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1
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Carré J, Kerforne T, Hauet T, Macchi L. Tissue Injury Protection: The Other Face of Anticoagulant Treatments in the Context of Ischemia and Reperfusion Injury with a Focus on Transplantation. Int J Mol Sci 2023; 24:17491. [PMID: 38139319 PMCID: PMC10743711 DOI: 10.3390/ijms242417491] [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: 11/17/2023] [Revised: 12/06/2023] [Accepted: 12/10/2023] [Indexed: 12/24/2023] Open
Abstract
Organ transplantation has enhanced the length and quality of life of patients suffering from life-threatening organ failure. Donors deceased after brain death (DBDDs) have been a primary source of organs for transplantation for a long time, but the need to find new strategies to face organ shortages has led to the broadening of the criteria for selecting DBDDs and advancing utilization of donors deceased after circulatory death. These new sources of organs come with an elevated risk of procuring organs of suboptimal quality. Whatever the source of organs for transplant, one constant issue is the occurrence of ischemia-reperfusion (IR) injury. The latter results from the variation of oxygen supply during the sequence of ischemia and reperfusion, from organ procurement to the restoration of blood circulation, triggering many deleterious interdependent processes involving biochemical, immune, vascular and coagulation systems. In this review, we focus on the roles of thrombo-inflammation and coagulation as part of IR injury, and we give an overview of the state of the art and perspectives on anticoagulant therapies in the field of transplantation, discussing benefits and risks and proposing a strategic guide to their use during transplantation procedures.
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Affiliation(s)
- Julie Carré
- Service D’Hématologie Biologique, Centre Hospitalo-Universitaire de Poitiers, 86000 Poitiers, France;
- INSERM 1313 Ischémie Reperfusion, Métabolisme, Inflammation Stérile en Transplantation (IRMETIST), Université de Poitiers, 86000 Poitiers, France; (T.K.); (T.H.)
| | - Thomas Kerforne
- INSERM 1313 Ischémie Reperfusion, Métabolisme, Inflammation Stérile en Transplantation (IRMETIST), Université de Poitiers, 86000 Poitiers, France; (T.K.); (T.H.)
- Service D’Anesthésie-Réanimation et Médecine Péri-Opératoire, Centre Hospitalo-Universitaire de Poitiers, 86000 Poitiers, France
- FHU Survival Optimization in Organ Transplantation (SUPORT), 86000 Poitiers, France
| | - Thierry Hauet
- INSERM 1313 Ischémie Reperfusion, Métabolisme, Inflammation Stérile en Transplantation (IRMETIST), Université de Poitiers, 86000 Poitiers, France; (T.K.); (T.H.)
- FHU Survival Optimization in Organ Transplantation (SUPORT), 86000 Poitiers, France
- Service de Biochimie, Centre Hospitalo-Universitaire de Poitiers, 86000 Poitiers, France
| | - Laurent Macchi
- Service D’Hématologie Biologique, Centre Hospitalo-Universitaire de Poitiers, 86000 Poitiers, France;
- INSERM 1313 Ischémie Reperfusion, Métabolisme, Inflammation Stérile en Transplantation (IRMETIST), Université de Poitiers, 86000 Poitiers, France; (T.K.); (T.H.)
- FHU Survival Optimization in Organ Transplantation (SUPORT), 86000 Poitiers, France
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Thongprayoon C, Jadlowiec CC, Kaewput W, Vaitla P, Mao SA, Mao MA, Leeaphorn N, Qureshi F, Pattharanitima P, Qureshi F, Acharya PC, Nissaisorakarn P, Cooper M, Cheungpasitporn W. Distinct Phenotypes of Kidney Transplant Recipients in the United States with Limited Functional Status as Identified through Machine Learning Consensus Clustering. J Pers Med 2022; 12:859. [PMID: 35743647 PMCID: PMC9225038 DOI: 10.3390/jpm12060859] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 05/22/2022] [Accepted: 05/23/2022] [Indexed: 01/27/2023] Open
Abstract
Background: There have been concerns regarding increased perioperative mortality, length of hospital stay, and rates of graft loss in kidney transplant recipients with functional limitations. The application of machine learning consensus clustering approach may provide a novel understanding of unique phenotypes of functionally limited kidney transplant recipients with distinct outcomes in order to identify strategies to improve outcomes. Methods: Consensus cluster analysis was performed based on recipient-, donor-, and transplant-related characteristics in 3205 functionally limited kidney transplant recipients (Karnofsky Performance Scale (KPS) < 40% at transplant) in the OPTN/UNOS database from 2010 to 2019. Each cluster’s key characteristics were identified using the standardized mean difference. Posttransplant outcomes, including death-censored graft failure, patient death, and acute allograft rejection were compared among the clusters Results: Consensus cluster analysis identified two distinct clusters that best represented the clinical characteristics of kidney transplant recipients with limited functional status prior to transplant. Cluster 1 patients were older in age and were more likely to receive deceased donor kidney transplant with a higher number of HLA mismatches. In contrast, cluster 2 patients were younger, had shorter dialysis duration, were more likely to be retransplants, and were more likely to receive living donor kidney transplants from HLA mismatched donors. As such, cluster 2 recipients had a higher PRA, less cold ischemia time, and lower proportion of machine-perfused kidneys. Despite having a low KPS, 5-year patient survival was 79.1 and 83.9% for clusters 1 and 2; 5-year death-censored graft survival was 86.9 and 91.9%. Cluster 1 had lower death-censored graft survival and patient survival but higher acute rejection, compared to cluster 2. Conclusion: Our study used an unsupervised machine learning approach to characterize kidney transplant recipients with limited functional status into two clinically distinct clusters with differing posttransplant outcomes.
