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Zaidi RA, Hubin E, Agha A, Takande S. Influence of Recipient Insurance on the Outcome of Simultaneous Pancreas and Kidney Transplantation. Transplant Proc 2025; 57:371-379. [PMID: 39890512 DOI: 10.1016/j.transproceed.2025.01.005] [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: 06/19/2024] [Revised: 12/28/2024] [Accepted: 01/15/2025] [Indexed: 02/03/2025]
Abstract
INTRODUCTION Simultaneous pancreas-kidney (SPK) transplantation is an established treatment for insulin-requiring diabetics with advanced chronic or end-stage kidney disease. Outcomes of SPK transplantation may vary according to socioeconomic factors such as funding sources. The aim of this study was to assess the association between insurance payer of transplant recipients and outcomes of SPK transplantation in the United States. METHODS All adult primary SPK transplants performed in the United States between January 1, 1988, and December 31, 2017 were included, using data from the national Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients database. A total of 19,849 adult SPK transplant recipients were included in the study, after excluding patients who had insurance sources other than Medicaid, Medicare, or private; dual insurance; or were lost at 90-day follow-up. Post-transplant outcomes were analyzed in terms of allograft and recipient survival. RESULTS Recipients with private insurance had significantly lower risks of late kidney graft loss (hazard ratio [HR], 0.74), late pancreas graft loss (HR, 0.77), and late death (HR, 0.73) compared with those with Medicaid. Recipients with Medicare had a higher risk of late death (HR, 1.05). Private insurance recipients had better 10-year and 15-year kidney, pancreas, and patient graft survival rates across most racial/ethnic groups. CONCLUSIONS Recipient insurance status significantly influenced long-term outcomes after SPK transplantation. Transplant programs should consider publicly sponsored insurance status as a marker of poorer post-transplant survival to implement changes in both pre- and post-transplant strategies.
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Affiliation(s)
- Raza Ali Zaidi
- University of Chicago Laboratory School, Chicago, Illinois.
| | | | - Ahmed Agha
- The George Washington University, Washington, DC
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Alfaro Villanueva LA, Junior RM, Rangel ÉB, Modelli LG, Viana LA, Cristelli MP, Requião-Moura L, Foresto RD, Tedesco-Silva H, Pestana JM. Assessing the influence of graft loss on 4-year patient survival after simultaneous pancreas-kidney transplantation: Kaplan-Meier versus Competing Risk Analysis model. Clin Transplant 2024; 38:e15298. [PMID: 38545918 DOI: 10.1111/ctr.15298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 02/28/2024] [Accepted: 03/11/2024] [Indexed: 04/20/2024]
Abstract
BACKGROUND Graft loss increases the risk of patient death after simultaneous pancreas-kidney (SPK) transplantation. The relative risk of each graft failure is complex due to the influence of several competing events. METHODS This retrospective, single-center study compared 4-year patient survival according to the graft status using Kaplan-Meier (KM) and Competing Risk Analysis (CRA). Patient survival was also assessed according to five eras (Era 1: 2001-2003; Era 2: 2004-2006; Era 3: 2007-2009; Era 4: 2010-2012; Era 5: 2012-2015). RESULTS Between 2000 and 2015, 432 SPK transplants were performed. Using KM, patient survival was 86.5% for patients without graft loss (n = 333), 93.4% for patients with pancreas graft loss (n = 46), 43.7% for patients with kidney graft loss (n = 16), and 25.4% for patients with pancreas and kidney graft loss (n = 37). Patient survival was underestimated using KM versus CRA methods in patients with pancreas and kidney graft losses (25.4% vs. 36.2%), respectively. Induction with lymphocyte depleting antibodies was associated with 81% reduced risk (HR.19, 95% CI.38-.98, p = .0048), while delayed kidney function (HR 2.94, 95% CI 1.09-7.95, p = .033) and surgical complications (HR 2.94, 95% CI 1.22-7.08, p = .016) were associated with higher risk of death. Four-year patient survival increased from Era 1 to Era 5 (79% vs. 87.9%, p = .047). CONCLUSION In this cohort of patients, kidney graft loss, with or without pancreas graft loss, was associated with higher mortality after SPK transplantation. Compared to CRA, the KM model underestimated survival only among patients with pancreas and kidney graft losses. Patient survival increased over time.
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Affiliation(s)
| | | | - Érika Bevilaqua Rangel
- Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Luis Gustavo Modelli
- Division of Nephrology, Department of Internal Medicine, Universidade Estadual Paulista (UNESP), Botucatu, Brazil
| | | | | | - Lúcio Requião-Moura
- Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil
| | | | - Helio Tedesco-Silva
- Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil
| | - José Medina Pestana
- Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil
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Grasberger J, Ortiz F, Ekstrand A, Sallinen V, Ahopelto K, Finne P, Gissler M, Lempinen M, Helanterä I. Infection-Related Hospitalizations After Simultaneous Pancreas-Kidney Transplantation Compared to Kidney Transplantation Alone. Transpl Int 2024; 37:12235. [PMID: 38444997 PMCID: PMC10912468 DOI: 10.3389/ti.2024.12235] [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: 10/14/2023] [Accepted: 02/06/2024] [Indexed: 03/07/2024]
Abstract
The total burden of infections after transplantation has not been compared in detail between recipients of simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). We compared infection-related hospitalizations and bacteremias after transplantation during 1- and 5-year follow-up among 162 patients undergoing SPK. The control group consisted of 153 type 1 diabetics undergoing KTA with the inclusion criteria of donor and recipient age < 60, and BMI < 30. During the first year, SPK patients had more infection-related hospitalizations (0.54 vs. 0.31 PPY, IRR 1.76, p = <0.001) and bacteremias (0.11 vs. 0.01 PPY, IRR 17.12, p = <0.001) compared to KTA patients. The first infection-related hospitalizations and bacteremias occurred later during follow-up in KTA patients. SPK was an independent risk factor for infection-related hospitalization and bacteremia during the first year after transplantation, but not during the 5-year follow-up. Patient survival did not differ between groups, however, KTA patients had inferior kidney graft survival. SPK patients are at greater risk for infection-related hospitalizations and bacteremias during the first year after transplantation compared to KTA patients, however, at the end of the follow-up the risk of infection was similar between groups.
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Affiliation(s)
- Juulia Grasberger
- Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Fernanda Ortiz
- Nephrology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Agneta Ekstrand
- Nephrology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Ville Sallinen
- Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Kaisa Ahopelto
- Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Patrik Finne
- Nephrology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Mika Gissler
- Department of Knowledge Brokers, Finnish Institute for Health and Welfare, Helsinki, Finland
- Academic Primary Health Care Centre, Region Stockholm, Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Marko Lempinen
- Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Ilkka Helanterä
- Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
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Caldara R, Tomajer V, Monti P, Sordi V, Citro A, Chimienti R, Gremizzi C, Catarinella D, Tentori S, Paloschi V, Melzi R, Mercalli A, Nano R, Magistretti P, Partelli S, Piemonti L. Allo Beta Cell transplantation: specific features, unanswered questions, and immunological challenge. Front Immunol 2023; 14:1323439. [PMID: 38077372 PMCID: PMC10701551 DOI: 10.3389/fimmu.2023.1323439] [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: 10/17/2023] [Accepted: 11/06/2023] [Indexed: 12/18/2023] Open
Abstract
Type 1 diabetes (T1D) presents a persistent medical challenge, demanding innovative strategies for sustained glycemic control and enhanced patient well-being. Beta cells are specialized cells in the pancreas that produce insulin, a hormone that regulates blood sugar levels. When beta cells are damaged or destroyed, insulin production decreases, which leads to T1D. Allo Beta Cell Transplantation has emerged as a promising therapeutic avenue, with the goal of reinstating glucose regulation and insulin production in T1D patients. However, the path to success in this approach is fraught with complex immunological hurdles that demand rigorous exploration and resolution for enduring therapeutic efficacy. This exploration focuses on the distinct immunological characteristics inherent to Allo Beta Cell Transplantation. An understanding of these unique challenges is pivotal for the development of effective therapeutic interventions. The critical role of glucose regulation and insulin in immune activation is emphasized, with an emphasis on the intricate interplay between beta cells and immune cells. The transplantation site, particularly the liver, is examined in depth, highlighting its relevance in the context of complex immunological issues. Scrutiny extends to recipient and donor matching, including the utilization of multiple islet donors, while also considering the potential risk of autoimmune recurrence. Moreover, unanswered questions and persistent gaps in knowledge within the field are identified. These include the absence of robust evidence supporting immunosuppression treatments, the need for reliable methods to assess rejection and treatment protocols, the lack of validated biomarkers for monitoring beta cell loss, and the imperative need for improved beta cell imaging techniques. In addition, attention is drawn to emerging directions and transformative strategies in the field. This encompasses alternative immunosuppressive regimens and calcineurin-free immunoprotocols, as well as a reevaluation of induction therapy and recipient preconditioning methods. Innovative approaches targeting autoimmune recurrence, such as CAR Tregs and TCR Tregs, are explored, along with the potential of stem stealth cells, tissue engineering, and encapsulation to overcome the risk of graft rejection. In summary, this review provides a comprehensive overview of the inherent immunological obstacles associated with Allo Beta Cell Transplantation. It offers valuable insights into emerging strategies and directions that hold great promise for advancing the field and ultimately improving outcomes for individuals living with diabetes.
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Affiliation(s)
- Rossana Caldara
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Valentina Tomajer
- Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Paolo Monti
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Valeria Sordi
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Antonio Citro
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Raniero Chimienti
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
- Università Vita-Salute San Raffaele, Milan, Italy
| | - Chiara Gremizzi
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Davide Catarinella
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Stefano Tentori
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Vera Paloschi
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Raffella Melzi
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Alessia Mercalli
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Rita Nano
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Paola Magistretti
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Stefano Partelli
- Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
- Università Vita-Salute San Raffaele, Milan, Italy
| | - Lorenzo Piemonti
- Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
- Università Vita-Salute San Raffaele, Milan, Italy
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Giuliani T, Ibáñez JM, Orón EM, Robledo AB, Chicote CM, Hernando Sanz A, Ballester Ibáñez C, Mizrahi DC, Castelló IB, Merino Torres JF, López Andújar R. Appraising pancreatic fistula in pancreas transplantation: A comprehensive complication index based analysis of postoperative outcomes and predictors of graft survival. Pancreatology 2022; 22:1167-1174. [PMID: 36220755 DOI: 10.1016/j.pan.2022.09.238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/05/2022] [Accepted: 09/12/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND A definition of pancreatic fistula specifically addressing pancreas transplantation (PT) is lacking. This study sought to characterize pancreatic fistula in this setting and to define its clinical relevance on the postoperative course and long-term graft survival (GS). METHODS Consecutive simultaneous pancreas and kidney transplantations were analysed. The global postoperative course was assessed through the comprehensive complication index (CCI). PF was defined according to the original International Study Group for Pancreatic Surgery (ISGPS) definition. Predictors of poor postoperative course and GS were explored. RESULTS Seventy-eight patients were analysed. Surgical morbidity was 48.7%, with severe complications occurring in 39.7%. Ninety-day mortality was 2.6%. PF occurred in 56.6% of patients, although its average clinical burden was low and did not correlate with either early or long-term outcomes. Peri-graft fluid collections, postoperative day (POD) 1 drain fluid amylase (DFA) ≥ 2200 U/L, and POD 5 DFA/serum amylase ratio ≥7.0 independently correlated with poor postoperative course. Perigraft fluid collections were associated with reduced GS. CONCLUSION Conventionally defined pancreatic fistula is frequent following PT, although its clinical impact is negligible. To define clinically relevant PF, novel cut-offs for DFA might be pondered in a future series, while perigraft fluid collections should be strongly considered.
