C (cold ischemia) or 28°C (warm ischemia). Perfusate histone H3 concentration was higher after warm as compared to cold ischemia (median (IQR) = 0.48 (0.20-0.83) μg/mL vs. 0.02 (0.00-0.06) μg/mL; p = .045, respectively). Employing immune-electron microscopy (EM), histone containing cytoplasmic protrusions of tubular and endothelial cells were found after warm ischemic injury. Furthermore, abundant histone localization was detected in debris surrounding severely damaged glomerular cells, in a "buck shot" pattern. In vitro, histones were cytotoxic to endothelial and kidney epithelial cells in a temperature-dependent manner. In a separate ex vivo experiment, addition of heparin did not change the total histone H3 levels observed in the perfusate but revealed a continuous increase in the level of a lower molecular weight histone H3 variant. Our findings show that ischemically damaged kidneys release more extracellular histones in warm ischemia, which by EM was due to histone release by renal cells. Blocking of histone-mediated damage during transplantation may be beneficial in prevention of renal injury.
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Affiliation(s)
- Tim C. van Smaalen
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Danielle M. H. Beurskens
- Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
| | - Jasper J. H. F. M. Kox
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Rasheendra Polonia
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Rein Vos
- Department of Methodology and Statistics, School for Public Health and Primary Care (CAPHRI), Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
| | - Hans Duimel
- Microscopy CORE Lab, Maastricht Multimodal Molecular Imaging Institute, FHML, Maastricht University, Maastricht, The Netherlands
| | - Willine J. van de Wetering
- Microscopy CORE Lab, Maastricht Multimodal Molecular Imaging Institute, FHML, Maastricht University, Maastricht, The Netherlands
| | - Carmen López-Iglesias
- Microscopy CORE Lab, Maastricht Multimodal Molecular Imaging Institute, FHML, Maastricht University, Maastricht, The Netherlands
| | - Chris P. Reutelingsperger
- Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
| | - L. W. Ernest van Heurn
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Carine J. Peutz-Kootstra
- Department of Pathology, Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands
| | - Gerry A. F. Nicolaes
- Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
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28
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Use of Kidneys from Anencephalic Donors to Offset Organ Shortage. URO 2023. [DOI: 10.3390/uro3010002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Background: It is well recognized that patient survival and quality of life are superior with renal transplantation than with dialysis. Organ availability is far outweighed by the large number of wait-listed patients. Additional stratagems are sought to expand the donor pool, and kidneys from anencephalic infants can be considered a source of organs, until now unexplored. We plan to assess the feasibility of using the kidneys from anencephalic infants for transplantation. Material and Methods: Information about anencephaly, the characteristics of the infant kidneys, the ethical, social and medico-legal aspects raised by the use of these kidneys, their procurement and their transplantation are reviewed. Conclusions: En bloc kidney transplants from infants can provide long-term normal renal function after an accelerated catch up growth. They are not subjected to hyperfiltration since they have a full complement of nephrons. They can be transplanted using the techniques currently available.
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29
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Lehmann C, Pehnke S, Weimann A, Bachmann A, Dittrich K, Petzold F, Fürst D, de Fallois J, Landgraf R, Henschler R, Lindner TH, Halbritter J, Doxiadis I, Popp B, Münch J. Extended genomic HLA typing identifies previously unrecognized mismatches in living kidney transplantation. Front Immunol 2023; 14:1094862. [PMID: 36776892 PMCID: PMC9911689 DOI: 10.3389/fimmu.2023.1094862] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 01/12/2023] [Indexed: 01/28/2023] Open
Abstract
Introduction Antibody mediated rejection (ABMR) is the most common cause of long-term allograft loss in kidney transplantation (KT). Therefore, a low human leukocyte antigen (HLA) mismatch (MM) load is favorable for KT outcomes. Hitherto, serological or low-resolution molecular HLA typing have been adapted in parallel. Here, we aimed to identify previously missed HLA mismatches and corresponding antibodies by high resolution HLA genotyping in a living-donor KT cohort. Methods 103 donor/recipient pairs transplanted at the University of Leipzig Medical Center between 1998 and 2018 were re-typed using next generation sequencing (NGS) of the HLA loci -A, -B, -C, -DRB1, -DRB345, -DQA1, -DQB1, -DPA1, and -DPB1. Based on these data, we compiled HLA MM counts for each pair and comparatively evaluated genomic HLA-typing with pre-transplant obtained serological/low-resolution HLA (=one-field) typing results. NGS HLA typing (=two-field) data was further used for reclassification of de novo HLA antibodies as "donor-specific". Results By two-field HLA re-typing, we were able to identify additional MM in 64.1% (n=66) of cases for HLA loci -A, -B, -C, -DRB1 and -DQB1 that were not observed by one-field HLA typing. In patients with biopsy proven ABMR, two-field calculated MM count was significantly higher than by one-field HLA typing. For additional typed HLA loci -DRB345, -DQA1, -DPA1, and -DPB1 we observed 2, 26, 3, and 23 MM, respectively. In total, 37.3% (69/185) of de novo donor specific antibodies (DSA) formation was directed against these loci (DRB345 ➔ n=33, DQA1 ➔ n=33, DPA1 ➔ n=1, DPB1 ➔ n=10). Conclusion Our results indicate that two-field HLA typing is feasible and provides significantly more sensitive HLA MM recognition in living-donor KT. Furthermore, accurate HLA typing plays an important role in graft management as it can improve discrimination between donor and non-donor HLA directed cellular and humoral alloreactivity in the long range. The inclusion of additional HLA loci against which antibodies can be readily detected, HLA-DRB345, -DQA1, -DQB1, -DPA1, and -DPB1, will allow a more precise virtual crossmatch and better prediction of potential DSA. Furthermore, in living KT, two-field HLA typing could contribute to the selection of the immunologically most suitable donors.