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Affiliation(s)
- Charat Thongprayoon
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA;
| | | | - Wisit Kaewput
- Department of Military and Community Medicine, Phramongkutklao College of Medicine, Bangkok 10400, Thailand
| | - Pradeep Vaitla
- Division of Nephrology, University of Mississippi Medical Center, Jackson, MS 39216, USA;
| | - Shennen A. Mao
- Division of Transplant Surgery, Mayo Clinic, Jacksonville, FL 32224, USA;
| | - Michael A. Mao
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, FL 32224, USA;
| | - Napat Leeaphorn
- Renal Transplant Program, University of Missouri-Kansas City School of Medicine/Saint Luke’s Health System, Kansas City, MO 64108, USA;
| | - Fawad Qureshi
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA;
| | - Pattharawin Pattharanitima
- Department of Internal Medicine, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand
| | - Fahad Qureshi
- School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA;
| | - Prakrati C. Acharya
- Division of Nephrology, Texas Tech Health Sciences Center El Paso, El Paso, TX 79905, USA;
| | - Pitchaphon Nissaisorakarn
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA;
| | - Matthew Cooper
- Medstar Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, DC 21042, USA;
| | - Wisit Cheungpasitporn
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA;
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3
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Apel H, Rother U, Wach S, Schiffer M, Kunath F, Wullich B, Heller K. Transplant Ureteral Stenosis after Renal Transplantation: Risk Factor Analysis. Urol Int 2021; 106:518-526. [PMID: 34781290 DOI: 10.1159/000519787] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 09/16/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION The results of kidney transplants have improved dramatically in recent years, leading to reduced morbidity and mortality. Despite continuous improvements, urological complications occur at a rate of 2.6%-15%. Ureteral stenosis of graft ureters is the most common complication, with a probability of 0.5%-6.3%. This study aimed to determine the incidence of ureteral stenosis after kidney transplantation and identify risk factors that distinguish transplant patients with and without ureteral stenosis. METHODS This study retrospectively analyzed patients who had undergone kidney transplantation at the Department of Urology of the Friedrich-Alexander University Erlangen-Nuremberg between 2001 and 2015. Forty-seven patients developed ureteral stenosis during the operation. Most of the ureteral stenosis cases occurred in the first 4 months after transplantation. Kaplan-Meier analysis and the log-rank test were used to calculate the cumulative risk, and the Mann-Whitney U test was used nonparametrically. The significance level was set at p < 0.05. RESULTS Statistical analysis showed that residual diuresis (p = 0.008), cold ischemia time (CIT) (p = 0.040), the body mass index (p = 0.027), and donor serum creatinine value (p = 0.039) showed a significantly different distribution between recipients with or without ureteral stenosis after kidney transplantation. In multivariate Cox's regression modeling, residual diuresis and the donor serum creatinine level were identified as the only independent predictors of patients' stenosis-free survival. CONCLUSION Urological complications not diagnosed and treated in time endanger the success of kidney transplantation. After evaluating the kidney transplantation data of the patients at the Transplant Center Erlangen-Nuremberg from 2001 to 2015, residual diuresis, CIT, the body mass index, and donor serum creatinine value were found to influence the development of ureteral stenosis.