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Affiliation(s)
- Tommaso Giuliani
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain; Department of General and Pancreatic Surgery, Verona Hospital Trust, University of Verona, Verona, Italy
| | - Javier Maupoey Ibáñez
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Eva Montalvá Orón
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Andrea Boscà Robledo
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Cristina Martínez Chicote
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Ana Hernando Sanz
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Cristina Ballester Ibáñez
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - David Calatayud Mizrahi
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Isabel Beneyto Castelló
- Department of Nephrology and Kidney Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | | | - Rafael López Andújar
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain.
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6
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Favorable Outcomes in Older Recipients Receiving Simultaneous Pancreas Kidney Transplantation. Transplant Direct 2022; 8:e1413. [PMCID: PMC9671747 DOI: 10.1097/txd.0000000000001413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/21/2022] [Accepted: 09/22/2022] [Indexed: 11/19/2022] Open
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Ji M, Wang M, Hu W, Ibrahim M, Lentine KL, Merzkani M, Murad H, Al-Hosni Y, Parsons R, Wellen J, Chang SH, Alhamad T. Survival After Simultaneous Pancreas‐Kidney Transplantation in Type 1 Diabetes: The Critical Role of Early Pancreas Allograft Function. Transpl Int 2022; 35:10618. [PMID: 36171743 PMCID: PMC9510367 DOI: 10.3389/ti.2022.10618] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 08/24/2022] [Indexed: 11/28/2022]
Abstract
Simultaneous pancreas-kidney transplantation (SPK) carries about a 7%–22% risk of technical failure, but the impact of early pancreas allograft loss on subsequent kidney graft and patient survival is not well-defined. We examined national transplant registry data for type 1 diabetic patients who received SPK between 2000 and 2021. Associations of transplant type (i.e., SPK, deceased‐donor kidney transplant [DDKA], living‐donor kidney transplant [LDKA]) with kidney graft failure and patient survival were estimated by multivariable inverse probability of treatment-weighted accelerated failure-time models. Compared to SPK recipients with a functioning pancreas graft 3 months posttransplant (SPK,P+), LDKA had 18% (Time Ratio [TR] 0.82, 95%CI: 0.70–0.95) less graft survival time and 18% (TR 0.82, 95%CI: 0.68–0.97) less patient survival time, DDKA had 23% (TR 0.77, 95%CI: 0.68–0.87) less graft survival time and 29% (TR 0.71, 95%CI: 0.62–0.81) less patient survival time, and SPK with early pancreas graft loss had 34% (TR 0.66, 95%CI: 0.56–0.78) less graft survival time and 34% (TR 0.66, 95%CI: 0.55–0.79) less patient survival time. In conclusion, SPK,P+ recipients have better kidney allograft and patient survival compared with LDKA and DDKA. Early pancreas graft failure results in inferior kidney and patient survival time compared to kidney transplant alone.
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Affiliation(s)
- Mengmeng Ji
- School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
| | - Mei Wang
- School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
| | - Wenjun Hu
- School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
| | - Mohamed Ibrahim
- School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
| | - Krista L. Lentine
- Division of Nephrology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO, United States
| | - Massini Merzkani
- School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
| | - Haris Murad
- School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
| | - Yazen Al-Hosni
- School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
| | - Ronald Parsons
- Division of Transplantation, Department of Surgery, Emory University School of Medicine, Atlanta, GA, United States
| | - Jason Wellen
- School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
| | - Su-Hsin Chang
- School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
| | - Tarek Alhamad
- School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
- *Correspondence: Tarek Alhamad,
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Jiang S, Xu CM, Yao S, Zhang R, Li XZ, Zhang RZ, Xie TY, Xing YQ, Zhang Q, Zhou XJ, Liao L, Dong JJ. Cdc42 upregulation under high glucose induces podocyte apoptosis and impairs β-cell insulin secretion. Front Endocrinol (Lausanne) 2022; 13:905703. [PMID: 36034435 PMCID: PMC9399854 DOI: 10.3389/fendo.2022.905703] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 07/15/2022] [Indexed: 01/19/2023] Open
Abstract
OBJECTIVES The progressive impairment of β-cell function results in prolonged deterioration in patients with type 2 diabetes mellitus (T2DM). Interestingly, the finding on pancreatitis secondary to renal injury suggests that potential communication exists between kidney and pancreas. Therefore, we aimed to investigate cell division cycle 42 (Cdc42)-mediated podocyte apoptosis and its effect on insulin secretion in islet β-cells. METHODS Type 2 diabetic nephropathy mouse models were established to identify the expression of Cdc42 in podocytes by immunohistochemistry. An in vitro co-culture of mouse podocyte MPC5 and β-TC6 cells was preliminarily established. Subsequently, podocyte apoptosis induced by high glucose and Cdc42 was detected by TUNEL staining and western blotting. In addition, the JNK pathway was examined to determine the mechanism of apoptosis in MPC5 cells. Finally, insulin secretion and expression in β-TC6 cells as well as malondialdehyde (MDA) and superoxide dismutase (SOD) levels in both cell types were examined after the regulation of Cdc42 in MPC5 cells. RESULTS Cdc42 was highly expressed in the podocytes of diabetic nephropathy mice. Exposure to 25 mM glucose for 48 h induced a significant upregulation of Cdc42, Bax, and cleaved caspase-3 as well as a decreased Bcl-2 expression. In addition, marked apoptosis of MPC5 cells was observed compared to normal glucose treatment. After transfection with Cdc42 plasmid, apoptosis of MPC5 cells was enhanced with an increased expression of p-JNK, whereas inhibition of Cdc42 significantly alleviated podocyte apoptosis accompanied by a downregulation of p-JNK. The glucose-stimulated insulin secretion level of β-TC6 cells decreased after the upregulation of Cdc42 in MPC5 cells. Immunofluorescence staining for insulin showed that co-culture with MPC5 cells carrying the Cdc42 plasmid significantly reduced insulin expression, whereas inhibition of Cdc42 in MPC5 cells alleviated the above-mentioned abnormality of β-TC6 cells. The expression of Cdc42 and p-p38 in β-TC6 cells increased following the upregulation of Cdc42 in MPC5 cells; this was concurrent with augmented MDA levels and decreased SOD activity. The opposite result was observed for Cdc42 knockdown in MPC5 cells. CONCLUSIONS Cdc42 in podocytes plays a crucial role in insulin secretion by β-cells, which may provide a new therapeutic target to prevent the vicious cycle of β-cell dysfunction in T2DM.
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Affiliation(s)
- Shan Jiang
- Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Chun-mei Xu
- Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China
| | - Shuai Yao
- Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Rui Zhang
- Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xian-zhi Li
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qian Foshan Hospital, Shandong Institute of Nephrology, Jinan, China
- Department of Endocrinology and Metabology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Ru-zhen Zhang
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qian Foshan Hospital, Shandong Institute of Nephrology, Jinan, China
- Department of Endocrinology and Metabology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Tian-yue Xie
- Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yi-qian Xing
- Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Qian Zhang
- Department of Pharmacology, Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, Jinan, China
| | - Xiao-jun Zhou
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qian Foshan Hospital, Shandong Institute of Nephrology, Jinan, China
- Department of Endocrinology and Metabology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- *Correspondence: Lin Liao, ; Jian-jun Dong, ; Xiao-jun Zhou,
| | - Lin Liao
- Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qian Foshan Hospital, Shandong Institute of Nephrology, Jinan, China
- *Correspondence: Lin Liao, ; Jian-jun Dong, ; Xiao-jun Zhou,
| | - Jian-jun Dong
- Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- *Correspondence: Lin Liao, ; Jian-jun Dong, ; Xiao-jun Zhou,
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9
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Piemonti L. Felix dies natalis, insulin… ceterum autem censeo "beta is better". Acta Diabetol 2021; 58:1287-1306. [PMID: 34027619 DOI: 10.1007/s00592-021-01737-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 05/06/2021] [Indexed: 12/12/2022]
Abstract
One hundred years after its discovery, insulin remains the life-saving therapy for many patients with diabetes. It has been a 100-years-old success story thanks to the fact that insulin therapy has continuously integrated the knowledge developed over a century. In 1982, insulin becomes the first therapeutic protein to be produced using recombinant DNA technology. The first "mini" insulin pump and the first insulin pen become available in 1983 and 1985, respectively. In 1996, the first generation of insulin analogues were produced. In 1999, the first continuous glucose-monitoring device for reading interstitial glucose was approved by the FDA. In 2010s, the ultra-long action insulins were introduced. An equally exciting story developed in parallel. In 1966. Kelly et al. performed the first clinical pancreas transplant at the University of Minnesota, and now it is a well-established clinical option. First successful islet transplantations in humans were obtained in the late 1980s and 1990s. Their ability to consistently re-establish the endogenous insulin secretion was obtained in 2000s. More recently, the possibility to generate large numbers of functional human β cells from pluripotent stem cells was demonstrated, and the first clinical trial using stem cell-derived insulin producing cell was started in 2014. This year, the discovery of this life-saving hormone turns 100 years. This provides a unique opportunity not only to celebrate this extraordinary success story, but also to reflect on the limits of insulin therapy and renew the commitment of the scientific community to an insulin free world for our patients.
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Affiliation(s)
- Lorenzo Piemonti
- San Raffaele Diabetes Research Institute, San Raffaele Scientific Institute, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
- Università Vita-Salute San Raffaele, Milan, Italy.
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10
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Boggi U, Vistoli F, Andres A, Arbogast HP, Badet L, Baronti W, Bartlett ST, Benedetti E, Branchereau J, Burke GW, Buron F, Caldara R, Cardillo M, Casanova D, Cipriani F, Cooper M, Cupisti A, Davide J, Drachenberg C, de Koning EJP, Ettorre GM, Fernandez Cruz L, Fridell JA, Friend PJ, Furian L, Gaber OA, Gruessner AC, Gruessner RW, Gunton JE, Han D, Iacopi S, Kauffmann EF, Kaufman D, Kenmochi T, Khambalia HA, Lai Q, Langer RM, Maffi P, Marselli L, Menichetti F, Miccoli M, Mittal S, Morelon E, Napoli N, Neri F, Oberholzer J, Odorico JS, Öllinger R, Oniscu G, Orlando G, Ortenzi M, Perosa M, Perrone VG, Pleass H, Redfield RR, Ricci C, Rigotti P, Paul Robertson R, Ross LF, Rossi M, Saudek F, Scalea JR, Schenker P, Secchi A, Socci C, Sousa Silva D, Squifflet JP, Stock PG, Stratta RJ, Terrenzio C, Uva P, Watson CJ, White SA, Marchetti P, Kandaswamy R, Berney T. First World Consensus Conference on pancreas transplantation: Part II - recommendations. Am J Transplant 2021; 21 Suppl 3:17-59. [PMID: 34245223 PMCID: PMC8518376 DOI: 10.1111/ajt.16750] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 06/25/2021] [Accepted: 06/26/2021] [Indexed: 02/07/2023]
Abstract
The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.