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Affiliation(s)
- Claudia Lehmann
- Institute for Transfusion Medicine, University Hospital Leipzig, Leipzig, Germany
| | - Sarah Pehnke
- Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany
| | - Antje Weimann
- Division of Visceral Surgery and Transplantation Medicine, University of Leipzig Medical Center, Leipzig, Germany
| | - Anette Bachmann
- Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany
| | - Katalin Dittrich
- Department of Pediatric Nephrology, University of Leipzig Medical Center, Leipzig, Germany
| | - Friederike Petzold
- Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany
| | - Daniel Fürst
- Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Jonathan de Fallois
- Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany
| | - Ramona Landgraf
- Institute for Transfusion Medicine, University Hospital Leipzig, Leipzig, Germany
| | - Reinhard Henschler
- Institute for Transfusion Medicine, University Hospital Leipzig, Leipzig, Germany
| | - Tom H Lindner
- Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany
| | - Jan Halbritter
- Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany.,Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Ilias Doxiadis
- Institute for Transfusion Medicine, University Hospital Leipzig, Leipzig, Germany
| | - Bernt Popp
- Institute of Human Genetics, University of Leipzig, Leipzig, Germany
| | - Johannes Münch
- Division of Nephrology, Department of Internal Medicine, University of Leipzig Medical Center, Leipzig, Germany.,Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
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Belhoste M, Allenbach G, Agius T, Meier RPH, Venetz JP, Corpataux JM, Schneider A, Golshayan D, Prior JO, Déglise S, Nicod-Lalonde M, Longchamp A. Role of post-transplant graft scintigraphy in kidney donation after circulatory death. FRONTIERS IN TRANSPLANTATION 2022; 1:1065415. [PMID: 38994379 PMCID: PMC11235226 DOI: 10.3389/frtra.2022.1065415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 11/29/2022] [Indexed: 07/13/2024]
Abstract
Background There is no consensus on how to predict post-transplant function of donation after circulatory death (DCD) kidneys. Thus, we aimed to identify renal scintigraphy parameters that could predict 1-year kidney function. Methods In this single center study, we included all consecutive DCD kidney recipients between 2013 and 2021 (n = 29). Patients who did not have a scintigraphy within 10 days of transplantation (n = 3), recipients of multiple organs and less than 18 years old were excluded (n = 1). Primary endpoint was the estimated glomerular filtration rate (eGFR). Results Median eGFR and serum creatinine at 1 year were 67 µmol/L (56-81) and 111 ml/min (99-132), respectively. Among parameters tested, the 3rd/2nd-minute activity ratio had the best diagnostic performance (AUC: 0.74 and 0.71, for eGFR and creatinine) 1 year post transplantation. Using 1.21 as the best cut off, the 3rd/2nd-minute activity ratio specificity and sensitivity to predict eGFR >60 ml/min was 0.82 and 0.83. Renal function was significantly better at 1 week, 3, 6, and 12 months after transplantation in patients with 3rd/2nd-minute activity ratios above 1.21. Conclusion This study suggests that the 3rd/2nd-minute activity ratio can predict graft function at 1 year. The benefit of post-transplant scintigraphy should be further validated in a prospective cohort.
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Affiliation(s)
- Manon Belhoste
- Department of Vascular Surgery, Lausanne University Hospital, Lausanne, Switzerland
| | - Gilles Allenbach
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Thomas Agius
- Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland
| | - Raphael P. H. Meier
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Jean-Pierre Venetz
- Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland
| | - Jean-Marc Corpataux
- Department of Vascular Surgery, Lausanne University Hospital, Lausanne, Switzerland
| | - Antoine Schneider
- Adult Intensive Care Unit, Lausanne University Hospital, Lausanne, Switzerland
| | - Déla Golshayan
- Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland
| | - John O. Prior
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Sébastien Déglise
- Department of Vascular Surgery, Lausanne University Hospital, Lausanne, Switzerland
| | - Marie Nicod-Lalonde
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Alban Longchamp
- Department of Vascular Surgery, Lausanne University Hospital, Lausanne, Switzerland
- Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland
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31
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Zhang F, Liang J, Xiong Y, Zhang F, Wu K, Wang W, Yuan J, Lin T, Wang X. Serum uric acid as a risk factor for rejection after deceased donor kidney transplantation: A mono-institutional analysis of paired kidneys. Front Immunol 2022; 13:973425. [PMID: 36578496 PMCID: PMC9791182 DOI: 10.3389/fimmu.2022.973425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 11/23/2022] [Indexed: 12/14/2022] Open
Abstract
Background Deceased donor kidney transplantation (DDKT) is a major therapeutic option for patients with end-stage renal diseases. Although medical techniques improved in recent years, acute or chronic rejection after DDKT is not uncommon and often results in poor graft survival. Therefore, the determination of risk factors is very important to stratify patients and to improve outcomes. This study aims to evaluate the risk factors for treated rejection (TR) of patients after DDKT. Methods Clinical data of deceased donors and corresponding recipients were retrospectively collected. The primary outcome was TR defined as the treatment for rejection within 24 months after DDKT. Univariate comparisons of baseline characteristics were performed with Chi-square test, t-test, and Mann-Whitney U test. Logistic regression was constructed to analyze potential risk factors. Receiver operating characteristic (ROC) curve and Jordan index were generated to determine the optimal cutoff value. The association between continuous variables and TR was examined and visualized by using restricted cubic spline (RCS) models. Results Data of 123 deceased donors and 246 recipients were obtained and analyzed. The median age was 41 (4-62) years for recipients and 39 (1-65) years for donors. The recipients who died or suffered graft loss during the follow-up period were 8 (3.3%) and 12 (4.9%), respectively. After univariate analysis and subsequent multivariate analysis, the preoperative serum uric acid (OR, 2.242; 95% CI, 1.037-4.844; P = 0.040), platelet (OR, 2.163; 95% CI, 1.073-4.361, P = 0.031), absolute neutrophil count (OR, 2.183; 95% CI, 1.025-4.649; P = 0.043), and HLA-DQ mismatch (OR, 2.102; 95% CI, 1.093-4.043; P = 0.026) showed statistical significance. RCS models showed that patients with higher levels of uric acid had increased risk of TR. Conclusions Serum uric acid and other three indicators were found to be the independent risk factors for TR, which may contribute to stratify patients and develop personalized regimen in perioperative period.