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Affiliation(s)
- Hendrik Apel
- Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.,Transplant Centre Erlangen-Nürnberg, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Ulrich Rother
- Transplant Centre Erlangen-Nürnberg, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.,Department of Surgery, Vascular Surgery Section, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Sven Wach
- Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Mario Schiffer
- Transplant Centre Erlangen-Nürnberg, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.,Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Frank Kunath
- Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.,Transplant Centre Erlangen-Nürnberg, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Bernd Wullich
- Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.,Transplant Centre Erlangen-Nürnberg, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Katharina Heller
- Transplant Centre Erlangen-Nürnberg, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.,Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
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4
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Eleftheriadis T, Pissas G, Crespo M, Nikolaou E, Liakopoulos V, Stefanidis I. A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion. Int J Mol Sci 2021; 22:1733. [PMID: 33572206 PMCID: PMC7915934 DOI: 10.3390/ijms22041733] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 02/03/2021] [Accepted: 02/06/2021] [Indexed: 02/08/2023] Open
Abstract
Direct allorecognition is the earliest and most potent immune response against a kidney allograft. Currently, it is thought that passenger donor professional antigen-presenting cells (APCs) are responsible. Further, many studies support that graft ischemia-reperfusion injury increases the probability of acute rejection. We evaluated the possible role of primary human proximal renal tubular epithelial cells (RPTECs) in direct allorecognition by CD4+ T-cells and the effect of anoxia-reoxygenation. In cell culture, we detected that RPTECs express all the required molecules for CD4+ T-cell activation (HLA-DR, CD80, and ICAM-1). Anoxia-reoxygenation decreased HLA-DR and CD80 but increased ICAM-1. Following this, RPTECs were co-cultured with alloreactive CD4+ T-cells. In T-cells, zeta chain phosphorylation and c-Myc increased, indicating activation of T-cell receptor and co-stimulation signal transduction pathways, respectively. T-cell proliferation assessed with bromodeoxyuridine assay and with the marker Ki-67 increased. Previous culture of RPTECs under anoxia raised all the above parameters in T-cells. FOXP3 remained unaffected in all cases, signifying that proliferating T-cells were not differentiated towards a regulatory phenotype. Our results support that direct allorecognition may be mediated by RPTECs even in the absence of donor-derived professional APCs. Also, ischemia-reperfusion injury of the graft may enhance the above capacity of RPTECs, increasing the possibility of acute rejection.
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Affiliation(s)
- Theodoros Eleftheriadis
- Department of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece; (G.P.); (E.N.); (V.L.); (I.S.)
| | - Georgios Pissas
- Department of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece; (G.P.); (E.N.); (V.L.); (I.S.)
| | - Marta Crespo
- Nephrology Department, Institut Hospital del Mar d’Investigacions Mèdiques, Hospital del Mar, Parc de Salut Mar, 08003 Barcelona, Spain;
| | - Evdokia Nikolaou
- Department of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece; (G.P.); (E.N.); (V.L.); (I.S.)
| | - Vassilios Liakopoulos
- Department of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece; (G.P.); (E.N.); (V.L.); (I.S.)
| | - Ioannis Stefanidis
- Department of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece; (G.P.); (E.N.); (V.L.); (I.S.)
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MERHAMETSİZ Ö, DEMİR ME. Outcomes of delayed graft function in deceased donor kidney transplantation: a single center experience. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2021. [DOI: 10.32322/jhsm.856308] [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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Chen L, Bai H, Jin H, Zhang T, Shi B, Cai M, Wang Y. Outcomes in kidney transplantation with mycophenolate mofetil-based maintenance immunosuppression in China: a large-sample retrospective analysis of a national database. Transpl Int 2020; 33:718-728. [PMID: 31868986 DOI: 10.1111/tri.13566] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 08/27/2019] [Accepted: 12/18/2019] [Indexed: 11/30/2022]
Abstract
There is no large data analysis reporting the outcome of Chinese kidney transplant patients using mycophenolate mofetil (MMF). This study analyzed 6719 patients from the Chinese Scientific Registry of Kidney Transplantation using MMF, which included 1153 from donation after cardiac death (DCD), 1271 from donation after brain and cardiac death (DBCD), and 4295 from living donor (LD). Compared with the transplants from deceased donor (DD), better outcomes including 3-year graft survival probabilities (LD = 95.8% vs. DD = 91.3%), incidence of delayed graft function (DGF, LD = 2.4% vs. DD = 17.7%), infection (LD = 10.7% vs. DD = 20.7%), graft loss (LD = 2.3% vs. DD = 6.3), and death (LD = 1.3% vs. DD = 3.2%) were shown in the LD group, with similar incidences of acute rejection (AR, LD = 3.7% vs. DD = 4.7%), hyperuricemia (LD = 21.7% vs. DD = 22.2%) within postoperative 1 year, and serum creatinine (Scr) >133 μmol/l at 1 year (LD = 18.8% vs. DD = 18.6%). Nonsignificant differences were found between the DCD and DBCD group. The 5-year survival of patient and graft in the LD group were 97.5% and 93.0%. Adjusted Cox model for graft loss showed significant associations with DGF [hazard ratio 3.7 (95% CI: 2.4, 5.8)], AR [2.8 (1.7, 4.6)], Scr >133 μmol/l at 1 year [2.6 (1.5, 4.2)], hyperuricemia [2.3 (1.6, 3.3)], and DD [1.6 (1.1, 2.4)].