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11
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Lonze BE, Baptiste G, Ali NM, Dagher NN, Gelb BE, Mattoo A, Soomro I, Tatapudi VS, Montgomery RA, Stewart ZA. Pancreas transplantation from hepatitis C viremic donors to uninfected recipients. Am J Transplant 2021; 21:1931-1936. [PMID: 33346951 DOI: 10.1111/ajt.16465] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 12/13/2020] [Accepted: 12/15/2020] [Indexed: 01/25/2023]
Abstract
Despite utilization of hepatitis C viremic organs for hepatitis C naïve recipients (HCV D+/R-) in other solid organ transplants, HCV viremic pancreata remain an unexplored source of donor organs. This study reports the first series of HCV D+/R- pancreas transplants. HCV D+/R- had shorter waitlist times compared to HCV D-/R-, waiting a mean of 16 days from listing for HCV-positive organs. HCV D+/R- had a lower match allocation sequence than HCV D-/R-, and this correlated with receipt of organs with a lower Pancreas Donor Risk Index (PDRI) score. All HCV D+/R- had excellent graft function with a mean follow-up of 438 days and had undetectable HCV RNA levels by a mean of 23 days after initiation of HCV-directed therapy. The rates of infectious complications, reoperation, readmission, rejection, and length of stay were not impacted by donor HCV status. A national review of potential ideal pancreas donors found that 37% of ideal HCV-negative pancreas allografts were transplanted, compared to only 5% of ideal HCV-positive pancreas allografts. The results of the current study demonstrate the safety of accepting HCV-positive pancreata for HCV-naïve recipients and advocates for increased utilization of ideal HCV-positive pancreas allografts.
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Affiliation(s)
- Bonnie E Lonze
- Transplant Institute, NYU Langone Health, New York, New York, USA
| | - Gillian Baptiste
- Department of Surgery, NYU Langone Health, New York, New York, USA
| | - Nicole M Ali
- Transplant Institute, NYU Langone Health, New York, New York, USA
| | - Nabil N Dagher
- Transplant Institute, NYU Langone Health, New York, New York, USA
| | - Bruce E Gelb
- Transplant Institute, NYU Langone Health, New York, New York, USA
| | - Aprajita Mattoo
- Transplant Institute, NYU Langone Health, New York, New York, USA
| | - Irfana Soomro
- Transplant Institute, NYU Langone Health, New York, New York, USA
| | | | | | - Zoe A Stewart
- Transplant Institute, NYU Langone Health, New York, New York, USA
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12
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Wong WS, McKay G, Stevens KI. Diabetic kidney disease and transplantation options. PRACTICAL DIABETES 2021. [DOI: 10.1002/pdi.2330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Affiliation(s)
- Wan S Wong
- Renal and Transplant Unit Queen Elizabeth University Hospital Glasgow UK
| | - Gerard McKay
- Department of Diabetes, Endocrinology and Clinical Pharmacology, Glasgow Royal Infirmary Glasgow UK
| | - Kathryn I Stevens
- Renal and Transplant Unit Queen Elizabeth University Hospital Glasgow UK
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13
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Messner F, Leemkuil M, Yu Y, Massie AB, Krendl FJ, Benjamens S, Bösmüller C, Weissenbacher A, Schneeberger S, Pol RA, Margreiter C. Recipient age and outcome after pancreas transplantation: a retrospective dual-center analysis. Transpl Int 2021; 34:657-668. [PMID: 33570795 PMCID: PMC8049064 DOI: 10.1111/tri.13845] [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: 07/15/2020] [Revised: 08/24/2020] [Accepted: 02/08/2021] [Indexed: 01/16/2023]
Abstract
With a later onset of diabetes complications and thus increasing age of transplant candidates, many centers have extended upper age limits for pancreas transplantation. This study investigates the effect of recipient and donor age on outcomes after pancreas transplantation.We retrospectively analyzed 565 pancreas transplants performed at two Eurotransplant centers. The cohort was split at a recipient and donor age of 50 and 40 years, respectively. Median recipient age in old patients (≥50 years; 27.2%) was 54 years and 40 years in young patients (<50 years). Compared to young recipients, old recipients had an inferior patient survival rate (≥50: 5yr, 82.8%; 10yr, 65.6%; <50: 5yr, 93.3%; 10yr, 82.0%; P < 0.0001). Old recipients demonstrated comparable death-censored pancreas (≥50: 1yr, 80.6%; 5yr, 70.2%; <50: 1yr, 87.3%; 5yr, 77.8%; P = 0.35) and kidney graft survival (≥50: 1yr, 97.4%; 5yr, 90.6%; <50: 1yr, 97.8%; 5yr, 90.2%; P = 0.53) compared to young recipients. Besides a lower rate of kidney rejection, similar relative risks for postoperative complications were detected in old and young patients. This study shows that despite an increased mortality in old recipients, excellent graft survival can be achieved similar to that of young patients. Age alone should not exclude patients from receiving a pancreas transplant.
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Affiliation(s)
- Franka Messner
- Department of Visceral, Transplant and Thoracic SurgeryCenter of Operative MedicineMedical University of InnsbruckInnsbruckAustria
| | - Marjolein Leemkuil
- Department of SurgeryUniversity Medical Center GroningenGroningenThe Netherlands
| | - Yifan Yu
- Department of EpidemiologyJohns Hopkins School of Public HealthBaltimoreMDUSA
| | - Allan B. Massie
- Department of EpidemiologyJohns Hopkins School of Public HealthBaltimoreMDUSA
- Department of SurgeryJohns Hopkins University School of MedicineBaltimoreMDUSA
| | - Felix J. Krendl
- Department of Visceral, Transplant and Thoracic SurgeryCenter of Operative MedicineMedical University of InnsbruckInnsbruckAustria
| | - Stan Benjamens
- Department of SurgeryUniversity Medical Center GroningenGroningenThe Netherlands
| | - Claudia Bösmüller
- Department of Visceral, Transplant and Thoracic SurgeryCenter of Operative MedicineMedical University of InnsbruckInnsbruckAustria
| | - Annemarie Weissenbacher
- Department of Visceral, Transplant and Thoracic SurgeryCenter of Operative MedicineMedical University of InnsbruckInnsbruckAustria
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thoracic SurgeryCenter of Operative MedicineMedical University of InnsbruckInnsbruckAustria
| | - Robert A. Pol
- Department of SurgeryUniversity Medical Center GroningenGroningenThe Netherlands
| | - Christian Margreiter
- Department of Visceral, Transplant and Thoracic SurgeryCenter of Operative MedicineMedical University of InnsbruckInnsbruckAustria
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14
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Impact of Simultaneous Pancreas-kidney Transplantation on Cardiovascular Risk in Patients With Diabetes. Transplantation 2021; 106:158-166. [PMID: 33660656 DOI: 10.1097/tp.0000000000003710] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND cardiovascular disease is the major cause of death in patients with type 1 Diabetes. Of the available risk predictors for this population, the Steno Type 1 Risk Engine (STENO T1) is the only one which includes kidney function as a risk factor, which is a well described independent risk factor for cardiovascular disease. METHODS we explore how SPKT modifies the predicted cardiovascular risk by the STENO T1 through a retrospective study including recipients of a first SPKT between 2000 and 2016. RESULTS 268 SPKT recipients with a mean age of 40 years old and a median follow-up of 10 years were included. Prior to transplantation, the expected incidence of Cardiovascular Events (CVE) at 5 and 10 years according to STENO T1 would have been 31% and 50%, respectively, contrasting with an actual incidence of 9.3% and 16% for the same timepoints, respectively (P < 0.05). These differences were attenuated when STENO T1 was recalculated assuming 12th month glomerular filtration rate (at 5 and 10 years predicted CVE incidence was of 10.5% and 19.4%, respectively). Early pancreas graft failure (HR 3.00 [95% CI 1.14 - 7.88]; P = 0.02) was an independent risk factor for post-SPKT CVE, alongside with kidney graft failure (HR 2.90 [95% CI 1.53 - 5.48]; P = 0.001), and diabetes duration (HR 1.04 [95% CI 1.00-1.09], P = 0.04). CONCLUSIONS SPKT decreases in more two-thirds the predicted cardiovascular risk by the STENO T1. A functioning pancreas graft further reduces CVE risk, independently of kidney graft function.
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15
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Perdue JM, Ortiz AC, Parsikia A, Ortiz J. Kidney-Pancreas Transplant Recipients Experience Higher Risk of Complications Compared to the General Population after Undergoing Coronary Artery Bypass Grafting. Int J Angiol 2021; 30:107-116. [PMID: 34054268 DOI: 10.1055/s-0040-1721680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
This retrospective analysis aims to identify differences in surgical outcomes between pancreas and/or kidney transplant recipients compared with the general population undergoing coronary artery bypass grafting (CABG). Using Nationwide Inpatient Sample (NIS) data from 2005 to 2014, patients who underwent CABG were stratified by either no history of transplant, or history of pancreas and/or kidney transplant. Multivariate analysis was used to calculate odds ratio (OR) to evaluate in-hospital mortality, morbidity, length of stay (LOS), and total hospital charge in all centers. The analysis was performed for both nonemergency and emergency CABG. Overall, 2,678 KTx (kidney transplant alone), 184 PTx (pancreas transplant alone), 254 KPTx (kidney-pancreas transplant recipients), and 1,796,186 Non-Tx (nontransplant) met inclusion criteria. KPTx experienced higher complication rates compared with Non-Tx (78.3 vs. 47.8%, p < 0.01). Those with PTx incurred greater total hospital charge and LOS. On weighted multivariate analysis, KPTx was associated with an increased risk for developing any complication following CABG (OR 3.512, p < 0.01) and emergency CABG (3.707, p < 0.01). This risk was even higher at transplant centers (CABG OR 4.302, p < 0.01; emergency CABG OR 10.072, p < 0.001). KTx was associated with increased in-hospital mortality following emergency CABG, while PTx and KPTx had no mortality to analyze. KPTx experienced a significantly higher risk of complications compared with the general population after undergoing CABG, in both transplant and nontransplant centers. These outcomes should be considered when providing perioperative care.
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Affiliation(s)
- Jordyn M Perdue
- Department of Surgery, University of Toledo College of Medicine, Toledo, Ohio
| | | | - Afshin Parsikia
- Department of Surgery, University of Toledo College of Medicine, Toledo, Ohio
| | - Jorge Ortiz
- Department of Surgery, University of Toledo College of Medicine, Toledo, Ohio
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16
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Das DM, Huskey JL, Harbell JW, Heilman RL, Singer AL, Mathur A, Neville MR, Morgan P, Reddy KS, Jadlowiec CC. Early technical pancreas failure in Simultaneous Pancreas-Kidney Recipients does not impact renal allograft outcomes. Clin Transplant 2020; 35:e14138. [PMID: 33131111 DOI: 10.1111/ctr.14138] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 10/12/2020] [Accepted: 10/19/2020] [Indexed: 01/08/2023]
Abstract
Early pancreas loss in simultaneous pancreas-kidney (SPK) transplants has been associated with longer perioperative recovery and reduced kidney allograft function. We assessed the impact of early pancreas allograft failure on transplant outcomes in a contemporary cohort of SPK patients (n = 218). Early pancreas allograft loss occurred in 12.8% (n = 28) of recipients. Delayed graft function (DGF) was more common (21.4% vs. 7.4%, p = 0.03) in the early pancreas loss group, but there were no differences in hospital length of stay (median 6.5 vs. 7.0, p = 0.22), surgical wound complications (p = 0.12), or rejection episodes occurring in the first year (p = 0.87). Despite differences in DGF, both groups had excellent renal function at 1 year post-transplant (eGFR 64.1 ± 20.8 vs. 65.8 ± 22.9, p = 0.75). There were no differences in patient (HR 0.58, 95% CI 0.18-1.87, p = 0.26) or kidney allograft survival (HR 0.84, 95% CI 0.23-3.06, p = 0.77). One- and 2-year protocol kidney biopsies were comparable between the groups and showed minimal chronic changes; the early pancreas loss group showed more cv changes at 2 years (p = 0.04). Current data demonstrate good outcomes and excellent kidney allograft function following early pancreas loss.
