RESUMO
The overall number of pancreas transplants decreased slightly, from 1027 in 2018 to 1015, in 2019, up from a nadir of 947 in 2015. However, the number of simultaneous pancreas-kidney transplants (SPKs) increased in 2019, with a corresponding drop in pancreas-after-kidney transplants (PAKs) and pancreas transplants alone (PTAs). New waitlist registrations increased to 1772 in 2019, from 1606 in 2018. This was predominately driven by SPK listings, and those with type 2 diabetes. Waiting time for SPK decreased by 2 months, to a median of 12 months in 2019, but PTA recipient mean waiting time remained substantially higher, at 24 months, in 2018. Both short- and long-term outcomes, including patient survival, kidney graft survival, and acute rejection-free graft survival, have shown consistent improvement over the last decade. Pancreas graft survival data with the uniform definition of allograft failure is being collected by the Organ Procurement and Transplant Network (OPTN) and will be included in a future report.
Assuntos
Diabetes Mellitus Tipo 2 , Transplante de Pâncreas , Obtenção de Tecidos e Órgãos , Sobrevivência de Enxerto , Humanos , PâncreasRESUMO
The overall number of pancreas transplants continued to increase to 1027 in 2018, after a nadir of 947 in 2015. New additions to waiting list remained stable, with 1485 candidates added in 2018. Proportions of patients with type II diabetes waiting for transplant (14.6%) and undergoing transplant (14.8%) have steadily increased since 2016. Waiting times for simultaneous pancreas/kidney transplant have decreased; median months to transplant was 13.5 for simultaneous pancreas/kidney transplant and 19.7 for pancreas transplant alone in 2018. Outcomes, including patient and kidney survival, as well as rejection rates, have improved consistently over the past several years. Pancreas graft survival data are being collected by the Organ Procurement and Transplantation Network and will be included in a future report once there are sufficient cohorts for analysis.
Assuntos
Transplante de Pâncreas/estatística & dados numéricos , Doadores de Tecidos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/métodos , Listas de Espera , Sobrevivência de Enxerto , Humanos , Estados UnidosRESUMO
In 2017, 1492 patients were added to the pancreas transplant waiting list, 964 listed as active, a slight increase from 2016. This is significant because for the first time in the past decade, the steady downward trend in additions to the waiting list has been reversed. Proportions of pancreas donors with cerebrovascular accident as cause of death decreased, with a concomitant increase in proportions with anoxia and head trauma. This is partly a result of the national opioid crisis, and it reflects increasing use of younger donors for pancreas transplant. The 2017 outcome report remains compromised by previous variation in reporting graft failure. Although the OPTN Pancreas Transplantation Committee has approved more precise definitions of pancreas graft failure, implementation of these definitions took place recently, and the data are not reflected in this report.
Assuntos
Sobrevivência de Enxerto , Transplante de Pâncreas/métodos , Sistema de Registros/estatística & dados numéricos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Relatórios Anuais como Assunto , Humanos , Estados Unidos , Listas de EsperaRESUMO
The number of pancreas transplants performed in the United States increased by 7.0% in 2016 over the previous year, the first such increase in more than a decade, largely attributable to an increase in simultaneous kidney pancreas transplants. Transplant rates increased in 2016, and mortality on the waiting list decreased. The declining enthusiasm for pancreas after kidney (PAK) transplants persisted. The uniform definition of graft failure was approved by the OPTN Board of Directors in 2015 and will be implemented in early 2018. Meanwhile, SRTR continues to refrain from reporting pancreas graft failure data. The OPTN/UNOS Pancreas Transplantation Committee is seeking to broaden allocation of pancreata across compatible ABO blood types in a proposal out for public comment July 31 to October 2, 2017. A new initiative to provide guidance on the benefits of PAK transplants is also out for public comment.