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Affiliation(s)
- Liping Chen
- Kidney Transplant Quality Control Center of National Health Commission, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Hongwei Bai
- Kidney Transplant Quality Control Center of National Health Commission, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Hailong Jin
- Kidney Transplant Quality Control Center of National Health Commission, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Tianyu Zhang
- Kidney Transplant Quality Control Center of National Health Commission, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Bingyi Shi
- Kidney Transplant Quality Control Center of National Health Commission, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Ming Cai
- Kidney Transplant Quality Control Center of National Health Commission, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yudi Wang
- Kidney Transplant Quality Control Center of National Health Commission, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
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7
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Compound Effect of Kidney Donor Profile Index and Cold Ischemic Time on 1-Year Kidney Transplant Recipient Outcomes. Transplant Proc 2019; 51:3244-3251. [DOI: 10.1016/j.transproceed.2019.08.040] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 08/30/2019] [Indexed: 11/18/2022]
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8
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Blazel JW, Turk JA, Muth BL, Parajuli S. Blessing and a curse of outpatient management of delayed graft function. World J Transplant 2019; 9:58-61. [PMID: 31523628 PMCID: PMC6715577 DOI: 10.5500/wjt.v9.i4.58] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 07/13/2019] [Accepted: 08/06/2019] [Indexed: 02/05/2023] Open
Abstract
Delayed graft function (DGF) is a common complication occurring most often after deceased donor kidney transplant with several donor characteristics as well as immunologic factors that lead to its development post-transplant. These patients require dialysis and close kidney function monitoring until sufficient allograft function is achieved. This has resulted in limited options for DGF management, either prolonged hospitalization until graft function improves to the point where dialysis is no longer needed or discharge back to their home dialysis unit with periodic follow up in the transplant clinic. DGF is associated with a higher risk for acute rejection, premature graft failure, and 30-d readmission; therefore, these patients need close monitoring, immunosuppression management, and prompt allograft biopsy if prolonged DGF is observed. This may not occur if these patients are discharged back to their home dialysis unit. To address this issue, the University of Wisconsin-Madison created a clinic in 2011 specialized in outpatient DGF management. This clinic was able to successfully reduce hospital length of stay without an increase in 30-d readmission, graft loss, and patient death.
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Affiliation(s)
- Justin W Blazel
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, United States
| | - Jennifer A Turk
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, United States
| | - Brenda L Muth
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, United States
| | - Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, United States
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9
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Wei J, Wang Y, Zhang J, Wang L, Fu L, Cha BJ, Buggs J, Liu R. A mouse model of renal ischemia-reperfusion injury solely induced by cold ischemia. Am J Physiol Renal Physiol 2019; 317:F616-F622. [PMID: 31291121 DOI: 10.1152/ajprenal.00533.2018] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Transplanted kidneys usually experience several episodes of ischemia, including cold ischemia during allograft storage in preservation solution. However, previous studies focusing on cold renal ischemia were only carried out in vitro or ex vivo. In the present study, we developed and characterized an in vivo mouse model of renal ischemia-reperfusion injury (IRI) induced exclusively by cold ischemia. C57BL/6 mice underwent right kidney nephrectomy, and the left kidney was kept cool with circulating cold saline in a kidney cup, while body temperature was maintained at 37°C. We clamped the renal pedicle and flushed out the blood inside the kidney with cold saline via an opening on the renal vein. The severity of renal IRI was examined with different ischemic durations. We found that the mice with <2 h of cold ischemia exhibited no significant changes in renal function or histopathology; animals with 3 or 4 h of cold ischemia developed into mild to moderate acute kidney injury with characteristic features, including the elevation in plasma creatinine concentration and reduction in glomerular filtration rate and tubular necrosis, followed by a subsequent recovery. However, mice with 5 h of cold ischemia died in a few days with severe acute kidney injury. In summary, we generated a mouse model of renal IRI induced exclusively by cold ischemia, which mimics graft cold storage in preservation solution, and renal function can be evaluated in vivo.
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Affiliation(s)
- Jin Wei
- Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, Florida
| | - Yingliang Wang
- Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, Florida
| | - Jie Zhang
- Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, Florida
| | - Lei Wang
- Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, Florida
| | - Liying Fu
- Tampa General Hospital, Tampa, Florida
| | - Byeong J Cha
- Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, Florida
| | | | - Ruisheng Liu
- Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, Florida
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10
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Rech TH, Custódio G, Kroth LV, Henrich SF, Filho ÉMR, Crispim D, Leitão CB. Brain death-induced cytokine release is not associated with primary graft dysfunction: a cohort study. Rev Bras Ter Intensiva 2019; 31:86-92. [PMID: 30916235 PMCID: PMC6443307 DOI: 10.5935/0103-507x.20190009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 12/10/2018] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE To examine the association between donor plasma cytokine levels and the development of primary graft dysfunction of organs transplanted from deceased donors. METHODS Seventeen deceased donors and the respective 47 transplant recipients were prospectively included in the study. Recipients were divided into two groups: group 1, patients who developed primary graft dysfunction; and group 2, patients who did not develop primary graft dysfunction. Donor plasma levels of TNF, IL-6, IL-1β, and IFN-γ assessed by ELISA were compared between groups. RESULTS Sixty-nine organs were retrieved, and 48 transplants were performed. Donor plasma cytokine levels did not differ between groups (in pg/mL): TNF, group 1: 10.8 (4.3 - 30.8) versus group 2: 8.7 (4.1 - 33.1), p = 0.63; IL-6, group 1: 1617.8 (106.7 - 5361.7) versus group 2: 922.9 (161.7 - 5361.7), p = 0.56; IL-1β, group 1: 0.1 (0.1 - 126.1) versus group 2: 0.1 (0.1 - 243.6), p = 0.60; and IFN-γ, group 1: 0.03 (0.02 - 0.2) versus group 2: 0.03 (0.02 - 0.1), p = 0.93). Similar findings were obtained when kidney transplants were analyzed separately. CONCLUSION In this sample of transplant recipients, deceased donor plasma cytokines TNF, IL-6, IL-1β, and IFN-γ were not associated with the development of primary graft dysfunction.