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Organ donation after cardiac death in Japan. TRANSPLANTATION REPORTS 2022. [DOI: 10.1016/j.tpr.2022.100114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Liu YP, Tseng CS, Chiang YJ, Chueh JS, Hsueh JY. The development and outcomes of organ transplantation from donation after circulatory death in Taiwan. TRANSPLANTATION REPORTS 2022. [DOI: 10.1016/j.tpr.2022.100113] [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] Open
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Petit V, Lenain R, Debillon F, Hazzan M, Provot F. [Association between controlled circulatory death donor waitlisting and waiting time before kidney transplantation in a French center]. Nephrol Ther 2022; 18:604-610. [PMID: 36357263 DOI: 10.1016/j.nephro.2022.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 08/25/2022] [Accepted: 09/20/2022] [Indexed: 11/09/2022]
Abstract
INTRODUCTION Transplantation from controlled donation after circulatory determination of death (cDCD) is a new practice in France. An additional specific consent is required for registration on the cDCD waiting list. The aim of this study is to evaluate the impact of cDCD acceptance on the waiting time for the registered patients on the transplant list. METHODS Patients registered on the kidney transplant waiting list for a Death Brain Donor (DBD) kidney transplant between 2018 and 2019 in our center were included. Patients who were candidates for a second kidney transplant or who had already received an organ transplant were not included. The cDCD waiting list registration was authorized by a signed consent of the patient on the day of DBD registration. The primary endpoint was time to renal transplantation. RESULTS Of the 315 patients eligible for a cDCD graft at transplant list registration, 152 were registered on the cDCD waiting list. Time to transplantation for these patients was multiplied by 1.42 (95%CI 1.07-1.87) compared with patients not registered for a cDCD graft. The time to transplantation was 2.59 months (95%CI 0.49-4.69) shorter for a 2-year follow-up for cDCD-listed patients. This represents one additional transplant at 6 months for every seven registered patients. CONCLUSION cDCD waiting list registration reduced the time to kidney transplantation in France.
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Affiliation(s)
- Vivien Petit
- Service de néphrologie, CHU de Lille, Lille, France; Service de néphrologie, centre hospitalier de Dunkerque, 59240 Dunkerque, France.
| | - Remi Lenain
- Service de néphrologie, CHU de Lille, Lille, France; Inserm UMR 1246 - SPHERE, université de Nantes, université de Tours, Nantes, France
| | | | - Marc Hazzan
- Service de néphrologie, CHU de Lille, Lille, France
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Chetty S, Yarani R, Swaminathan G, Primavera R, Regmi S, Rai S, Zhong J, Ganguly A, Thakor AS. Umbilical cord mesenchymal stromal cells-from bench to bedside. Front Cell Dev Biol 2022; 10:1006295. [PMID: 36313578 PMCID: PMC9597686 DOI: 10.3389/fcell.2022.1006295] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 09/27/2022] [Indexed: 11/27/2022] Open
Abstract
In recent years, mesenchymal stromal cells (MSCs) have generated a lot of attention due to their paracrine and immuno-modulatory properties. mesenchymal stromal cells derived from the umbilical cord (UC) are becoming increasingly recognized as having increased therapeutic potential when compared to mesenchymal stromal cells from other sources. The purpose of this review is to provide an overview of the various compartments of umbilical cord tissue from which mesenchymal stromal cells can be isolated, the differences and similarities with respect to their regenerative and immuno-modulatory properties, as well as the single cell transcriptomic profiles of in vitro expanded and freshly isolated umbilical cord-mesenchymal stromal cells. In addition, we discuss the therapeutic potential and biodistribution of umbilical cord-mesenchymal stromal cells following systemic administration while providing an overview of pre-clinical and clinical trials involving umbilical cord-mesenchymal stromal cells and their associated secretome and extracellular vesicles (EVs). The clinical applications of umbilical cord-mesenchymal stromal cells are also discussed, especially in relation to obstacles and potential solutions for their effective translation from bench to bedside.
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Affiliation(s)
- Shashank Chetty
- Interventional Radiology Innovation at Stanford (IRIS), Stanford University, Department of Radiology, Palo Alto, CA, United States
| | - Reza Yarani
- Interventional Radiology Innovation at Stanford (IRIS), Stanford University, Department of Radiology, Palo Alto, CA, United States
- Translational Type 1 Diabetes Research, Department of Clinical, Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - Ganesh Swaminathan
- Interventional Radiology Innovation at Stanford (IRIS), Stanford University, Department of Radiology, Palo Alto, CA, United States
| | - Rosita Primavera
- Interventional Radiology Innovation at Stanford (IRIS), Stanford University, Department of Radiology, Palo Alto, CA, United States
| | - Shobha Regmi
- Interventional Radiology Innovation at Stanford (IRIS), Stanford University, Department of Radiology, Palo Alto, CA, United States
| | - Sravanthi Rai
- Interventional Radiology Innovation at Stanford (IRIS), Stanford University, Department of Radiology, Palo Alto, CA, United States
| | - Jim Zhong
- Department of Diagnostic and Interventional Radiology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Abantika Ganguly
- Interventional Radiology Innovation at Stanford (IRIS), Stanford University, Department of Radiology, Palo Alto, CA, United States
| | - Avnesh S Thakor
- Interventional Radiology Innovation at Stanford (IRIS), Stanford University, Department of Radiology, Palo Alto, CA, United States
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36
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Argani H. Cardiopulmonary death donation. TRANSPLANTATION REPORTS 2022. [DOI: 10.1016/j.tpr.2022.100104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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Sharif A. Deceased Donor Characteristics and Kidney Transplant Outcomes. Transpl Int 2022; 35:10482. [PMID: 36090778 PMCID: PMC9452640 DOI: 10.3389/ti.2022.10482] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 07/25/2022] [Indexed: 11/25/2022]
Abstract
Kidney transplantation is the therapy of choice for people living with kidney failure who are suitable for surgery. However, the disparity between supply versus demand for organs means many either die or are removed from the waiting-list before receiving a kidney allograft. Reducing unnecessary discard of deceased donor kidneys is important to maximize utilization of a scarce and valuable resource but requires nuanced decision-making. Accepting kidneys from deceased donors with heterogenous characteristics for waitlisted kidney transplant candidates, often in the context of time-pressured decision-making, requires an understanding of the association between donor characteristics and kidney transplant outcomes. Deceased donor clinical factors can impact patient and/or kidney allograft survival but risk-versus-benefit deliberation must be balanced against the morbidity and mortality associated with remaining on the waiting-list. In this article, the association between deceased kidney donor characteristics and post kidney transplant outcomes for the recipient are reviewed. While translating this evidence to individual kidney transplant candidates is a challenge, emerging strategies to improve this process will be discussed. Fundamentally, tools and guidelines to inform decision-making when considering deceased donor kidney offers will be valuable to both professionals and patients.