Assuntos
Relatórios Anuais como Assunto , Sobrevivência de Enxerto , Transplante de Pâncreas , Obtenção de Tecidos e Órgãos , Listas de Espera , Humanos , Sistema de Registros , Doadores de Tecidos , Estados UnidosRESUMO
The intent of this National Institutes of Health-sponsored study was to compare a belatacept-based immunosuppressive regimen with a maintenance regimen of tacrolimus and mycophenolate. Nineteen primary, Epstein-Barr virus-immune renal transplant recipients with a negative cross-match were randomized to one of three groups. All patient groups received perioperative steroids and maintenance mycophenolate mofetil. Patients in groups 1 and 2 were induced with alemtuzumab and maintained on tacrolimus or belatacept, respectively. Patients in group 3 were induced with basiliximab, received 3 mo of tacrolimus, and maintained on belatacept. There was one death with a functioning allograft due to endocarditis (group 1). There were three graft losses due to vascular thrombosis (all group 2) and one graft loss due to glomerular disease (group 1). Biopsy-proven acute cellular rejection was more frequent in the belatacept-treated groups, with 10 treated episodes in seven participants compared with one episode in group 1; however, estimated GFR was similar between groups at week 52. There were no episodes of posttransplant lymphoproliferative disorder or opportunistic infections in any group. Protocol enrollment was halted prematurely because of a high rate of serious adverse events. Such negative outcomes pose challenges to clinical investigators, who ultimately must weigh the risks and benefits in randomized trials.
Assuntos
Abatacepte/uso terapêutico , Corticosteroides/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim , Adolescente , Adulto , Idoso , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Islet transplantation offers a minimally invasive approach for ß cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet reinfusions from distinct donors, increasing the risk of allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the United States; however, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear. We describe a case series of seven patients undergoing solid organ pancreas transplant following islet graft failure with long-term follow-up of pancreatic graft survival and renal function. Despite highly variable panel reactive antibody levels prior to pancreas transplant (mean 27 ± 35%), all seven patients achieved stable and durable insulin independence with a mean follow-up of 6.7 years. Mean hemoglobin A1c values improved significantly from postislet, prepancreas levels (mean 8.1 ± 1.5%) to postpancreas levels (mean 5.3 ± 0.1%; p = 0.0022). Three patients experienced acute rejection episodes that were successfully managed with thymoglobulin and methylprednisolone, and none of these preuremic type 1 diabetic recipients developed stage 4 or 5 chronic kidney disease postoperatively. These results support pancreas-after-islet transplantation with aggressive immunosuppression and protocol biopsies as a viable strategy to restore insulin independence after islet graft failure.
Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Rejeição de Enxerto/prevenção & controle , Transplante das Ilhotas Pancreáticas , Transplante de Pâncreas , Adulto , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Adulto JovemRESUMO
The number of pancreas transplants performed in the United States stabilized over the last 3 years after nearly a decade of steady decline. Numbers of new additions to the list also stabilized during the same period. Notably, the persistent decline in pancreas after kidney transplants also seems to have abated, at least for now. The first full year of data after implementation of the new pancreas allocation system revealed no change in the distribution of organs between simultaneous pancreas-kidney (SPK) transplant and pancreas transplant alone. The percentage of kidneys used in SPK transplants was also unchanged. While a uniform definition of pancreas graft failure was approved in June 2015, it is awaiting implementation. Meanwhile, SRTR will refrain from publishing pancreas graft failure data in the program-specific reports. Therefore, it is difficult to track trends in outcomes after pancreas transplant over the past 2 years. New initiatives by the OPTN/UNOS Pancreas Transplantation Committee include facilitated pancreas allocation and broadened allocation of pancreata across compatible ABO blood types to increase organ utilization.