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Affiliation(s)
- Tatiana Helena Rech
- Programa de Pós-Graduação em Ciências
Médicas: Endocrinologia, Universidade Federal do Rio Grande do Sul - Porto
Alegre (RS), Brasil
- Unidade de Terapia Intensiva, Hospital de Clínicas de Porto
Alegre, Universidade Federal do Rio Grande do Sul - Porto Alegre (RS), Brasil
| | - Geisiane Custódio
- Programa de Pós-Graduação em Ciências
Médicas: Endocrinologia, Universidade Federal do Rio Grande do Sul - Porto
Alegre (RS), Brasil
| | | | | | - Édison Moraes Rodrigues Filho
- Unidade de Terapia Intensiva, Hospital de Clínicas de Porto
Alegre, Universidade Federal do Rio Grande do Sul - Porto Alegre (RS), Brasil
- Unidade de Terapia Intensiva, Hospital Dom Vicente Scherer - Porto
Alegre (RS), Brasil
| | - Daisy Crispim
- Programa de Pós-Graduação em Ciências
Médicas: Endocrinologia, Universidade Federal do Rio Grande do Sul - Porto
Alegre (RS), Brasil
- Divisão de Endocrinologia, Hospital de Clínicas de
Porto Alegre, Universidade Federal do Rio Grande do Sul - Porto Alegre (RS),
Brasil
| | - Cristiane Bauermann Leitão
- Programa de Pós-Graduação em Ciências
Médicas: Endocrinologia, Universidade Federal do Rio Grande do Sul - Porto
Alegre (RS), Brasil
- Divisão de Endocrinologia, Hospital de Clínicas de
Porto Alegre, Universidade Federal do Rio Grande do Sul - Porto Alegre (RS),
Brasil
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Kidney Transplantation: Local Donor and Distant Recipient, Is It Feasible? A Retrospective Cross-Sectional Study. Nephrourol Mon 2019. [DOI: 10.5812/numonthly.88665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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12
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Nieto-Ríos JF, Ochoa-García CL, Serna-Campuzano A, Benavides-Hermosa B, Calderón-Puentes LL, Aristizabal-Alzate A, Ocampo-Kohn C, Zuluaga-Valencia G, Serna-Higuita LM. Time of Cold Ischemia and Delayed Graft Function in a Cohort of Renal Transplant Patients in a Reference Center. Indian J Nephrol 2019; 29:8-14. [PMID: 30814787 PMCID: PMC6375010 DOI: 10.4103/ijn.ijn_162_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
There are many factors involved in the delayed graft function of a renal graft, with prolonged cold ischemia time being one of the most relevant. The aim of this study is to evaluate the relationship between the time of cold ischemia and the delayed graft function, and acute rejection and graft loss at 1 year of follow-up. A retrospective cohort of 347 renal transplant patients were evaluated during the years 2009-2013. The incidence of delayed graft function was 18.4% (n = 65). The cold ischemia time was an independent risk factor for delayed graft function (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.04-1.16). By grouping the time of cold ischemia by intervals, the risk of delayed graft function was greater in the 12-18 hours group (OR 2.06, 95% CI 1.02-4.15) and in the >18 hours group (OR 3.38, 95% CI 1.57-7.27). The risk of acute rejection did not increase with longer cold ischemia (p = 0.69), and cold ischemia time was not a risk factor for renal graft loss at 1-year follow-up (hazard ratio 0.97, 95% CI 0.88-1.06). In conclusion the time of cold ischemia (>12 hours) in renal transplant recipients of optimal deceased donors increases the risk of delayed graft function; however, this does not negatively impact the results in acute rejection or graft loss in the first year of the transplant.