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Affiliation(s)
- Adnan Sharif
- Department of Nephrology and Transplantation, University Hospitals Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- *Correspondence: Adnan Sharif,
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Gerken ALH, Nowak K, Meyer A, Weiss C, Krüger B, Nawroth N, Karampinis I, Heller K, Apel H, Reissfelder C, Schwenke K, Keese M, Lang W, Rother U. Quantitative Assessment of Intraoperative Laser Fluorescence Angiography With Indocyanine Green Predicts Early Graft Function After Kidney Transplantation. Ann Surg 2022; 276:391-397. [PMID: 33394595 PMCID: PMC9259036 DOI: 10.1097/sla.0000000000004529] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
OBJECTIVE This study was designed to demonstrate the predictive ability of quantitative indocyanine green (ICG) fluorescence angiography for the short-term postoperative outcome, the occurrence of delayed graft function (DGF), and long-term graft survival. SUMMARY BACKGROUND DATA DGF is a relevant problem after kidney transplantation; sufficient microperfusion of the allograft is crucial for postoperative organ function. Fluorescence angiography with ICG can serve as an intraoperative quality control of microperfusion. METHODS This prospective diagnostic study, conducted in 2 German transplantation centers from November 2015 to October 2018, included 128 consecutive kidney transplantations. Intraoperative assessment of the allograft microperfusion was performed by near-infrared fluorescence angiography with ICG; a software was used for quantitative analysis. The associations between perfusion parameters (eg, ICG Ingress) and donor, recipient, peri-procedural, and postoperative characteristics were evaluated. RESULTS DGF occurred in 23 (24%) kidney recipients from deceased donors. ICG Ingress ( P = 0.0027), donor age ( P = 0.0452), recipient age ( P = 0.0139), and recipient body mass index ( P = 0.0017) were associated with DGF. ICG Ingress correlated significantly with recipient age (r = -0.27662, P = 0.0016), cold and warm ischemia time (r = -0.25204, P = 0.0082; r = -0.19778, P = 0.0283), operating time (r = -0.32208, P = 0.0002), eGFR on postoperative days 1 (r =+0.22674, P = 0.0104) and 7 (r = +0.33189, P = 0.0001). The cutoff value for ICG Ingress was 106.23 AU with sensitivity of 78.3% and specificity of 80.8% ( P < 0.0001) for the prediction of DGF. CONCLUSION Fluorescence angiography with ICG allows intraoperative quantitative assessment of microperfusion during kidney transplantation. The parameter ICG Ingress reflects recipient and procedure characteristics and is able to predict the incidence of DGF. TRIAL REGISTRATION Clinicaltrials.gov: NCT-02775838.
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Affiliation(s)
- Andreas L H Gerken
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Kai Nowak
- Department of Surgery, RoMed Hospital Rosenheim, Rosenheim, Germany
| | - Alexander Meyer
- Department of Vascular Surgery, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany
| | - Christel Weiss
- Department of Biometry and Statistics, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Bernd Krüger
- Department of Medicine V, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Nina Nawroth
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Ioannis Karampinis
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Katharina Heller
- Department of Nephrology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany
| | - Hendrik Apel
- Department of Urology and Pediatric Urology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany
| | - Christoph Reissfelder
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Kay Schwenke
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Michael Keese
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Werner Lang
- Department of Vascular Surgery, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany
| | - Ulrich Rother
- Department of Vascular Surgery, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany
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Lim WH, Dominguez-Gil B. Ethical Issues Related to Donation and Transplantation of Donation After Circulatory Determination of Death Donors. Semin Nephrol 2022; 42:151269. [PMID: 36577644 DOI: 10.1016/j.semnephrol.2022.07.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
With the continuing disparity between organ supply to match the increasing demand for kidney transplants in patients with renal failure, donation after the circulatory determination of death (DCDD) has become an important and increasing global source of kidneys for clinical use. The concern that the outcomes of controlled DCDD donor kidney transplants were inferior to those obtained from donors declared dead by neurologic criteria has largely diminished because large-scale registry and single-center reports consistently have reported favorable outcomes. For uncontrolled DCDD kidney transplants, outcomes are correspondingly acceptable, although there is a greater risk of primary nonfunction. The potential of DCDD remains unrealized in many countries because of the ethical concerns and resource implications in the utilization of these donor kidneys for transplantation. In this review, we discuss the origin and definitions of DCDD donors, and examine the long-term outcomes of transplants from DCDD donor kidneys. We discuss the controversies, challenges, and ethical and legal barriers in the acceptance of DCDD, including the complexities of implementing and sustaining controlled and uncontrolled DCDD donor programs. The lessons learned from global leaders will assist a wider international recognition, acceptance, and development of DCDD transplant programs that will noticeably facilitate and address the global shortages of kidneys for transplantation, and ensure the opportunity for people who had indicated their desires to become organ donors fulfill their final wishes.