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Affiliation(s)
- Devika M Das
- Mayo Clinic Alix School of Medicine, Scottsdale, AZ, USA
| | | | - Jack W Harbell
- Division of Transplant Surgery, Mayo Clinic, Phoenix, AZ, USA
| | | | - Andrew L Singer
- Division of Transplant Surgery, Mayo Clinic, Phoenix, AZ, USA
| | - Amit Mathur
- Division of Transplant Surgery, Mayo Clinic, Phoenix, AZ, USA
| | - Matthew R Neville
- Instructor in Biostatistics, Mayo Clinic College of Medicine, Phoenix, AZ, USA
| | - Paige Morgan
- Division of Transplant Surgery, Mayo Clinic, Phoenix, AZ, USA
| | - Kunam S Reddy
- Division of Transplant Surgery, Mayo Clinic, Phoenix, AZ, USA
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17
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Shingde R, Calisa V, Craig JC, Chapman JR, Webster AC, Pleass H, O’Connell PJ, Allen R, Robertson P, Yuen L, Kable K, Nankivell B, Rogers NM, Wong G. Relative survival and quality of life benefits of pancreas–kidney transplantation, deceased kidney transplantation and dialysis in type 1 diabetes mellitus—a probabilistic simulation model. Transpl Int 2020; 33:1393-1404. [DOI: 10.1111/tri.13679] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 04/27/2020] [Accepted: 06/17/2020] [Indexed: 12/16/2022]
Affiliation(s)
- Rashmi Shingde
- Renal Unit Westmead Hospital Westmead NSW Australia
- Centre for Kidney Research Kids Research InstituteThe Children’s Hospital at Westmead Westmead NSW Australia
| | - Vaishnavi Calisa
- Renal Unit Westmead Hospital Westmead NSW Australia
- Centre for Kidney Research Kids Research InstituteThe Children’s Hospital at Westmead Westmead NSW Australia
| | - Jonathan C. Craig
- College of Medicine and Public Health Flinders University Adelaide SA Australia
| | - Jeremy R. Chapman
- Centre for Transplant and Renal Research Westmead Institute for Medical Research Westmead NSW Australia
| | - Angela C. Webster
- Centre for Kidney Research Kids Research InstituteThe Children’s Hospital at Westmead Westmead NSW Australia
- Sydney School of Public Health University of Sydney Sydney NSW Australia
| | - Henry Pleass
- Centre for Transplant and Renal Research Westmead Institute for Medical Research Westmead NSW Australia
- Department of Surgery Westmead Hospital Westmead NSW Australia
| | - Philip J. O’Connell
- Renal Unit Westmead Hospital Westmead NSW Australia
- Centre for Transplant and Renal Research Westmead Institute for Medical Research Westmead NSW Australia
| | - Richard Allen
- Centre for Transplant and Renal Research Westmead Institute for Medical Research Westmead NSW Australia
- Department of Surgery Westmead Hospital Westmead NSW Australia
| | - Paul Robertson
- Centre for Transplant and Renal Research Westmead Institute for Medical Research Westmead NSW Australia
| | - Lawrence Yuen
- Centre for Transplant and Renal Research Westmead Institute for Medical Research Westmead NSW Australia
- Department of Surgery Westmead Hospital Westmead NSW Australia
| | - Kathy Kable
- Centre for Transplant and Renal Research Westmead Institute for Medical Research Westmead NSW Australia
| | - Brian Nankivell
- Centre for Transplant and Renal Research Westmead Institute for Medical Research Westmead NSW Australia
| | - Natasha M. Rogers
- Renal Unit Westmead Hospital Westmead NSW Australia
- Centre for Transplant and Renal Research Westmead Institute for Medical Research Westmead NSW Australia
| | - Germaine Wong
- Renal Unit Westmead Hospital Westmead NSW Australia
- Centre for Kidney Research Kids Research InstituteThe Children’s Hospital at Westmead Westmead NSW Australia
- College of Medicine and Public Health Flinders University Adelaide SA Australia
- Centre for Transplant and Renal Research Westmead Institute for Medical Research Westmead NSW Australia
- Sydney School of Public Health University of Sydney Sydney NSW Australia
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18
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Ito T, Kenmochi T, Aida N, Matsushima H, Kurihara K, Ishihara T, Shintani A, Asaoka T, Ito T. Impact of Pancreas Transplantation on the Patient Survival-An Analysis of the Japanese Pancreas Transplants Registry. J Clin Med 2020; 9:jcm9072134. [PMID: 32640735 PMCID: PMC7408615 DOI: 10.3390/jcm9072134] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/27/2020] [Accepted: 06/29/2020] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND The impact of pancreas transplantation, including kidney transplantation on patients' life prognoses, is unclear in Japan. An analysis of the data of the Japan Pancreas Transplant Registry was performed to compare the patient survival between on the waiting list and after pancreas transplantation, and investigate the factors that affect the patient survival after pancreatic transplantation. METHODS The life prognoses of 361 patients who underwent pancreas transplantation from 2000 to December 2018 were examined. RESULTS The survival rates at 1, 5, and 10 years on the waiting list were 98.4%, 90.3%, and 78.1%, respectively, while those after transplantation were significantly improved (p = 0.029) at 100%, 97.5%, and 88.9%, respectively. Furthermore, the survival rates of patients waiting for simultaneous pancreas and kidney transplantation (SPK) at 1, 5, and 10 years were 98.2%, 89.4%, and 75.4%, respectively, while those after SPK were also significantly improved (p = 0.026) at 100%, 94.6%, and 88.8%. The multivariable analysis revealed that the duration of diabetes before surgery was the only independent risk factor (hazard ratio = 1.095, p = 0.012) that affected the patient survival after SPK. CONCLUSION Pancreas transplantation was found to improve the life prognosis of patients with type 1 diabetes, especially those with end-stage renal failure waiting for SPK.
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Affiliation(s)
- Taihei Ito
- Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University, Dengakugakubo 1-98, Kutsukakecho, Toyoake-shi, Aichi 470-1192, Japan; (T.K.); (N.A.); (H.M.); (K.K.)
- Correspondence: ; Tel.: +5-62-93-2000; Fax: +5-62-93-7060
| | - Takashi Kenmochi
- Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University, Dengakugakubo 1-98, Kutsukakecho, Toyoake-shi, Aichi 470-1192, Japan; (T.K.); (N.A.); (H.M.); (K.K.)
| | - Naohiro Aida
- Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University, Dengakugakubo 1-98, Kutsukakecho, Toyoake-shi, Aichi 470-1192, Japan; (T.K.); (N.A.); (H.M.); (K.K.)
| | - Hajime Matsushima
- Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University, Dengakugakubo 1-98, Kutsukakecho, Toyoake-shi, Aichi 470-1192, Japan; (T.K.); (N.A.); (H.M.); (K.K.)
| | - Kei Kurihara
- Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University, Dengakugakubo 1-98, Kutsukakecho, Toyoake-shi, Aichi 470-1192, Japan; (T.K.); (N.A.); (H.M.); (K.K.)
| | - Takuma Ishihara
- Gifu University Hospital, Innovative and Clinical Research Promotion Center, Gifu University, Gifu 501-1193, Japan;
| | - Ayumi Shintani
- Department of Medical Statistics, Graduate School of Medicine, Osaka City University, Osaka 558-8585, Japan;
| | - Tadafumi Asaoka
- The Japan Pancreas Transplant Registry, Japan Society for Pancreas & Islet Transplantation, Osaka 565-0871, Japan; (T.A.); (T.I.)
| | - Toshinori Ito
- The Japan Pancreas Transplant Registry, Japan Society for Pancreas & Islet Transplantation, Osaka 565-0871, Japan; (T.A.); (T.I.)
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19
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Messner F, Yu Y, Etra JW, Krendl FJ, Berchtold V, Bösmüller C, Brandacher G, Oberhuber R, Scheidl S, Maglione M, Öfner D, Schneeberger S, Margreiter C. Donor cardiac arrest and cardiopulmonary resuscitation: impact on outcomes after simultaneous pancreas-kidney transplantation - a retrospective study. Transpl Int 2020; 33:657-666. [PMID: 32027055 PMCID: PMC7318239 DOI: 10.1111/tri.13591] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 12/12/2019] [Accepted: 02/03/2020] [Indexed: 01/16/2023]
Abstract
Donor cardiac arrest and cardiopulmonary resuscitation (CACPR) has been considered critically because of concerns over hypoperfusion and mechanical trauma to the donor organs. We retrospectively analyzed 371 first simultaneous pancreas–kidney transplants performed at the Medical University of Innsbruck between 1997 and 2017. We evaluated short‐ and long‐term outcomes from recipients of organs from donors with and without a history of CACPR. A total of 63 recipients received a pancreas and kidney graft from a CACPR donor. At 1, and 5‐years, patient survival was similar with 98.3%, and 96.5% in the CACPR and 97.0%, and 90.2% in the non‐CACPR group (log rank P = 0.652). Death‐censored pancreas graft survival was superior in the CACPR group with 98.3%, and 91.4% compared to 86.3%, and 77.4% (log rank P = 0.028) in the non‐CACPR group, which remained statistically significant even after adjustment [aHR 0.49 (95% CI 0.24–0.98), P = 0.044]. Similar relative risks for postoperative complications Clavien Dindo > 3a, pancreatitis, abscess, immunologic complications, delayed pancreas graft function, and relative length of stay were observed for both groups. Donors with a history of CACPR are, in the current practice, safe for transplantation. Stringent donor selection and short CPR durations may allow for outcomes surpassing those of donors without CACPR.
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Affiliation(s)
- Franka Messner
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Yifan Yu
- Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA
| | - Joanna W Etra
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Felix J Krendl
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Valeria Berchtold
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Claudia Bösmüller
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Gerald Brandacher
- Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA
| | - Rupert Oberhuber
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Scheidl
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Manuel Maglione
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Dietmar Öfner
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Christian Margreiter
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
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20
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Esmeijer K, Hoogeveen EK, van den Boog PJM, Konijn C, Mallat MJK, Baranski AG, Dekkers OM, de Fijter JW. Superior Long-term Survival for Simultaneous Pancreas-Kidney Transplantation as Renal Replacement Therapy: 30-Year Follow-up of a Nationwide Cohort. Diabetes Care 2020; 43:321-328. [PMID: 31801788 DOI: 10.2337/dc19-1580] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 11/03/2019] [Indexed: 02/03/2023]
Abstract
OBJECTIVE In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients. RESEARCH DESIGN AND METHODS We included all 2,796 patients with type 1 diabetes in the Netherlands who started renal replacement therapy between 1986 and 2016. We used multivariable Cox regression analyses adjusted for recipient age and sex, dialysis modality and vintage, transplantation era, and donor age to compare all-cause mortality between deceased- or living-donor kidney and SPK transplant recipients. Separately, we analyzed mortality between regions where SPK transplant was the preferred intervention (80% SPK) versus regions where a kidney transplant alone was favored (30% SPK). RESULTS Of 996 transplanted patients, 42%, 16%, and 42% received a deceased- or living-donor kidney or SPK transplant, respectively. Mean (SD) age at transplantation was 50 (11), 48 (11), and 42 (8) years, respectively. Median (95% CI) survival time was 7.3 (6.2; 8.3), 10.5 (7.2; 13.7), and 16.5 (15.1; 17.9) years, respectively. SPK recipients with a functioning pancreas graft at 1 year (91%) had the highest survival (median 17.4 years). Compared with deceased-donor kidney transplant recipients, adjusted hazard ratios (95% CI) for 10- and 20-year all-cause mortality were 0.79 (0.49; 1.29) and 0.98 (0.69; 1.39) for living-donor kidney and 0.67 (0.46; 0.98) and 0.79 (0.60; 1.05) for SPK recipients, respectively. A treatment strategy favoring SPK over kidney transplantation alone showed 10- and 20-year mortality hazard ratios of 0.56 (0.40; 0.78) and 0.69 (0.52; 0.90), respectively. CONCLUSIONS Compared with living- or deceased-donor kidney transplantation, SPK transplant was associated with improved patient survival, especially in recipients with a long-term functioning pancreatic graft, and resulted in an almost twofold lower 10-year mortality rate.