Assuntos
Relatórios Anuais como Assunto , Sobrevivência de Enxerto , Transplante de Pâncreas , Alocação de Recursos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Humanos , Imunossupressores , Resultado do Tratamento , Estados Unidos , Listas de EsperaRESUMO
Few current studies compare the outcomes of islet transplantation alone (ITA) and pancreas transplantation alone (PTA) for type 1 diabetes (T1D). We examined these two beta cell replacement therapies in nonuremic patients with T1D with respect to safety, graft function and cost. Sequential patients received PTA (n = 15) or ITA (n = 10) at our institution. Assessments of graft function included duration of insulin independence; glycemic control, as measured by hemoglobin A1c; and elimination of severe hypoglycemia. Cost analysis included all normalized costs associated with transplantation and inpatient management. ITA patients received one (n = 6) or two (n = 4) islet transplants. Mean duration of insulin independence in this group was 35 mo; 90% were independent at 1 year, and 70% were independent at 3 years. Mean duration of insulin independence in PTA was 55 mo; 93% were insulin independent at 1 year, and 64% were independent at 3 years. Glycemic control was comparable in all patients with functioning grafts, as were overall costs ($138 872 for ITA, $134 748 for PTA). We conclude that with advances in islet isolation and posttransplant management, ITA can produce outcomes similar to PTA and represents a clinically viable option to achieve long-term insulin independence in selected patients with T1D.
Assuntos
Análise Custo-Benefício , Diabetes Mellitus Tipo 1/terapia , Transplante das Ilhotas Pancreáticas/economia , Tempo de Internação/estatística & dados numéricos , Transplante de Pâncreas/economia , Adulto , Diabetes Mellitus Tipo 1/economia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , SegurançaRESUMO
Kidney transplantation is the optimal treatment for children with end-stage renal disease. For children with undocumented immigration status, access to kidney transplantation is limited, and data on transplant outcomes in this population are scarce. The goal of the present retrospective single-center study was to compare outcomes after kidney transplantation in undocumented children with those of US citizen children. Undocumented residency status was identified in 48 (17%) of 289 children who received a kidney transplant between 1998 and 2010. In undocumented recipients, graft survival at 1 and 5 years posttransplantation was similar, and mean estimated glomerular filtration rate at 1 year was higher than that in recipients who were citizens. The risk of allograft failure was lower in undocumented recipients relative to that in citizens at 5 years posttransplantation, after adjustment for patient age, donor age, donor type, and HLA mismatch (p < 0.04). In contrast, nearly one in five undocumented recipients who reached 21 years of age lost their graft, primarily because they were unable to pay for immunosuppressive medications once their state-funded insurance had ended. These findings support the ongoing need for immigration policies for the undocumented that facilitate access to work-permits and employment-related insurance for this disadvantaged group.
Assuntos
Emigração e Imigração/estatística & dados numéricos , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Falência Renal Crônica/cirurgia , Transplante de Rim , Obtenção de Tecidos e Órgãos/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Emigração e Imigração/legislação & jurisprudência , Feminino , Taxa de Filtração Glomerular , Política de Saúde , Humanos , Incidência , Lactente , Masculino , Estudos Retrospectivos , Medição de Risco , Fatores Socioeconômicos , Doadores de Tecidos , Transplantados , Transplante Homólogo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The shipment of human islets (IE) from processing centers to distant laboratories is beneficial for both research and clinical applications. The maintenance of islet viability and function in transit is critically important. Gas-permeable silicone rubber membrane (SRM) vessels reduce the risk of hypoxia-induced death or dysfunction during high-density islet culture or shipment. SRM vessels may offer additional advantages: they are cost-effective (fewer flasks, less labor needed), safer (lower contamination risk), and simpler (culture vessel can also be used for shipment). METHOD: IE were isolated from two manufacturing centers and shipped in 10-cm(2) surface area SRM vessels in temperature- and pressure-controlled containers to a distant center after at least 2 days of culture (n = 6). Three conditions were examined: low density (LD), high density (HD), and a microcentrifuge tube negative control (NC). LD was designed to mimic the standard culture density for IE preparations (200 IE/cm(2)), while HD was designed to have a 20-fold higher tissue density, which would enable the culture of an entire human isolation in 1-3 vessels. Upon receipt, islets were assessed for viability (measured by oxygen consumption rate normalized to DNA content [OCR/DNA)]), quantity (measured by DNA), and, when possible, potency and function (measured by dynamic glucose-stimulated insulin secretion measurements and transplants in immunodeficient B6 Rag(+/-) mice). Postshipment OCR/DNA was not reduced in HD vs LD and was substantially reduced in the NC condition. HD islets exhibited normal function postshipment. Based on the data, we conclude that entire islet isolations (up to 400,000 IE) may be shipped using a single, larger SRM vessel with no negative effect on viability and ex vivo and in vivo function.