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Affiliation(s)
- Wai H Lim
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia; Internal Medicine, University of Western Australia Medical School, Perth, Australia.
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Bestard O, Thaunat O, Bellini MI, Böhmig GA, Budde K, Claas F, Couzi L, Furian L, Heemann U, Mamode N, Oberbauer R, Pengel L, Schneeberger S, Naesens M. Alloimmune Risk Stratification for Kidney Transplant Rejection. Transpl Int 2022; 35:10138. [PMID: 35669972 PMCID: PMC9163827 DOI: 10.3389/ti.2022.10138] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 01/26/2022] [Indexed: 11/13/2022]
Abstract
Different types of kidney transplantations are performed worldwide, including biologically diverse donor/recipient combinations, which entail distinct patient/graft outcomes. Thus, proper immunological and non-immunological risk stratification should be considered, especially for patients included in interventional randomized clinical trials. This paper was prepared by a working group within the European Society for Organ Transplantation, which submitted a Broad Scientific Advice request to the European Medicines Agency (EMA) relating to clinical trial endpoints in kidney transplantation. After collaborative interactions, the EMA sent its final response in December 2020, highlighting the following: 1) transplantations performed between human leukocyte antigen (HLA)-identical donors and recipients carry significantly lower immunological risk than those from HLA-mismatched donors; 2) for the same allogeneic molecular HLA mismatch load, kidney grafts from living donors carry significantly lower immunological risk because they are better preserved and therefore less immunogenic than grafts from deceased donors; 3) single-antigen bead testing is the gold standard to establish the repertoire of serological sensitization and is used to define the presence of a recipient's circulating donor-specific antibodies (HLA-DSA); 4) molecular HLA mismatch analysis should help to further improve organ allocation compatibility and stratify immunological risk for primary alloimmune activation, but without consensus regarding which algorithm and cut-off to use it is difficult to integrate information into clinical practice/study design; 5) further clinical validation of other immune assays, such as those measuring anti-donor cellular memory (T/B cell ELISpot assays) and non-HLA-DSA, is needed; 6) routine clinical tests that reliably measure innate immune alloreactivity are lacking.
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Affiliation(s)
- Oriol Bestard
- Department of Nephrology and Kidney Transplantation, Vall d'Hebrón University Hospital, Barcelona, Spain
| | - Olivier Thaunat
- Department of Transplantation, Nephrology, and Clinical Immunology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
| | | | - Georg A Böhmig
- Department of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Frans Claas
- Eurotransplant Reference Laboratory, Department of Immunology, Leiden University Medical Center, Leiden, Netherlands
| | - Lionel Couzi
- Department of Nephrology, Transplantation and Dialysis, Bordeaux University Hospital, Bordeaux, France
| | - Lucrezia Furian
- Kidney and Pancreas Transplantation Unit, University of Padua, Padua, Italy
| | - Uwe Heemann
- Department of Nephrology, Technical University of Munich, Munich, Germany
| | - Nizam Mamode
- Department of Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
| | - Rainer Oberbauer
- Department of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | - Liset Pengel
- Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - Stefan Schneeberger
- Department of General, Transplant, and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Maarten Naesens
- Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium
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Naesens M, Loupy A, Hilbrands L, Oberbauer R, Bellini MI, Glotz D, Grinyó J, Heemann U, Jochmans I, Pengel L, Reinders M, Schneeberger S, Budde K. Rationale for Surrogate Endpoints and Conditional Marketing Authorization of New Therapies for Kidney Transplantation. Transpl Int 2022; 35:10137. [PMID: 35669977 PMCID: PMC9163307 DOI: 10.3389/ti.2022.10137] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 03/10/2022] [Indexed: 12/13/2022]
Abstract
Conditional marketing authorization (CMA) facilitates timely access to new drugs for illnesses with unmet clinical needs, such as late graft failure after kidney transplantation. Late graft failure remains a serious, burdensome, and life-threatening condition for recipients. This article has been developed from content prepared by members of a working group within the European Society for Organ Transplantation (ESOT) for a Broad Scientific Advice request, submitted by ESOT to the European Medicines Agency (EMA), and reviewed by the EMA in 2020. The article presents the rationale for using surrogate endpoints in clinical trials aiming at improving late graft failure rates, to enable novel kidney transplantation therapies to be considered for CMA and improve access to medicines. The paper also provides background data to illustrate the relationship between primary and surrogate endpoints. Developing surrogate endpoints and a CMA strategy could be particularly beneficial for studies where the use of primary endpoints would yield insufficient statistical power or insufficient indication of long-term benefit following transplantation.
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Affiliation(s)
- Maarten Naesens
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- *Correspondence: Maarten Naesens,
| | - Alexandre Loupy
- Paris Translational Research Center for Organ Transplantation, Hôpital Necker, Paris, France
| | - Luuk Hilbrands
- Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Rainer Oberbauer
- Department of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | | | - Denis Glotz
- Paris Translational Research Center for Organ Transplantation, Hôpital Saint Louis, Paris, France
| | | | - Uwe Heemann
- Department of Nephrology, Technical University of Munich, Munich, Germany
| | - Ina Jochmans
- Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Liset Pengel
- Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - Marlies Reinders
- Erasmus MC Transplant Institute, Department of Internal Medicine, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Stefan Schneeberger
- Department of General, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
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Abstract
The wait list for organ transplant exceeds the rate of organ donation, especially in children. The solid-organ transplant rate has remained stable over time, despite increased demand. Although donation after cardiac death has helped to expand the donor organ pool for the adult population, this option remains scarce for children in need of transplant. Because long-term graft survival is more important in the pediatric group than in adults, we should reconsider the common notion that donation after cardiac death is inferior to donation after brain death. Herein, we review the literature to extract and analyze data regarding donation after cardiac death for solid-organ transplant in children.