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Affiliation(s)
- Kevin Esmeijer
- Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
| | - Ellen K Hoogeveen
- Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.,Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | | | - Cynthia Konijn
- Netherlands Organ Transplantation Registry, Leiden, the Netherlands
| | - Marko J K Mallat
- Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
| | - Andre G Baranski
- Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | - Olaf M Dekkers
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.,Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
| | - Johan W de Fijter
- Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
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21
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Parajuli S, Arunachalam A, Swanson KJ, Aziz F, Garg N, Redfield RR, Kaufman D, Djamali A, Odorico J, Mandelbrot DA. Outcomes after simultaneous kidney-pancreas versus pancreas after kidney transplantation in the current era. Clin Transplant 2019; 33:e13732. [PMID: 31628870 DOI: 10.1111/ctr.13732] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 09/28/2019] [Accepted: 10/14/2019] [Indexed: 12/01/2022]
Abstract
Simultaneous pancreas and kidney (SPK) and pancreas after kidney (PAK) transplant are both potential options for diabetic ESRD patients. Historically, PAK pancreas graft outcomes were felt to be inferior to SPK pancreas graft outcomes. Little is known about outcomes in the modern era of transplantation. We analyzed our SPK and PAK recipients transplanted between 01/2000 and 12/2016. There were a total of 635 pancreas and kidney transplant recipients during the study period, 611 SPK and 24 PAK. Twelve of the PAK patients received a living donor kidney. There were no significant differences between the two groups in kidney or pancreas graft rejection at 1 year. Similarly, 1-year graft survival for both organs was not different. At last follow-up, uncensored and death-censored graft survival was not statistically different for kidney or pancreas grafts. In addition, in Cox regression analysis SPK and PAK were associated with similar graft survival. Although the majority of pancreas transplants are in the form of SPK, PAK is an acceptable alternative. Simultaneous pancreas and kidney avoids donor risks associated with live donation, so may be preferable in regions with short wait times, but PAK with a living donor kidney may be the best alternative in regions with long SPK wait times.
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Affiliation(s)
- Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Annamalai Arunachalam
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Kurtis J Swanson
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Fahad Aziz
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Neetika Garg
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Robert R Redfield
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Dixon Kaufman
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Arjang Djamali
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Jon Odorico
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Didier A Mandelbrot
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
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22
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Risk Indices in Deceased-donor Organ Allocation for Transplantation: Review From an Australian Perspective. Transplantation 2019; 103:875-889. [PMID: 30801513 DOI: 10.1097/tp.0000000000002613] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Over the last decade, organ donation and transplantation rates have increased in Australia and worldwide. Donor and recipient characteristics for most organ types have generally broadened, resulting in the need to consider more complex data in transplant decision-making. As a result of some of these pressures, the Australian software used for donor and recipient data management is currently being updated. Because of the in-built capacity for improved data management, organ allocation processes will have the opportunity to be significantly reviewed, in particular the possible use of risk indices (RIs) to guide organ allocation and transplantation decisions. We aimed to review RIs used in organ allocation policies worldwide and to compare their use to current Australian protocols. Significant donor, recipient, and transplant variables in the indices were summarized. We conclude that Australia has the opportunity to incorporate greater use of RIs in its allocation policies and in transplant decision-making processes. However, while RIs can assist with organ allocation and help guide prognosis, they often have significant limitations which need to be properly appreciated when deciding how to best use them to guide clinical decisions.
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23
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Aref A, Zayan T, Pararajasingam R, Sharma A, Halawa A. Pancreatic transplantation: Brief review of the current evidence. World J Transplant 2019; 9:81-93. [PMID: 31523630 PMCID: PMC6715578 DOI: 10.5500/wjt.v9.i4.81] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 07/15/2019] [Accepted: 07/30/2019] [Indexed: 02/05/2023] Open
Abstract
Kidney transplantation is the treatment of choice for management of end-stage renal disease. However, in diabetic patients, the underlying metabolic disturbance will persist and even may get worse after isolated kidney transplantation. Pancreatic transplantation in humans was first introduced in 1966. The initial outcome was disappointing. However, this was changed after the improvement of surgical techniques together with better patient selection and the availability of potent and better-tolerated immune-suppression like cyclosporine and induction antibodies. Combined kidney and pancreas transplantation will not only solve the problem of organ failure, but it will also stabilise or even reverse the metabolic complications of diabetes. Combined kidney and pancreas transplantation have the best long term outcome in diabetic cases with renal failure. Nevertheless, at the cost of an initial increase in morbidity and risk of mortality. Other transplantation options include pancreas after kidney transplantation and islet cell transplantation. We aim by this work to explore various options which can be offered to a diabetic patient with advanced chronic kidney disease. Our work will provide a simplified, yet up-to-date information regarding the different management options for those diabetic chronic kidney failure patients.
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Affiliation(s)
- Ahmed Aref
- Department of Nephrology, Sur Hospital, Sur 411, Oman
- Faculty of Health and Science, Institute of Learning and Teaching, University of Liverpool, Liverpool L69 3GB, United Kingdom
| | - Tariq Zayan
- Department of Nephrology, Sur Hospital, Sur 411, Oman
- Faculty of Health and Science, Institute of Learning and Teaching, University of Liverpool, Liverpool L69 3GB, United Kingdom
| | - Ravi Pararajasingam
- Faculty of Health and Science, Institute of Learning and Teaching, University of Liverpool, Liverpool L69 3GB, United Kingdom
- Department of Transplantation, Sheffield Teaching Hospitals, Sheffield S5 7AU, United Kingdom
| | - Ajay Sharma
- Faculty of Health and Science, Institute of Learning and Teaching, University of Liverpool, Liverpool L69 3GB, United Kingdom
- Renal Medicine, Royal Liverpool University Hospitals, Liverpool L7 8XP, United Kingdom
| | - Ahmed Halawa
- Faculty of Health and Science, Institute of Learning and Teaching, University of Liverpool, Liverpool L69 3GB, United Kingdom
- Department of Transplantation Surgery, Sheffield Teaching Hospitals, Sheffield S5 7AU, United Kingdom
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24
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Abstract
Pancreas transplantation is currently the most effective and curative treatment for complicated type 1 diabetes mellitus, providing durable and physiological insulin-independent euglycemia, preventing worsening or ameliorating of diabetic complications, and improving quality of life. Currently, more than 31 000 pancreas transplantation procedures have been performed, mainly in the United States. Pancreas transplantation is still an uncommon procedure in Asia, mainly performed in Korea, Taiwan, and Japan. The first pancreas (simultaneous pancreas and kidney transplantation) transplantation was successfully initiated at Taipei Veterans General Hospital on September 19, 2003, and we are the first team to be qualified to perform human pancreas procurement and transplantation by Taiwan Department of Health on August 31, 2007. The technique success rate in our pancreas transplantation is 97%, with 1-year pancreas graft survival rate of 95.8%, 5-year pancreas graft survival rate of 89.9%, and 10-year pancreas graft survival rate of 65.9%.
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25
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Anthony ML, Cravey KS, Atway SA. Development of Charcot Neuroarthropathy in Diabetic Patients who Received Kidney or Kidney-Pancreas Transplants. J Foot Ankle Surg 2019; 58:475-479. [PMID: 30765253 DOI: 10.1053/j.jfas.2018.09.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Indexed: 02/03/2023]
Abstract
Only a small percentage of the general diabetic population develops Charcot neuroarthropathy. Charcot arthropathy greatly increases the risk of foot complications. At our academic institution, there appeared to be an increased incidence of Charcot arthropathy in transplant patients. We hypothesized that Charcot neuroarthropathy incidence is higher in the diabetic patients who had received kidney or kidney-pancreas transplants. The charts of 1000 patients were reviewed from January 2000 to January 2011. Four hundred and eighty-seven patients were included in the study. Of these diabetic patients, 249 had received a kidney transplant and 238 a kidney-pancreas transplant. The data were analyzed for the incidence of Charcot in each group. Other risk factors and sequelae were also evaluated and analyzed. The incidence of Charcot development in the diabetic patients who had a kidney-pancreas transplant was 18.4%, 44 of 238 patients. This was significantly higher than the incidence in kidney transplant patients, which was 11.2%, 28 of 249 patients (p < .05). Peripheral arterial disease was a statistically significant independent risk factor for developing ulceration, osteomyelitis, and subsequent amputation. Type 1 diabetic patients developed Charcot at a higher rate that was also statistically significant compared with type 2 diabetic patients. In our study, diabetic patients who had undergone kidney-pancreas transplants were associated with higher risk for development of Charcot neuroarthropathy than kidney transplants alone. The incidence of Charcot development in both these transplant groups was also much higher than in the general diabetic population. This is of particular interest to clinicians and surgeons as both transplant groups were found to be high risk for subsequent foot ulceration, infection, and amputation.
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Affiliation(s)
- Michael L Anthony
- Assistant Professor, Podiatric Medicine and Surgery Residency Program, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Kimberly S Cravey
- Resident, Podiatric Medicine and Surgery Residency Program, The Ohio State University Wexner Medical Center, Columbus, OH.
| | - Said A Atway
- Assistant Professor, Podiatric Medicine and Surgery Residency Program, The Ohio State University Wexner Medical Center, Columbus, OH
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26
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Parajuli S, Alagusundaramoorthy S, Aziz F, Garg N, Redfield RR, Sollinger H, Kaufman D, Djamali A, Odorico J, Mandelbrot D. Outcomes of Pancreas Transplant Recipients With De Novo Donor-specific Antibodies. Transplantation 2019; 103:435-440. [PMID: 29994978 DOI: 10.1097/tp.0000000000002339] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Development of de novo donor-specific antibodies (dnDSA) has detrimental effects on graft survival in several types of solid organ transplants. However, limited information exists about the effect of dnDSA on pancreas transplant graft survival. METHODS We report our experience with pancreas recipients transplanted between January 01, 2005, and August 31, 2017. RESULTS We identified 541 pancreas transplant recipients, of which 121 developed dnDSA and 420 did not. Thirty-two percent developed dnDSA against HLA class I antigens, 56% developed against class II antigens, and 12% developed against both. Fifty-two percent of the patients in the dnDSA+ and 24% in the dnDSA- group underwent pancreas biopsy, mainly due to a rise in pancreatic enzymes. Rejection was found in 42% of the dnDSA+ group, and 20% of the dnDSA- group(P < 0.001). There were 36% uncensored graft failures in the dnDSA+ group and 17% uncensored failures in the dnDSA- group (P < 0.001). A similar trend was seen in death-censored graft failure between the groups. In univariate Cox regression analyses, male sex, older age, and recipients of simultaneous pancreas and kidney transplant were found to be protective for death-censored graft failure; multiple transplants, dnDSA, requirement for pancreas biopsy and presence of pancreas rejection were associated with increased risk of graft failure. In multivariate analysis, only older age and dnDSA were significantly associated with death-censored graft failure. CONCLUSIONS Our findings suggest that dnDSA in pancreas transplant recipients are associated with increased rates of rejection and graft failure. Timely detection of dnDSA through regular screening and early treatment of pancreas rejection may ultimately improve graft outcomes.