Assuntos
Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas/fisiologia , Embalagem de Produtos/instrumentação , Elastômeros de Silicone , Manejo de Espécimes/instrumentação , Animais , Contagem de Células , Técnicas de Cultura de Células , Hipóxia Celular/fisiologia , Sobrevivência Celular , Humanos , Insulina/metabolismo , Secreção de Insulina , Camundongos , Consumo de Oxigênio/fisiologiaRESUMO
BACKGROUND: A recent study by Chen et al described a therapy for diabetes that involved electroporation of primary hepatocytes with human proinsulin cDNA, p3MTChins. Intrahepatic transplantation of treated hepatocytes into streptozotocin (STZ) murine and porcine models led to euglycemia, weight maintenance, and normal insulin production. We tested the repeatability of their basic experiments and transplantation technique and expanded the study to include an autoimmune model. METHODS: Hepatocytes were isolated from B6 mice, electroporated with p3MTChins, and glucose-challenged or were injected into hepatic or spleen parenchyma of STZ-diabetic B6 and non-obese diabetic mice. Outcomes included survival, serum glucose levels, insulin, and c-peptide release. Untransfected primary hepatocytes and mice transplanted with these cells served as controls. RESULTS: p3MTChins-hepatocytes secreted insulin during glucose challenge, but glucose levels did not change with increasing glucose concentrations. Direct hepatic injection led to high mortality rates. Mice that underwent intrasplenic injection survived for >50 days (control = 4 days) and had a mild but stable improvement in hyperglycemia. C-peptide in both mouse models was detectable but eventually declined to baseline in the non-obese diabetic mice. CONCLUSIONS: Hepatocytes can be transfected with p3MTChins to produce human insulin but may lack the proper glucose-sensing or complex storage and secretion capabilities that allow for a finely tuned dynamic insulin response. Treatment is subtherapeutic, and p3MTChins-hepatocyte function may not endure in an autoimmune model. Without successful preliminary findings, cell therapy involving electroporation of p3MTChins does not appear to be practical as a therapy for diabetes and may not be a strategy to pursue at this time.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/terapia , Terapia Genética , Hepatócitos/transplante , Proinsulina/genética , Animais , Glicemia/metabolismo , Peptídeo C/metabolismo , DNA Complementar/genética , Diabetes Mellitus Experimental/etiologia , Eletroporação , Técnicas de Transferência de Genes , Humanos , Insulina/metabolismo , Fígado , Masculino , Camundongos , Camundongos Endogâmicos NOD , Baço , Estreptozocina , SuínosRESUMO
Use of grafts from donation after circulatory death (DCD) as a strategy to increase the pool of transplantable livers has been limited due to poorer recipient outcomes compared with donation after brain death (DBD). We examined outcomes of recipients of failed DCD grafts who were selected for relisting with regard to waitlist mortality and patient and graft survival after retransplant. From the Scientific Registry of Transplant Recipients database, we identified 1820 adults who underwent first deceased donor liver transplant January 1, 2004 to June 30, 2011, and were relisted due to graft failure; 12.7% were DCD recipients. Compared with DBD recipients, DCD recipients had better waitlist survival (90-day mortality: 8%, DCD recipients; 14-21%, DBD recipients). Of 950 retransplant patients, 14.5% were prior DCD recipients. Graft survival after second liver transplant was similar for prior DCD (28% graft failure within 1 year) and DBD recipients (30%). Patient survival was slightly better for prior DCD (25% death within 1 year) than DBD recipients (28%). Despite higher overall graft failure and morbidity rates, survival of prior DCD recipients who were selected for relisting and retransplant was not worse than survival of DBD recipients.