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Affiliation(s)
- J. F. Nieto-Ríos
- Department of Nephrology Kidney Transplant, Hospital Pablo Tobón Uribe, Medellin, Colombia
- Department of Internal Medicine, University of Antioquia, Medellin, Colombia
| | - C. L. Ochoa-García
- Department of Nephrology Kidney Transplant, Hospital Pablo Tobón Uribe, Medellin, Colombia
| | - A. Serna-Campuzano
- Deparment of Internal Medicine, Faculty of Medicine, Universidad Pontificia Bolivariana, Medellin, Colombia
| | - B. Benavides-Hermosa
- Department of Nephrology Kidney Transplant, Hospital Pablo Tobón Uribe, Medellin, Colombia
| | - L. L. Calderón-Puentes
- Department of Nephrology Kidney Transplant, Hospital Pablo Tobón Uribe, Medellin, Colombia
| | - A. Aristizabal-Alzate
- Department of Nephrology Kidney Transplant, Hospital Pablo Tobón Uribe, Medellin, Colombia
| | - C. Ocampo-Kohn
- Department of Nephrology Kidney Transplant, Hospital Pablo Tobón Uribe, Medellin, Colombia
| | - G. Zuluaga-Valencia
- Department of Nephrology Kidney Transplant, Hospital Pablo Tobón Uribe, Medellin, Colombia
- Department of Internal Medicine, University of Antioquia, Medellin, Colombia
| | - L. M. Serna-Higuita
- Faculty of Medicine, Institute for Clinical Epidemiology and Applied Biometrics, Eberhard Karls University, Tuebingen, Germany
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13
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Zhao H, Alam A, Soo AP, George AJT, Ma D. Ischemia-Reperfusion Injury Reduces Long Term Renal Graft Survival: Mechanism and Beyond. EBioMedicine 2018; 28:31-42. [PMID: 29398595 PMCID: PMC5835570 DOI: 10.1016/j.ebiom.2018.01.025] [Citation(s) in RCA: 218] [Impact Index Per Article: 31.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 01/18/2018] [Accepted: 01/20/2018] [Indexed: 01/10/2023] Open
Abstract
Ischemia-reperfusion injury (IRI) during renal transplantation often initiates non-specific inflammatory responses that can result in the loss of kidney graft viability. However, the long-term consequence of IRI on renal grafts survival is uncertain. Here we review clinical evidence and laboratory studies, and elucidate the association between early IRI and later graft loss. Our critical analysis of previous publications indicates that early IRI does contribute to later graft loss through reduction of renal functional mass, graft vascular injury, and chronic hypoxia, as well as subsequent fibrosis. IRI is also known to induce kidney allograft dysfunction and acute rejection, reducing graft survival. Therefore, attempts have been made to substitute traditional preserving solutions with novel agents, yielding promising results.
Ischaemia reperfusion injury (IRI) potentiates delayed renal graft function and causes reduction in renal graft survival IRI causes innate immune system activation, hypoxic injury, inflammation and graft vascular disease Reducing prolonged cold ischaemic time improves graft survival Novel protective strategies include mesenchymal stem cells, machine perfusion, and ex vivo preservation solution saturated with gas. Further studies are needed to investigate the long-term effects of novel ex vivo preservation agents
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Affiliation(s)
- Hailin Zhao
- Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK
| | - Azeem Alam
- Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK
| | - Aurelie Pac Soo
- Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK
| | | | - Daqing Ma
- Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK.
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14
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Tapak L, Hamidi O, Amini P, Poorolajal J. Prediction of Kidney Graft Rejection Using Artificial Neural Network. Healthc Inform Res 2017; 23:277-284. [PMID: 29181237 PMCID: PMC5688027 DOI: 10.4258/hir.2017.23.4.277] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2017] [Revised: 08/17/2017] [Accepted: 09/10/2017] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES Kidney transplantation is the best renal replacement therapy for patients with end-stage renal disease. Several studies have attempted to identify predisposing factors of graft rejection; however, the results have been inconsistent. We aimed to identify prognostic factors associated with kidney transplant rejection using the artificial neural network (ANN) approach and to compare the results with those obtained by logistic regression (LR). METHODS The study used information regarding 378 patients who had undergone kidney transplantation from a retrospective study conducted in Hamadan, Western Iran, from 1994 to 2011. ANN was used to identify potential important risk factors for chronic nonreversible graft rejection. RESULTS Recipients' age, creatinine level, cold ischemic time, and hemoglobin level at discharge were identified as the most important prognostic factors by ANN. The ANN model showed higher total accuracy (0.75 vs. 0.55 for LR), and the area under the ROC curve (0.88 vs. 0.75 for LR) was better than that obtained with LR. CONCLUSIONS The results of this study indicate that the ANN model outperformed LR in the prediction of kidney transplantation failure. Therefore, this approach is a promising classifier for predicting graft failure to improve patients' survival and quality of life, and it should be further investigated for the prediction of other clinical outcomes.