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Affiliation(s)
- Hassan Argani
- From the Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Recent Methods of Kidney Storage and Therapeutic Possibilities of Transplant Kidney. Biomedicines 2022; 10:biomedicines10051013. [PMID: 35625750 PMCID: PMC9139114 DOI: 10.3390/biomedicines10051013] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 04/24/2022] [Accepted: 04/25/2022] [Indexed: 11/21/2022] Open
Abstract
Kidney transplantation is the standard procedure for the treatment of end-stage renal disease (ESRD). During kidney storage and before implantation, the organ is exposed to damaging factors which affect the decline in condition. The arrest of blood circulation results in oxygen and nutrient deficiency that lead to changes in the cell metabolism from aerobic to anaerobic, damaging organelles and cell structures. Currently, most kidney grafts are kept in a cold preservation solution to preserve low metabolism. However, there are numerous reports that machine perfusion is a better solution for organ preservation before surgery. The superiority of machine perfusion was proved in the case of marginal donor grafts, such as extended criteria donors (ECD) and donation after circulatory death (DCD). Different variant of kidney machine perfusions are evaluated. Investigators look for optimal conditions to protect kidneys from ischemia-reperfusion damage consequences by examining the best temperature conditions and comparing systems with constant or pulsatile flow. Moreover, machine perfusion brings additional advantages in clinical practice. Unlike cold static storage, machine perfusion allows the monitoring of the parameters of organ function, which gives a real possibility to make a decision prior to transplantation concerning whether the kidney is suitable for implantation. Moreover, new pharmacological therapies are sought to minimize organ damage. New components or cellular therapies can be applied, since perfusion solution flows through the organ. This review outlines the pros and cons of each machine perfusion technique and summarizes the latest achievements in the context of kidney transplantation using machine perfusion systems.
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Fang X, Chen S, Fu J, Liu R, Dai T, Wang D, Wu W, Yang S. Risk factors for renal allograft survival with China novel donation category: Donation after brain death followed by cardiac arrest. Transpl Immunol 2022; 72:101591. [PMID: 35364244 DOI: 10.1016/j.trim.2022.101591] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 03/24/2022] [Accepted: 03/25/2022] [Indexed: 11/17/2022]
Abstract
INTRODUCTION To meet the need for transplantable organs, a new donation program was initiated by the Chinese government. This novel policy created three categories for deceased organ donations: donation after circulatory death cardiac death (DCD), donation after brain death (DBD), and donation after brain death followed by circulatory death (DBCD) meaning complete cardiac arrest. In fact, the DBCD method is a combination of both DBD and DCD methods. A DBCD donor meets the criteria of for brain death, but the organ procurement begins after the withdrawal of life support and the subsequent cardiac arrest death. The purpose of this study was to evaluate the long-term outcomes of kidney transplantation in our center with the DBCD policy. Potential risk factors for affecting the renal allograft survival were also analyzed based on our data. METHOD A retrospective study, involving 421 kidney transplants derived from 214 donors, was conducted between December 2011 and October 2019. In particular, 373 (88.6%) transplanted organs met the criteria for DBCD, and 48 (11.4%) for DCD. The log-rank test was used to compare the difference in survival. The Cox regression analysis was used for risk factor screening. RESULT Analysis showed that the DBCD group was better than the DCD group in terms of overall (p = 0.031) as well as death-censored (p = 0.026) allograft survival using the log-rank test. A Cox regression analysis revealed that increasing donor age (p = 0.002, HR = 1.820/10 years incremental older), increasing recipient age (p = 0.028, HR = 1.521/10 years increment older), prolonged dialysis duration (p = 0.007, HR = 1.018), occurrence episodes of acute rejection (p = 0.016, HR = 2.697), delayed graft function (p = 0.012, HR = 2.962), mismatch ≥4 HLA loci (p = 0.038, HR = 3.606), and warm ischemia time > 15 min (p = 0.022, HR = 2.915), were all independent risk factors affecting the graft survival. CONCLUSION The new DBCD policy of donation produced acceptable results similar or even better than the DCD practice. Based on our analysis, the graft survival of DBCD transplants may be better than DCD transplants. The main risk factors for allograft loss included an increasing donor age, recipient age, warm ischemia time > 15 min, prolonged dialysis duration, acute rejection, delayed graft function, and HLA mismatch ≥4 HLA loci.
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Affiliation(s)
- Xiao Fang
- Department of Kidney Transplantation, the 900th Hospital of the People's Liberation Army Joint Service Support Force, No.156 Xi'erhuan North Road, Fuzhou 350025, China; Department of Urology, MengChao Hepatobiliary Hospital of Fujian Medical University, No.312 Xihong Road, Fuzhou 350001, China
| | - Shushang Chen
- Department of Kidney Transplantation, the 900th Hospital of the People's Liberation Army Joint Service Support Force, No.156 Xi'erhuan North Road, Fuzhou 350025, China; Department of Urology, Affiliated Tumor Hospital of Fujian medical university, Fujian Provincial Tumor Hospital, Fuzhou 350011, Fujian, China
| | - Junmin Fu
- Department of Kidney Transplantation, the 900th Hospital of the People's Liberation Army Joint Service Support Force, No.156 Xi'erhuan North Road, Fuzhou 350025, China
| | - Rong Liu
- Department of Kidney Transplantation, the 900th Hospital of the People's Liberation Army Joint Service Support Force, No.156 Xi'erhuan North Road, Fuzhou 350025, China
| | - Tianzeng Dai
- Department of Kidney Transplantation, the 900th Hospital of the People's Liberation Army Joint Service Support Force, No.156 Xi'erhuan North Road, Fuzhou 350025, China; Fuzong Clinical Medical College of Fujian Medical University, No.156 Xi'erhuan North Road, Fuzhou 350025, China
| | - Dong Wang
- Department of Kidney Transplantation, the 900th Hospital of the People's Liberation Army Joint Service Support Force, No.156 Xi'erhuan North Road, Fuzhou 350025, China; Fuzong Clinical Medical College of Fujian Medical University, No.156 Xi'erhuan North Road, Fuzhou 350025, China
| | - Weizhen Wu
- Department of Kidney Transplantation, the 900th Hospital of the People's Liberation Army Joint Service Support Force, No.156 Xi'erhuan North Road, Fuzhou 350025, China; Fuzong Clinical Medical College of Fujian Medical University, No.156 Xi'erhuan North Road, Fuzhou 350025, China.