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Affiliation(s)
- Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Sayee Alagusundaramoorthy
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Fahad Aziz
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Neetika Garg
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Robert R Redfield
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Hans Sollinger
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Dixon Kaufman
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Arjang Djamali
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Jon Odorico
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Didier Mandelbrot
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
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27
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A steady decline in pancreas transplantation rates. Pancreatology 2019; 19:31-38. [PMID: 30448085 DOI: 10.1016/j.pan.2018.11.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 09/27/2018] [Accepted: 11/09/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES After years of growth in many pancreas transplant programs, UNOS has reported declining transplant numbers in the USA. This precipitating trend urges for an evaluation of the transplant numbers and scientific productivity in the Eurotransplant region and the UK. METHODS We performed a trend analysis of pancreas transplantation rates, between 1997 and 2016, adjusting for changes in population size, and an analysis of scientific publications in this field. We used information from the UNOS, Eurotransplant, and UK transplant registry and bibliometric information from the Web of Science database. RESULTS Between 2004 and 2016 there was an average annual decline in pancreas transplantation rates per million inhabitants of 3.3% in the USA and 2.5% in the Eurotransplant region. In the UK, transplant numbers showed an average annual decline of 1.0% from 2009 to 2016. Publications in Q1 journals showed an annual change of -2.1% and +20.1%, before 2004, and a change of -3.8% and -5.5%, between 2004 and 2016, for USA and Eurotransplant publications, respectively. CONCLUSIONS Adjusting pancreas transplantation rates for changes in population size showed a clear decline in transplant numbers in both the USA and Eurotransplant region, with first signs of decline in the UK. Following this trend, the number of scientific publications in this field have declined worldwide.
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28
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Samoylova ML, Borle D, Ravindra KV. Pancreas Transplantation: Indications, Techniques, and Outcomes. Surg Clin North Am 2018; 99:87-101. [PMID: 30471744 DOI: 10.1016/j.suc.2018.09.007] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Pancreas transplantation treats insulin-dependent diabetes with or without concurrent end-stage renal disease. Pancreas transplantation increases survival versus no transplant, increases survival when performed as simultaneous pancreas-kidney versus deceased-donor kidney alone, and improves quality of life. Careful donor and recipient selection are paramount to good outcomes. Several technical variations exist for implantation: portal versus systemic vascular drainage and jejunal versus duodenal versus bladder exocrine drainage. Complications are most frequently technical in the first year and immunologic thereafter. Graft rejection is challenging to diagnose and is treated selectively. Islet cell transplantation currently has inferior outcomes to whole-organ pancreas transplantation.
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Affiliation(s)
- Mariya L Samoylova
- Department of Surgery, Duke University School of Medicine, DUMC Box 3443, Room M114, Yellow Zone, Duke South, Durham, NC 27710, USA
| | - Deeplaxmi Borle
- Department of Surgery, Division of Abdominal Transplant Surgery, Duke University School of Medicine, DUMC Box 3443, Room M114, Yellow Zone, Duke South, Durham, NC 27710, USA
| | - Kadiyala V Ravindra
- Department of Surgery, Division of Abdominal Transplant Surgery, Duke University School of Medicine, 330 Trent Drive Room 217, DUMC Box 3512, Durham, NC 27710, USA.
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29
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Giorgakis E, Mathur AK, Chakkera HA, Reddy KS, Moss AA, Singer AL. Solid pancreas transplant: Pushing forward. World J Transplant 2018; 8:237-251. [PMID: 30596031 PMCID: PMC6304337 DOI: 10.5500/wjt.v8.i7.237] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Revised: 11/10/2018] [Accepted: 11/15/2018] [Indexed: 02/05/2023] Open
Abstract
Pancreas transplant has evolved significantly in recent years. It has now become a viable treatment option on type 1 diabetic patients with poorly controlled diabetes on conventional treatment, insulin intolerance, hypoglycaemia unawareness, brittle diabetes and/ or end-stage kidney disease. The purpose of this review is to provide an overview of pancreas transplant historical origins and current barriers to broader utilization of pancreata for transplant, with a focus on areas for future improvement to better pancreas transplant care. Donor pancreata remain underutilized; pancreatic allograft discard rates remain close to 30% in the United States. Donations after cardiac death (DCD) pancreata are seldom procured. Study groups from Europe and the United Kingdom showed that procurement professionalization and standardization of technique, as well as development of independent regional procurement teams might increase organ procurement efficiency, decrease discards and increase pancreatic allograft utilization. Pancreas transplant programs should consider exploring pancreas procurement opportunities on DCD and obese donors. Selected type 2 diabetics should be considered for pancreas transplant. Longer follow-up studies need to be performed in order to ascertain the long-term cardiovascular and quality of life benefits following pancreas transplant; the outcomes of which might eventually spearhead advocacy towards broader application of pancreas transplant among diabetics.
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Affiliation(s)
- Emmanouil Giorgakis
- Division of Transplant, Department of Surgery, Mayo Clinic, Phoenix, AZ 85054, United States
- Department of Transplant, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
| | - Amit K Mathur
- Division of Transplant, Department of Surgery, Mayo Clinic, Phoenix, AZ 85054, United States
| | - Harini A Chakkera
- Division of Nephrology, Department of Internal Medicine, Mayo Clinic, Phoenix, AZ 85054, United States
| | - Kunam S Reddy
- Division of Transplant, Department of Surgery, Mayo Clinic, Phoenix, AZ 85054, United States
| | - Adyr A Moss
- Division of Transplant, Department of Surgery, Mayo Clinic, Phoenix, AZ 85054, United States
| | - Andrew L Singer
- Division of Transplant, Department of Surgery, Mayo Clinic, Phoenix, AZ 85054, United States
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30
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Czerwińska M, Gniewkiewicz MS, Gozdowska J, Wyzgał J, Grochowiecki T, Nazarewski S, Kosieradzki M, Durlik M. Analysis of Hospitalizations in Simultaneous Pancreas-Kidney Transplant Recipients: A Single-center Experience in Poland. Transplant Proc 2018; 50:2132-2135. [PMID: 30177124 DOI: 10.1016/j.transproceed.2018.02.142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Accepted: 02/19/2018] [Indexed: 10/17/2022]
Abstract
BACKGROUND End-stage renal disease due to type 1 diabetes mellitus appears to be a regular indication for simultaneous pancreas and kidney transplantation (SPKT). Although transplantation improves a patient's health condition, it does not mean that all complications will be eliminated. METHODS We performed a retrospective analysis of 73 patients who underwent SPKT and follow-up between 1988 and 2015 at our institute. The number, duration, and reasons for hospitalization at 1, 5, 10, and 15 years after SPKT were analyzed. RESULTS The average number of hospitalizations at 1, 5, 10, 15 years after SPKT were 1.66, 0.39, 0.36, and 0.33, respectively. The main reason for hospitalization over the 15-year period was infections, at 32.4% (SD, 6.8%). Within the first year after SPKT, 6.8% of hospital admissions were caused by cytomegalovirus (CMV) infection. Over time, the percentage of hospitalizations for cardiovascular complications increased from 0.6% at 1 year to 29% at 12-15 years. Incidence of hospitalization due to cardiovascular complications correlated with a longer period of dialysis and a diagnosis of ischemic heart disease before transplant (r = 0.56, P = .004; r = 0.54, P < .0001, respectively). At 12-15 years after transplantation, 18.2% of hospitalizations were caused by secondary complications of diabetes. CONCLUSION The most common reason for hospitalization after SPKT is infectious complications. In the first year posttransplant, there is a high percentage of CMV infections. Hospitalization associated with cardiovascular complications was found to be most common in the latter follow-up period and showed a correlation with longer dialysis period.
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Affiliation(s)
- M Czerwińska
- Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - M S Gniewkiewicz
- Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - J Gozdowska
- Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
| | - J Wyzgał
- Department of Nephrology Nursing, Medical University of Warsaw, Warsaw, Poland
| | - T Grochowiecki
- Department of General, Vascular and Transplant Surgery, Medical University of Warsaw, Warsaw, Poland
| | - S Nazarewski
- Department of General, Vascular and Transplant Surgery, Medical University of Warsaw, Warsaw, Poland
| | - M Kosieradzki
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - M Durlik
- Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
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31
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Evaluation of a single-pass with biphasic intravenous contrast medium injection CT protocol for the assessment of complications post-simultaneous pancreas-kidney transplant. Clin Radiol 2018; 73:677.e7-677.e11. [PMID: 29625745 DOI: 10.1016/j.crad.2018.02.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 02/06/2018] [Indexed: 11/22/2022]
Abstract
AIM To evaluate the use of a single-pass with biphasic intravenous contrast medium injection computed tomography (CT) protocol to provide diagnostic quality CT studies for the assessment of complications post-simultaneous pancreas-kidney transplant (SPK). MATERIALS AND METHODS This was an audit of practice and the need for informed consent was waived. The protocol was used in consecutive patients undergoing CT to exclude intra-abdominal sepsis post-SPK between June and December 2015. Single CT acquisition of the abdomen and pelvis was initiated 70 seconds after the start of biphasic contrast medium injection (66 ml at 1.2 ml/s, followed by 34 ml at 2.4 ml/s, 370 mg iodine/ml). The named transplant pancreas vessels were identified and the attenuation values of the blood within were measured. Diagnostic quality was confirmed if values were >211 HU and >80 HU in the arteries and veins, respectively. RESULTS Thirteen CT studies were performed in 10 patients. CT studies were excluded due to complete pancreatic necrosis, and transplant superior mesenteric artery (SMA) thrombus with pancreatic head ischaemia causing effacement of the transplant superior mesenteric vein (SMV). Diagnostic quality of the analysed CT studies were confirmed with mean attenuation value of blood >211 HU in the transplant pancreatic arteries (SMA=259.0±51.4 HU, splenic artery=245.3±37.5 HU), and >80 HU in the pancreatic veins (SMV=195.4±36.2 HU, splenic vein=185.1±54.2 HU). CONCLUSION Diagnostic quality CT studies were obtained using the single-pass CT protocol. Radiation exposure to patients may be reduced with this protocol, while permitting simultaneous assessment of parenchymal and vascular complications post-SPK.
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Kostakis A, Theodoropoulou E. Diabetes Mellitus and Renal Transplantation: A Short Update. EXP CLIN TRANSPLANT 2018. [PMID: 29527981 DOI: 10.6002/ect.tond-tdtd2017.l25] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Affiliation(s)
- Alkiviadis Kostakis
- From the Department of Surgery and Transplantation, University of Athens, Athens, Greece
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33
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Pancreas Transplantation at a Single Latin-American Center; Overall Results with Type 1 and Type 2 Diabetes Mellitus. Transplant Proc 2018; 50:1475-1481. [PMID: 29880374 DOI: 10.1016/j.transproceed.2018.03.022] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 03/06/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Simultaneous pancreas-kidney transplantation (SPK) has become the treatment of choice for type 1 diabetes mellitus (T1DM) patients with chronic renal failure. Type 2 diabetes mellitus (T2DM), was once considered to be a contraindication for pancreas transplantation; however, it has been accepted as a new indication, under strict criteria. Although favorable results have increase the indication for T2DM in developed countries, there have been no reports of long-term results for this indication from Latin American centers. METHODS From April 2008 to March 2016, patients receiving SPK or pancreas transplant alone (PTA) for T2DM were included and compared with T1DM recipients. Variables were compared between groups with the use of χ2 and t tests; Kaplan-Meier with log rank was used for patient and graft survivals; P < .05 was considered to be significant. RESULTS A total of 45 SPK and 1 PTA were performed, 35 (76.1%) for T1DM and 11 (24.5%) for T2DM. Mean pre-transplantation C-peptide was significantly higher in the T2DM group (P = .01); HbA1c was higher in the T1DM group (P = .03). No differences were found in weight, body mass index, and pre-transplantation glycemia. Patient survivals for T1DM recipients were 88.2% and 84.8% at 1 and 5 years, respetively, versus 100% and 74.1% for T2DM recipients (P = .87). CONCLUSIONS Our initial prospective experience in a single Latin American center showed that medium- and long-term outcomes for T1DM and T2DM individuals receiving pancreas transplants are similar, under strict selection criteria.