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Affiliation(s)
- Leili Tapak
- Modeling of Noncommunicable Diseases Research Center, Department of Biostatistics, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Omid Hamidi
- Department of Science, Hamedan University of Technology, Hamedan, Iran
| | - Payam Amini
- Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Jalal Poorolajal
- Research Center for Health Sciences & Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
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15
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Gheith O, Al-Otaibi T, Halim MA, Mahmoud T, Nair P, Monem MA, Al-Waheeb S, Hassan R, Nampoory N. Early Versus Late Acute Antibody-Mediated Rejection Among Renal Transplant Recipients in Terms of Response to Rituximab Therapy: A Single Center Experience. EXP CLIN TRANSPLANT 2017; 15:150-155. [PMID: 28260457 DOI: 10.6002/ect.mesot2016.p32] [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: 11/05/2022]
Abstract
OBJECTIVES There are no comparable trials concerning the use of rituximab among renal transplant recipients with acute antibody-mediated rejection. Here, we compared early and late acute antibody-mediated rejection in renal transplant recipients in terms of response to rituximab therapy. MATERIALS AND METHODS Of 1230 kidney transplants performed at Hamed Al-Essa Organ Transplant Center (Kuwait) over the past 10 years, 103 recipients developed acute antibody-mediated rejections and were subcategorized into 4 groups according to the onset of rejection and rituximab treatment. All patients received the standard treatment for acute antibody-mediated rejection according to our protocol (plasma exchange and intravenous immunoglobulin). We added rituximab to the treatment regimen in 2 groups of patients: 27 patients with early rejection (group 1) and 38 patients with late rejection (group 2). Groups 3 and 4 represented nonrituximab groups, with 20 patients with early (group 3) and 18 patients with late rejection (group 4). We compared the 4 groups regarding graft and patient outcomes. RESULTS All patients were comparable regarding patient age, sex, pretransplant type of dialysis, viral profile, type of induction, donor criteria, and pretransplant comorbidities. We observed that delayed and slow graft function were significantly higher in groups 1 and 3 (P = .016); however, we found no significant differences in the 4 groups regarding new-onset diabetes after transplant, BK viral infection, and malignancy. Graft outcomes were significantly better in groups 1 and 2 than in groups 3 and 4 (P = .028). However, patient outcomes were comparable in the 4 groups (P > .05). CONCLUSIONS Early acute antibody-mediated rejection in renal transplant recipients had significantly better outcomes when rituximab was added to the standard treatment regimen.
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Affiliation(s)
- Osama Gheith
- Urology and Nephrology Center, Mansoura University, Mansoura, Egypt; Hamed Al-Essa Organ Transplant Center, Sabah Area, Kuwait
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16
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Risk Balancing of Cold Ischemic Time against Night Shift Surgery Possibly Reduces Rates of Reoperation and Perioperative Graft Loss. J Transplant 2017; 2017:5362704. [PMID: 28203455 PMCID: PMC5288530 DOI: 10.1155/2017/5362704] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 12/04/2016] [Indexed: 12/05/2022] Open
Abstract
Background. This retrospective cohort study evaluates the advantages of risk balancing between prolonged cold ischemic time (CIT) and late night surgery. Methods. 1262 deceased donor kidney transplantations were analyzed. Multivariable regression was used to determine odds ratios (ORs) for reoperation, graft loss, delayed graft function (DGF), and discharge on dialysis. CIT was categorized according to a forward stepwise pattern ≤1h/>1h, ≤2h/>2h, ≤3h/>3h,…, ≤nh/>nh. ORs for DGF were plotted against CIT and a nonlinear regression function with best R2 was identified. First and second derivative were then implemented into the curvature formula k(x) = f′′(x)/(1 + f′(x)2)3/2 to determine the point of highest CIT-mediated risk acceleration. Results. Surgery between 3 AM and 6 AM is an independent risk factor for reoperation and graft loss, whereas prolonged CIT is only relevant for DGF. CIT-mediated risk for DGF follows an exponential pattern f(x) = A · (1 + k · e(I · x)) with a cut-off for the highest risk increment at 23.5 hours. Conclusions. The risk of surgery at 3 AM–6 AM outweighs prolonged CIT when confined within 23.5 hours as determined by a new mathematical approach to calculate turning points of nonlinear time related risks. CIT is only relevant for the endpoint of DGF but had no impact on discharge on dialysis, reoperation, or graft loss.