| | - Shunliang Yang
- Department of Kidney Transplantation, the 900th Hospital of the People's Liberation Army Joint Service Support Force, No.156 Xi'erhuan North Road, Fuzhou 350025, China; Fuzong Clinical Medical College of Fujian Medical University, No.156 Xi'erhuan North Road, Fuzhou 350025, China.
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Amelioration of Renal Injury by Resveratrol in a Rat Renal Transplantation Model via Activation of the SIRT1/NF-κB Signaling Pathway. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7140961. [PMID: 35386302 PMCID: PMC8979694 DOI: 10.1155/2022/7140961] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 02/22/2022] [Accepted: 03/02/2022] [Indexed: 11/17/2022]
Abstract
Purpose. The improvement of the long-term survival of patients receiving kidney transplantation remains challenging. Ischemia reperfusion injury (IRI) reduces long-term renal graft survival in the early posttransplantation phase. However, few studies have investigated the effects of IRI on the pathogenesis of chronic renal graft failure. Silent information regulator 1 (SIRT1) regulates antioxidative stress and inflammatory response and protects against IRI. This study is aimed at investigating the role of resveratrol (RSV), an SIRT1 activator, in preventing renal injury in a rat renal transplantation model. Methods. A classical F334-to-LEW orthotopic renal transplantation rat model was established. The experiment group was treated with RSV from three days prior to kidney transplantation and the treatment lasted until the day of harvest. Uninephrectomized F344 and Lewis rats were used as controls. After 12 weeks, the effects of RSV were evaluated according to renal function, histopathology, immunohistochemistry, and western blotting. The activities of oxidative stress-related markers and proinflammatory cytokines were also assessed. Results. RSV treatment significantly ameliorated renal function and histopathological lesions in kidney-transplanted rats and increased the levels of GSH, SOD, and CAT and decreased the levels of MDA and iNOS. Furthermore, RSV also inhibited the expression of proinflammatory cytokines/chemokines such as TNF-α, CD68, and IL-6 in kidney-transplanted rats. In addition, the transplant group displayed significantly lower level of SIRT1 and higher level of Ac-NF-κBp65. RSV increased the expression of SIRT1 and decreased the expression of Ac-NF-κBp65. Conclusion. SIRT1 plays an important role in the pathogenesis of chronic renal allograft dysfunction. It is a potential therapeutic agent for ameliorating inflammation and oxidative stress-induced renal injury following kidney transplantation by activating the SIRT1/NF-κB signaling pathway.
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van de Laar SC, Lafranca JA, Minnee RC, Papalois V, Dor FJMF. The Impact of Cold Ischaemia Time on Outcomes of Living Donor Kidney Transplantation: A Systematic Review and Meta-Analysis. J Clin Med 2022; 11:1620. [PMID: 35329945 PMCID: PMC8951281 DOI: 10.3390/jcm11061620] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 03/04/2022] [Accepted: 03/09/2022] [Indexed: 02/04/2023] Open
Abstract
Studies have been carried out to investigate the effect of a prolonged cold ischaemia time (CIT) on the outcomes of living donor kidney transplantation (LDKT). There is no clear consensus in the literature about the effects of CIT on LDKT outcomes, and therefore, we performed a systematic review and meta-analysis to provide evidence on this subject. Searches were performed in five databases up to 12 July 2021. Articles comparing different CIT in LDKT describing delayed graft function (DGF), graft and patient survival, and acute rejection were considered for inclusion. This study is registered with PROSPERO, CRD42019131438. In total, 1452 articles were found, of which eight were finally eligible, including a total of 164,179 patients. Meta-analyses showed significantly lower incidence of DGF (odds ratio (OR) = 0.61, p < 0.01), and significantly higher 1-year graft survival (OR = 0.72, p < 0.001) and 5-year graft survival (OR = 0.88, p = 0.04), for CIT of less than 4 h. Our results underline the need to keep CIT as short as possible in LDKT (ideally < 4 h), as a shorter CIT in LDKT is associated with a statistically significant lower incidence of DGF and higher graft survival compared to a prolonged CIT. However, clinical impact seems limited, and therefore, in LDKT programmes in which the CIT might be prolonged, such as kidney exchange programmes, the benefits outweigh the risks. To minimize these risks, it is worth considering including CIT in kidney allocation algorithms and in general take precautions to protect high risk donor/recipient combinations.
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Affiliation(s)
- Stijn C. van de Laar
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London W12 0HS, UK; (S.C.v.d.L.); (J.A.L.); (V.P.)
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, 3015 CN Rotterdam, The Netherlands;
| | - Jeffrey A. Lafranca
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London W12 0HS, UK; (S.C.v.d.L.); (J.A.L.); (V.P.)
| | - Robert C. Minnee
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, 3015 CN Rotterdam, The Netherlands;
| | - Vassilios Papalois
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London W12 0HS, UK; (S.C.v.d.L.); (J.A.L.); (V.P.)
- Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
| | - Frank J. M. F. Dor
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London W12 0HS, UK; (S.C.v.d.L.); (J.A.L.); (V.P.)
- Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
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Kizilbash SJ, Evans MD, Chavers BM. Survival Benefit of Donation After Circulatory Death Kidney Transplantation in Children Compared With Remaining on the Waiting List for a Kidney Donated After Brain Death. Transplantation 2022; 106:575-583. [PMID: 33654002 PMCID: PMC8408288 DOI: 10.1097/tp.0000000000003733] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Kidneys donated after circulatory death (DCD) are increasingly being used for transplantation in adults to alleviate organ shortage. Pediatric data on survival benefits of DCD transplantation compared with remaining on the waitlist for a kidney donated after brain death (DBD) offer are lacking. METHODS We used Scientific Registry of Transplant Recipients to identify 285 pediatric (<18 y) DCD kidney transplants performed between 1987 and 2017. Propensity score matching was used to create a comparison group of 1132 DBD transplants. We used sequential Cox analysis to evaluate survival benefit of DCD transplantation versus remaining on the waitlist and Cox regression to evaluate patient and graft survival. RESULTS DCD transplantation was associated with a higher incidence of delayed graft function (adjusted odds ratio: 3.0; P < 0.001). The risks of graft failure (adjusted hazard ratio [aHR], 0.89; P = 0.46) and death (aHR, 1.2; P = 0.67) were similar between DCD and DBD recipients. We found a significant survival benefit of DCD transplantation compared with remaining on the waitlist awaiting a DBD kidney (aHR, 0.44; P = 0.03). CONCLUSIONS Despite a higher incidence of delayed graft function, long-term patient and graft survival are similar between pediatric DCD and DBD kidney transplant recipients. DCD transplantation in children is associated with a survival benefit, despite pediatric priority for organ allocation, compared with remaining on the waitlist.
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Affiliation(s)
| | - Michael D Evans
- Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN
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Mudalige NL, Callaghan CJ, Marks SD. Time to Improve the Utilization of Kidneys From Donation After Circulatory Death Donors in Pediatric Transplantation. Transplantation 2022; 106:453-454. [PMID: 33654001 DOI: 10.1097/tp.0000000000003734] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Affiliation(s)
- Nadeesha L Mudalige
- NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Chris J Callaghan
- Department of Nephrology and Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
| | - Stephen D Marks
- NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.,Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, United Kingdom
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Chaudhry D, Chaudhry A, Peracha J, Sharif A. Survival for waitlisted kidney failure patients receiving transplantation versus remaining on waiting list: systematic review and meta-analysis. BMJ 2022; 376:e068769. [PMID: 35232772 PMCID: PMC8886447 DOI: 10.1136/bmj-2021-068769] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/19/2022] [Indexed: 01/23/2023]
Abstract
OBJECTIVES To investigate the survival benefit of transplantation versus dialysis for waitlisted kidney failure patients with a priori stratification. DESIGN Systematic review and meta-analysis. DATA SOURCES Online databases MEDLINE, Ovid Embase, Web of Science, Cochrane Collection, and ClinicalTrials.gov were searched between database inception and 1 March 2021. INCLUSION CRITERIA All comparative studies that assessed all cause mortality for transplantation versus dialysis in patients with kidney failure waitlisted for transplant surgery were included. Two independent reviewers extracted the data and assessed the risk of bias of included studies. Meta-analysis was done using the DerSimonian-Laird random effects model, with heterogeneity investigated by subgroup analyses, sensitivity analyses, and meta-regression. RESULTS The search identified 48 observational studies with no randomised controlled trials (n=1 245 850 patients). In total, 92% (n=44/48) of studies reported a long term (at least one year) survival benefit associated with transplantation compared with dialysis. However, 11 of those studies identified stratums in which transplantation offered no statistically significant benefit over remaining on dialysis. In 18 studies suitable for meta-analysis, kidney transplantation showed a survival benefit (hazard ratio 0.45, 95% confidence interval 0.39 to 0.54; P<0.001), with significant heterogeneity even after subgroup/sensitivity analyses or meta-regression analysis. CONCLUSION Kidney transplantation remains the superior treatment modality for most patients with kidney failure to reduce all cause mortality, but some subgroups may lack a survival benefit. Given the continued scarcity of donor organs, further evidence is needed to better inform decision making for patients with kidney failure. STUDY REGISTRATION PROSPERO CRD42021247247.
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Affiliation(s)
- Daoud Chaudhry
- School of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Abdullah Chaudhry
- School of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Javeria Peracha
- Department of Nephrology and Transplantation, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK
| | - Adnan Sharif
- Department of Nephrology and Transplantation, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
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Kuhn C, Born A, Karolin A, Lang B, Binet I, Golshayan D, Haidar F, Müller T, Schaub S, Immer F, Koller M, Sidler D. Relevance of deceased donor proteinuria for kidney transplantation: a comprehensive national cohort study. Clin Transplant 2022; 36:e14574. [DOI: 10.1111/ctr.14574] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 12/24/2021] [Accepted: 12/25/2021] [Indexed: 11/30/2022]
Affiliation(s)
| | - Alex Born
- Klinik für Nephrologie und Hypertonie Inselspital Bern
| | | | | | - Isabelle Binet
- Klinik für Nephrologie und Transplantationsmedizin, Kantonsspital St. Gallen St. Gallen
| | - Délaviz Golshayan
- Centre de transplantation d'organes et Service de néphrologie Centre hospitalier universitaire vaudois Lausanne
| | - Fadi Haidar
- Service de néphrologie et hypertension hôpitaux universitaires Genève Genève
| | - Thomas Müller
- Klinik für Nephrologie Universitätsspital Zürich Zürich
| | - Stefan Schaub
- Klinik für Transplantationsimmunologie und Nephrologie Universitätsspital Basel Basel
| | | | - Michael Koller
- Klinik für Transplantationsimmunologie und Nephrologie Universitätsspital Basel Basel
| | - Daniel Sidler
- Klinik für Nephrologie und Hypertonie Inselspital Bern
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