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Techniques of pancreas graft salvage/indications for allograft pancreatectomy. Curr Opin Organ Transplant 2017; 21:405-11. [PMID: 27058314 DOI: 10.1097/mot.0000000000000318] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE OF REVIEW Despite improvements in pancreas allograft outcome, graft complications remain a significant cause of morbidity and mortality. This review analyses the issues involved in the management of conditions that may require graft pancreatectomy, including the indications and techniques for graft salvage. RECENT FINDINGS With early recognition of graft complications, liberal use of radiological interventions, improved infection control, access to critical care and innovative surgical techniques, graft salvage is now feasible in many circumstances where graft pancreatectomy would previously have been necessary. SUMMARY The outcome of pancreas transplantation continues to improve with advances in the management of graft-threatening complications.
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Abstract
BACKGROUND Successful pancreas transplantation requires surgical expertise and multidisciplinary medical management. The impact of transplant center volume on pancreas allograft survival remains unclear. METHODS We examined Organ Procurement and Transplantation Network data on 11 568 simultaneous pancreas-kidney (SPK) and 4308 solitary pancreas (pancreas transplant alone and pancreas after kidney) transplants between 2000 and 2013. RESULTS Average annual transplant center volume was categorized by tertiles into low, medium, and high volume, respectively, as follows: 1 to 6 (n = 3861), 7 to 13 (n = 3891), and 14 to 34 (n = 3888) for SPK, and 1 to 3 (n = 1417), 4 to 10 (n = 1518), and 11 to 33 (n = 1377) for solitary pancreas transplants. Favorable donor characteristics were seen in low-volume centers. For SPK transplantation, low (adjusted hazard ration [aHR], 1.55, 95% confidence interval [CI], 1.34-1.8) and medium (aHR, 1.24; 95% CI, 1.07-1.44) center volumes were associated with a higher risk of early pancreas graft failure at 3 months. The increased risk associated with low center volume extended to 1, 5, and 10 years. For solitary pancreas transplants, low, but not medium, center volume was associated with a higher risk of early pancreas graft failure at 3 months (aHR, 1.56; 95% CI, 1.232-1.976), and this risk persisted over 10 years. Patients transplanted at high-volume centers had better pancreas survival rates across all categories of the Pancreas Donor Risk Index. CONCLUSION On average, low center volume were associated with higher risk for pancreas failure. Future studies should seek to identify care processes that support optimal outcomes after pancreas transplantation irrespective of center volume.
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Al-Adra D, McGilvray I, Goldaracena N, Spetzler V, Laurence J, Norgate A, Marquez M, Greig P, Sapisochin G, Schiff J, Singh S, Selzner M, Cattral M. Preserving the Pancreas Graft: Outcomes of Surgical Repair of Duodenal Leaks in Enterically Drained Pancreas Allografts. Transplant Direct 2017; 3:e179. [PMID: 28706982 PMCID: PMC5498020 DOI: 10.1097/txd.0000000000000698] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Accepted: 04/16/2017] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Duodenal leak remains a major cause of morbidity and graft loss in pancreas transplant recipients. The role and efficacy of surgical and image-guided interventions to salvage enterically drained grafts with a duodenal leak has yet to be defined. METHODS We investigated the incidence, treatment, and outcome of duodenal leak in 426 pancreas transplantation recipients from 2000 to 2015. RESULTS Duodenal leak developed in 33 (7.8%) recipients after a median follow-up of 5.3 (range, 0.5-15.2) years. Most leaks occurred during the first year (n = 22; 67%), and most were located near the proximal and distal duodenal staple line. Graft pancreatectomy was performed in 8 patients as primary therapy because of unfavorable local and/or systemic conditions. Salvage was attempted in 25 patients using percutaneous drainage (n = 4), surgical drainage (n = 4), or surgical repair (n = 17). Percutaneous or surgical drainage failed to control the leak in 7 of these 8 patients, and all 7 ultimately required graft pancreatectomy for persistent leak and sepsis. Surgical repair salvaged 14 grafts, and 13 grafts continue to function after a median follow-up of 2.9 (range, 1.1-6.3) years after repair. CONCLUSIONS Our study shows that in selected patients a duodenal leak can be repaired successfully and safely in enterically drained grafts.
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Affiliation(s)
- David Al-Adra
- Department of Surgery, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Ian McGilvray
- Department of Surgery, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Nicolas Goldaracena
- Department of Surgery, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Vinzent Spetzler
- Department of Surgery, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Jerome Laurence
- Royal Prince Alfred Institute of Academic Surgery, University of Sydney, Sydney, Australia
| | - Andrea Norgate
- Department of Surgery, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Max Marquez
- Department of Surgery, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Paul Greig
- Department of Surgery, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- Department of Surgery, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Jeffrey Schiff
- Department of Medicine, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Sunita Singh
- Department of Medicine, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Markus Selzner
- Department of Surgery, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Mark Cattral
- Department of Surgery, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
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Survival Advantage of Kidney-Pancreas vs. Kidney Alone Transplant in the Modern Era. CURRENT TRANSPLANTATION REPORTS 2017. [DOI: 10.1007/s40472-017-0151-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Abstract
PURPOSE OF REVIEW Patients with type 1 diabetes and end stage renal disease face a complex choice when considering the relative risks and benefits of kidney transplant alone with or without subsequent pancreas after kidney transplant (PAK) or simultaneous kidney pancreas transplant (SPK). RECENT FINDINGS SPK is considered the optimal treatment regarding long-term patient survival, but when also faced with the option of living donor kidney transplant with the potential for PAK later, the ideal option is less clear. SUMMARY This review summarizes the current literature regarding SPK, living donor kidney transplant alone, and PAK transplant outcomes and examines the relative risks of pre- and posttransplant variables that impact patient and graft survival to help inform this complex treatment decision.
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Barlow AD, Saeb-Parsy K, Watson CJE. An analysis of the survival outcomes of simultaneous pancreas and kidney transplantation compared to live donor kidney transplantation in patients with type 1 diabetes: a UK Transplant Registry study. Transpl Int 2017; 30:884-892. [PMID: 28319322 DOI: 10.1111/tri.12957] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Revised: 11/18/2016] [Accepted: 03/15/2017] [Indexed: 11/30/2022]
Abstract
Transplant options for patients with type 1 diabetes and end-stage renal disease (ESRD) include deceased donor kidney, live donor kidney (LDK) and simultaneous pancreas-kidney (SPK) transplantation. The aim of this study was to compare outcomes between LDK and SPK for patients with type 1 diabetes and ESRD in the UK. Data on all SPK (n = 1739) and LDK (n = 385) transplants performed between January 2001 and December 2014 were obtained from the UK Transplant Registry. Unadjusted patient and kidney graft survival were calculated using the Kaplan-Meier method. Multivariate analysis of kidney graft and patient survival was performed using Cox proportional hazards regression. There was no significant difference in patient (P = 0.435) or kidney graft survival (P = 0.204) on univariate analysis. On multivariate analysis there was no association between LDK/SPK and patient survival [HR 0.71 (0.47-1.06), P = 0.095]. However, LDK was associated with an overall lower risk for kidney graft failure [HR 0.60 (0.38-0.94), P = 0.025]. SPK recipients with a functioning pancreas graft had significantly better kidney graft and patient survival than LDK recipients or those with a failed pancreas graft. SPK transplantation does not confer an overall survival advantage compared to LDK. However, those SPK recipients with a functioning pancreas have significantly better outcomes.
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Affiliation(s)
- Adam D Barlow
- Leeds Transplant Centre, St. James's University Hospital, Leeds, UK
| | - Kourosh Saeb-Parsy
- Department of Surgery and NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.,NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Cambridge, UK
| | - Christopher J E Watson
- Department of Surgery and NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.,NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Cambridge, UK
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Lindahl JP, Hartmann A, Aakhus S, Endresen K, Midtvedt K, Holdaas H, Leivestad T, Horneland R, Øyen O, Jenssen T. Long-term cardiovascular outcomes in type 1 diabetic patients after simultaneous pancreas and kidney transplantation compared with living donor kidney transplantation. Diabetologia 2016; 59:844-52. [PMID: 26713324 DOI: 10.1007/s00125-015-3853-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Accepted: 12/14/2015] [Indexed: 01/30/2023]
Abstract
AIMS/HYPOTHESIS Mortality due to cardiovascular disease (CVD), particularly coronary artery disease (CAD), is high in type 1 diabetic patients with end-stage renal disease (ESRD). We aimed to determine whether normoglycaemia, as achieved by successful simultaneous pancreas and kidney (SPK) transplantation, could improve long-term outcomes compared with living donor kidney-alone (LDK) transplantation. METHODS We studied 486 type 1 diabetic patients with ESRD who underwent a first SPK (n = 256) or LDK (n = 230) transplant between 1983 and 2012 and were followed to the end of 2014. Data were retrieved from the Norwegian Renal Registry and hospital records. Kaplan-Meier plots and multivariate Cox regression, with correction for recipient, donor and transplant factors, were used to examine potential associations between transplant type and all-cause and CVD- and CAD-related mortality. RESULTS Median follow-up time was 7.9 years (interquartile range 4.3, 12.9). The adjusted HR for CVD-related deaths in SPK recipients compared with LDK recipients was 0.63 (95% CI 0.40, 0.99; p = 0.047), while the HRs for all-cause and CAD-related mortality were 0.81 (95% CI 0.57, 1.16; p = 0.25) and 0.63 (95% CI 0.36, 1.12; p = 0.12), respectively. Compared with the LDK group, SPK recipients were younger and received grafts from younger donors. Cardiovascular mortality was higher in patients transplanted between 1983 and 1999 compared with those who received their grafts in subsequent years. CONCLUSIONS/INTERPRETATION In patients with type 1 diabetes and ESRD, SPK transplantation was associated with reduced long-term cardiovascular mortality compared with LDK transplantation.
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Affiliation(s)
- Jørn P Lindahl
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
- Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372, Oslo, Norway.
| | - Anders Hartmann
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372, Oslo, Norway
| | - Svend Aakhus
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Knut Endresen
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Karsten Midtvedt
- Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372, Oslo, Norway
| | - Hallvard Holdaas
- Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372, Oslo, Norway
| | - Torbjørn Leivestad
- Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372, Oslo, Norway
| | - Rune Horneland
- Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372, Oslo, Norway
| | - Ole Øyen
- Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372, Oslo, Norway
| | - Trond Jenssen
- Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372, Oslo, Norway
- Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway
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Jeon HJ, Koo TY, Han M, Kim HJ, Jeong JC, Park H, Ha J, Kim SJ, Ahn C, Park JB, Yang J. Outcomes of dialysis and the transplantation options for patients with diabetic end-stage renal disease in Korea. Clin Transplant 2016; 30:534-44. [PMID: 26914661 DOI: 10.1111/ctr.12719] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/17/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND The best therapeutic option for diabetic end-stage renal disease (DMESRD) has not been established among living donor kidney transplantation (LDKT), deceased donor kidney transplantation (DDKT), simultaneous pancreas and kidney transplantation (SPK), and dialysis. METHODS We retrospectively analyzed the outcomes of DMESRD patients at two Korean centers from February 2000 to December 2011. RESULTS Among 674 patients, 295 underwent kidney transplantation (LDKT, 175; DDKT, 72; and SPK, 48), while 379 were still on dialysis. The dialysis group had a higher mortality rate than the transplantation group. From the time after dialysis initiation, LDKT group had a better patient survival rate than DDKT registration group and SPK registration group. From the time after transplantation, LDKT had a better patient survival rate than DDKT; however, there was no significant difference between LDKT and SPK. In SPK, patient survival and kidney or pancreas graft survival rates were not different between types 1 and 2 DMESRD. CONCLUSION LDKT is better than waiting for SPK/DDKT in DMESRD patients, if a living donor is available, and this conclusion may be unique to Korea where waiting time for SPK is long. SPK can be used in non-obese Asians with type 2 as well as type 1 DMESRD.