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17
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Weitz M, Sazpinar O, Schmidt M, Neuhaus TJ, Maurer E, Kuehni C, Parvex P, Chehade H, Tschumi S, Immer F, Laube GF. Balancing competing needs in kidney transplantation: does an allocation system prioritizing children affect the renal transplant function? Transpl Int 2016; 30:68-75. [PMID: 27732754 DOI: 10.1111/tri.12874] [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: 06/14/2016] [Revised: 07/28/2016] [Accepted: 10/07/2016] [Indexed: 12/01/2022]
Abstract
Children often merit priority in access to deceased donor kidneys by organ-sharing organizations. We report the impact of the new Swiss Organ Allocation System (SOAS) introduced in 2007, offering all kidney allografts from deceased donors <60 years preferentially to children. The retrospective cohort study included all paediatric transplant patients (<20 years of age) before (n = 19) and after (n = 32) the new SOAS (from 2001 to 2014). Estimated glomerular filtration rate (eGFR), urine protein-to-creatinine ratio (UPC), need for antihypertensive medication, waiting times to kidney transplantation (KTX), number of pre-emptive transplantations and rejections, and the proportion of living donor transplants were considered as outcome parameters. Patients after the new SOAS had significantly better eGFRs 2 years after KTX (Mean Difference, MD = 25.7 ml/min/1.73 m2 , P = 0.025), lower UPC ratios (Median Difference, MeD = -14.5 g/mol, P = 0.004), decreased waiting times to KTX (MeD = -97 days, P = 0.021) and a higher proportion of pre-emptive transplantations (Odds Ratio = 9.4, 95% CI = 1.1-80.3, P = 0.018), while the need for antihypertensive medication, number of rejections and living donor transplantations remained stable. The new SOAS is associated with improved short-term clinical outcomes and more rapid access to KTX. Despite lacking long-term research, the study results should encourage other policy makers to adopt the SOAS approach.
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Affiliation(s)
- Marcus Weitz
- University Children's Hospital Zurich, Zurich, Switzerland
| | - Onur Sazpinar
- University Children's Hospital Zurich, Zurich, Switzerland
| | - Maria Schmidt
- University Children's Hospital Zurich, Zurich, Switzerland
| | | | - Elisabeth Maurer
- Institute for Social and Preventive Medicine, Berne, Switzerland
| | - Claudia Kuehni
- Institute for Social and Preventive Medicine, Berne, Switzerland
| | | | | | | | | | - Guido F Laube
- University Children's Hospital Zurich, Zurich, Switzerland
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18
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Chaudhuri A, Gallo A, Grimm P. Pediatric deceased donor renal transplantation: An approach to decision making II. Acceptability of a deceased donor kidney for a child, a snap decision at 3 AM. Pediatr Transplant 2015; 19:785-91. [PMID: 26426405 DOI: 10.1111/petr.12582] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/08/2015] [Indexed: 11/30/2022]
Abstract
Allocation of deceased donor kidneys is based on several criteria; however, the final decision to accept or reject the offered kidney is made by the potential recipient's transplant team (surgeon/nephrologist). Several considerations including assessment of the donor quality, the HLA match between the donor and the recipient, several recipient factors, the geographical location of the recipient, and the organ all affect the decision of whether or not to finally accept the organ for a particular recipient. This decision needs to be made quickly, often on the spot. Maximizing the benefit from this scarce resource raises difficult ethical issues. The philosophies of equity and utility are often competing. This article will discuss the several considerations for the pediatric nephrologist while accepting a deceased donor kidney for a particular pediatric patient.
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Affiliation(s)
- Abanti Chaudhuri
- Department of Pediatric Nephrology, Stanford University, Stanford, CA, USA
| | - Amy Gallo
- Department of Surgery, Stanford University, Stanford, CA, USA
| | - Paul Grimm
- Department of Pediatric Nephrology, Stanford University, Stanford, CA, USA
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19
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. EXP CLIN TRANSPLANT 2015; 13. [DOI: 10.6002/ect.2015.0056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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20
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Chaudhuri A, James G, Grimm P. Whether or not to accept a deceased donor kidney offer for a pediatric patient. Pediatr Nephrol 2015; 30:1529-36. [PMID: 26130248 DOI: 10.1007/s00467-015-3139-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Revised: 05/22/2015] [Accepted: 05/27/2015] [Indexed: 12/01/2022]
Abstract
The expansion of the number of children on the deceased donor renal transplant waitlist has far outstripped the supply of organs in most countries, leading to numerous adjustments to increase supply and to maximize the utility of donor organs. The system for organ allocation varies by country based on local laws, priorities, and resources. Adjustments are made to optimize allocation, enhance post-transplant survival benefit, decrease unequal transplant access, and optimize utilization of donated kidneys. Allocation of deceased donor kidneys is based on several criteria; however, the final decision to accept or reject the offered kidney is made by the potential recipient's transplant team (surgeon/nephrologist). Several considerations including assessment of the donor quality, the human leukocyte antigen (HLA) match between the donor and the recipient, numerous recipient factors, the geographical location of the recipient, and the organ all affect the decision to accept the organ or not for a particular recipient. This decision must be made quickly, often on the spot. Maximizing the benefit from this scarce resource raises difficult ethical issues. The philosophies of equity and utility are often competing. In this manuscript, we highlight a representative case that helps to focus on important issues for the pediatric nephrologist to consider while making the decision to accept a deceased donor kidney offer for a particular pediatric patient.
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Affiliation(s)
- Abanti Chaudhuri
- Department of Pediatric Nephrology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA, 94305-5208, USA,
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