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Affiliation(s)
- Hee Jung Jeon
- Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Tai Yeon Koo
- Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Miyeun Han
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ha Jin Kim
- Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jong Cheol Jeong
- Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyojun Park
- Department of Surgery, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jongwon Ha
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sung Joo Kim
- Department of Surgery, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Curie Ahn
- Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jae Berm Park
- Department of Surgery, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jaeseok Yang
- Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea
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Chan GC, Tang SC. Diabetic nephropathy: landmark clinical trials and tribulations. Nephrol Dial Transplant 2016; 31:359-368. [DOI: 10.1093/ndt/gfu411] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
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King EA, Kucirka LM, McAdams-DeMarco MA, Massie AB, Al Ammary F, Ahmed R, Grams ME, Segev DL. Early Hospital Readmission After Simultaneous Pancreas-Kidney Transplantation: Patient and Center-Level Factors. Am J Transplant 2016; 16:541-9. [PMID: 26474070 PMCID: PMC6116541 DOI: 10.1111/ajt.13485] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Revised: 07/20/2015] [Accepted: 08/09/2015] [Indexed: 01/25/2023]
Abstract
Early hospital readmission is associated with increased morbidity, mortality, and cost. Following simultaneous pancreas-kidney transplantation, rates of readmission and risk factors for readmission are unknown. We used United States Renal Data System data to study 3643 adult primary first-time simultaneous pancreas-kidney recipients from December 1, 1999 to October 31, 2011. Early hospital readmission was any hospitalization within 30 days of discharge. Modified Poisson regression was used to determine the association between readmission and patient-level factors. Empirical Bayes statistics were used to determine the variation attributable to center-level factors. The incidence of readmission was 55.5%. Each decade increase in age was associated with an 11% lower risk of readmission to age 40, beyond which there was no association. Donor African-American race was associated with a 13% higher risk of readmission. Each day increase in length of stay was associated with a 2% higher risk of readmission until 14 days, beyond which each day increase was associated with a 1% reduction in the risk of readmission. Center-level factors were not associated with readmission. The high incidence of early hospital readmission following simultaneous pancreas-kidney transplant may reflect clinical complexity rather than poor quality of care.
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Affiliation(s)
- Elizabeth A. King
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Lauren M. Kucirka
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD,Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
| | - Mara A. McAdams-DeMarco
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD,Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
| | - Allan B. Massie
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD,Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
| | - Fawaz Al Ammary
- Department of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Rizwan Ahmed
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Morgan E. Grams
- Department of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Dorry L. Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD,Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
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Laurence JM, Barbas AS, Sapisochin G, Marquez MA, Bazerbachi F, Selzner M, Norgate A, McGilvray ID, Schiff J, Ross H, Cattral MS. The significance of pre-operative coronary interventions on outcome after pancreas transplantation. Clin Transplant 2015; 30:233-40. [PMID: 26700761 DOI: 10.1111/ctr.12681] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/15/2015] [Indexed: 11/28/2022]
Abstract
Pancreas transplant candidates are at very high risk of coronary vascular disease. We hypothesized that the requirement for pre-operative coronary intervention (PCI) may be associated with an adverse impact on short- and long-term outcomes. Retrospective analysis of 366 consecutive primary pancreas transplants was undertaken. Outcomes were compared between recipients who had undergone PCI (n = 48) and those who had not (n = 318). In 48% (23/48) of instances, the PCI was initiated by the transplant cardiology evaluation. The recipients undergoing PCI were older than those not undergoing PCI (47.6 yr vs. 41.9 yr, respectively, p < 0.0001). Although not statistically significant, there was a higher rate of post-operative major cardiovascular events (MCVE) in the PCI group (10.4%) compared with those not undergoing PCI (4.7%) (RR [95% CI]: 2.0 [0.90-4.5]; p = 0.17). In the long term, there were no differences in the rate of death with graft function (p = 0.77) or rejection (p = 0.17). There were no statistically significant differences between the groups with respect to patient (p = 0.54), kidney (p = 0.76), or pancreas (p = 0.63) graft survival. PCI is not a risk factor for short-term perioperative events, and long-term transplant outcomes are equivalent to patients not requiring PCI. PCI, by itself, should not be considered a contraindication for pancreas transplantation, but should raise awareness of perioperative risk.
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Affiliation(s)
- Jerome M Laurence
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.,RPA Institute of Academic Surgery, Royal Prince Alfred Hospital, University of Sydney, NSW, Australia
| | - Andrew S Barbas
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Gonzalo Sapisochin
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Max A Marquez
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Fateh Bazerbachi
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Markus Selzner
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Andrea Norgate
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Ian D McGilvray
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Jeffrey Schiff
- Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Heather Ross
- RPA Institute of Academic Surgery, Royal Prince Alfred Hospital, University of Sydney, NSW, Australia
| | - Mark S Cattral
- Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
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Chakkera HA, Kudva YC, Chang YHH, Heilman RL, Singer AL, Mathur AK, Hewitt WR, Khamash HA, Huskey JL, Katariya NN, Moss AA, Behmen S, Reddy KS. Glucose homeostasis after simultaneous pancreas and kidney transplantation: a comparison of subjects with C-peptide-positive non-type 1 diabetes mellitus and type 1 diabetes mellitus. Clin Transplant 2015; 30:52-9. [DOI: 10.1111/ctr.12658] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/13/2015] [Indexed: 11/30/2022]
Affiliation(s)
| | - Yogish C. Kudva
- Division of Endocrinology and Metabolic Diseases; Mayo Clinic; Rochester MN USA
| | - Yu-Hui H. Chang
- Department of Research Biostatistics; Mayo Clinic; Phoenix AZ USA
| | | | | | - Amit K. Mathur
- Division of Transplant Surgery; Mayo Clinic; Phoenix AZ USA
| | | | | | | | | | - Adyr A. Moss
- Division of Transplant Surgery; Mayo Clinic; Phoenix AZ USA
| | | | - Kunam S. Reddy
- Division of Transplant Surgery; Mayo Clinic; Phoenix AZ USA
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Rodríguez-Villar C, Conget I, Ferrer-Fàbrega J, Paredes D, Ruíz A, Roque R, Rull R, López-Boado M, Ricart MJ, Garcia R, Adalia R. Successful Pancreas Transplantation From a Deceased Donor Intoxicated With Oral Antidiabetic Agent: A Case Report. Transplant Proc 2015; 47:2404-6. [PMID: 26518941 DOI: 10.1016/j.transproceed.2015.08.028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Simultaneous kidney pancreas transplantation (SKP) is a common procedure for the patient with long-term type 1 diabetes mellitus (DM) with terminal renal failure. It is unusual to consider the pancreas from a deceased donor who died after an acute intoxication with oral antidiabetic agent (OAA), which would suggest an abnormal functionality of the organ and preclude the potential use of the graft. We present a case of a successful pancreatic transplantation from a donor who died of acute cerebral edema secondary to severe hypoglycemia induced by OAA acute intoxication.
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Affiliation(s)
| | - I Conget
- Unidad de Diabetes, Servicio de Endocrinología y Nutición, Barcelona, Spain
| | - J Ferrer-Fàbrega
- Cirugía Hepato-Bilio-Pancreática y Trasplante de Hígado y Páncreas, Barcelona, Spain
| | - D Paredes
- Sección de Donación y Coordinación de Trasplantes, Barcelona, Spain
| | - A Ruíz
- Sección de Donación y Coordinación de Trasplantes, Barcelona, Spain
| | - R Roque
- Sección de Donación y Coordinación de Trasplantes, Barcelona, Spain
| | - R Rull
- Cirugía Hepato-Bilio-Pancreática y Trasplante de Hígado y Páncreas, Barcelona, Spain
| | - M López-Boado
- Cirugía Hepato-Bilio-Pancreática y Trasplante de Hígado y Páncreas, Barcelona, Spain
| | - M J Ricart
- Unidad de Trasplante Renal, Barcelona, Spain
| | - R Garcia
- Cirugía Hepato-Bilio-Pancreática y Trasplante de Hígado y Páncreas, Barcelona, Spain
| | - R Adalia
- Sección de Donación y Coordinación de Trasplantes, Barcelona, Spain
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Clinical Practice Guideline on management of patients with diabetes and chronic kidney disease stage 3b or higher (eGFR <45 mL/min). Nephrol Dial Transplant 2015; 30 Suppl 2:ii1-142. [PMID: 25940656 DOI: 10.1093/ndt/gfv100] [Citation(s) in RCA: 96] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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50
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Hudson A, Bradbury L, Johnson R, Fuggle SV, Shaw JAM, Casey JJ, Friend PJ, Watson CJE. The UK Pancreas Allocation Scheme for Whole Organ and Islet Transplantation. Am J Transplant 2015; 15:2443-55. [PMID: 25943412 DOI: 10.1111/ajt.13284] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2014] [Revised: 02/01/2015] [Accepted: 02/23/2015] [Indexed: 01/25/2023]
Abstract
In order to develop a national allocation scheme for donor pancreases, factors affecting waiting time and transplant outcomes in the United States (US) and United Kingdom (UK) were analyzed and compared. Blood group, sensitization, dialysis requirement, and whether the patient was waiting for a kidney and pancreas or pancreas alone affected waiting time in both countries; ethnicity and body mass index (BMI) also affected waiting time in the US. Ninety-day pancreas survival was similar in the UK and US, and was poorer for patients receiving a pancreas alone, with older donors, higher BMI and longer duration of ischemia in both countries. Factors affecting outcome, together with published data on factors affecting islet transplantation, informed the development of a points based allocation scheme for deceased donor pancreases in the UK providing equitable access for both whole organ and islet recipients through a single waiting list. Analysis of the allocation scheme 3 years after its introduction in December 2010 showed that the results were broadly as simulated, with a significant reduction in the number of long waiting patients and an increase in the number of islet transplants. There remains a surplus of highly sensitized patients in the waiting list, which the scheme should address in time.
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Affiliation(s)
- A Hudson
- Organ Donation and Transplantation Directorate, NHS Blood and Transplant, Bristol, England
| | - L Bradbury
- Organ Donation and Transplantation Directorate, NHS Blood and Transplant, Bristol, England
| | - R Johnson
- Organ Donation and Transplantation Directorate, NHS Blood and Transplant, Bristol, England
| | - S V Fuggle
- Organ Donation and Transplantation Directorate, NHS Blood and Transplant, Bristol, England.,The Oxford Transplant Center, Churchill Hospital, Headington, Oxford, England
| | - J A M Shaw
- Institute of Cellular Medicine (Diabetes), The Medical School, Newcastle-upon-Tyne, England
| | - J J Casey
- Scottish Islet Transplant Unit, The Royal Infirmary, Edinburgh, Scotland
| | - P J Friend
- The Oxford Transplant Center, Churchill Hospital, Headington, Oxford, England
| | - C J E Watson
- University Department of Surgery, Addenbrooke's Hospital, Cambridge and the NIHR Cambridge Biomedical Research Center, England
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