Assuntos
Rejeição de Enxerto/mortalidade , Hepatopatias/cirurgia , Transplante de Fígado/mortalidade , Complicações Pós-Operatórias , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Adulto , Morte , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/cirurgia , Sobrevivência de Enxerto , Humanos , Hepatopatias/complicações , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reoperação , Fatores de Risco , Taxa de Sobrevida , Listas de EsperaRESUMO
Chronic inflammation may contribute to human immunodeficiency virus (HIV) persistence through a number of potential pathways. We explored the impact of immunosuppressant therapy on peripheral blood measures of HIV persistence following kidney transplantation. Stored plasma and peripheral blood mononuclear cells prior to transplantation and at weeks 12, 26, 52 and 104 posttransplant were obtained from 91 transplant recipients. In a multivariate model, higher pretransplant plasma HIV RNA level (p < 0.0001) and a longer duration of follow-up posttransplant (p = 0.09) were associated with higher posttransplant plasma HIV RNA levels. A higher baseline HIV DNA (p < 0.0001) was significantly associated with higher HIV DNA levels posttransplant, while higher CD4+ T cell count (p = 0.001), sirolimus use (p = 0.04) and a longer duration of follow-up (p = 0.06) were associated with lower posttransplant HIV DNA levels. The association between sirolimus exposure and lower frequency of cells containing HIV DNA levels posttransplant suggest that the immune-modifying drugs may affect the level of HIV persistence during effect therapy. Future studies of sirolimus as a reservoir-modifying agent are warranted.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Infecções por HIV/prevenção & controle , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Feminino , Seguimentos , HIV/genética , HIV/isolamento & purificação , HIV/metabolismo , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/virologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Viral/sangue , Estudos Retrospectivos , Taxa de Sobrevida , TransplantadosRESUMO
Islet transplantation after successful kidney transplantation is a recognized treatment for adults with diabetes and end-stage renal disease (ESRD), but has not been considered an option in the pediatric population. To our knowledge, we report the first combined islet and kidney transplant in a child. The patient was born with bilateral renal hypoplasia and was diagnosed with type 1 diabetes mellitus at age 13 months. He had erratic glycemic control and hypoglycemia unawareness. At 6 years of age, the child safely underwent simultaneous islet and live donor kidney transplantation. Although function of the islet graft was transient, the combined transplant provided significant benefits in terms of glucose control and overall growth and development. Such an approach represents a viable treatment option for pediatric patients with ESRD and unstable diabetes.
Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/cirurgia , Falência Renal Crônica/cirurgia , Transplante de Rim , Transplante de Pâncreas , Adulto , Criança , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Falência Renal Crônica/complicações , Masculino , PrognósticoRESUMO
The Scientific Registry of Transplant Recipients is charged with providing program-specific reports for organ transplant programs in the United States. Monitoring graft survival for pancreas transplant programs has been problematic as there are three different pancreas transplant procedures that may have different outcomes, and analyzing them separately reduces events and statistical power. We combined two consecutive 2.5-year cohorts of transplant recipients to develop Cox proportional hazards models predicting outcomes, and tested these models in the second 2.5-year cohort. We used separate models for 1- and 3-year graft and patient survival for each transplant type: simultaneous pancreas-kidney (SPK), pancreas after kidney (PAK) and pancreas transplant alone (PTA). We first built a predictive model for each pancreas transplant type, and then pooled the transplant types within centers to compare total observed events with total predicted events. Models for 1-year pancreas graft and patient survival yielded C statistics of 0.65 (95% confidence interval, 0.63-0.68) and 0.66 (0.61-0.72), respectively, comparable to C statistics for 1-year patient and graft survival for other organ transplants. Model calibration (Hosmer-Lemeshow method) was also acceptable. We conclude that pooling the results of SPK, PAK and PTA can produce potentially useful models for reporting program-specific pancreas transplant outcomes.
Assuntos
Transplante de Pâncreas/métodos , Transplante de Pâncreas/normas , Sistema de Registros/normas , Obtenção de Tecidos e Órgãos/métodos , Adulto , Algoritmos , Estudos de Coortes , Feminino , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão , Transplante de Rim/métodos , Transplante de Rim/normas , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Transplante de Pâncreas/mortalidade , Pancreatopatias/terapia , Modelos de Riscos Proporcionais , Insuficiência Renal/terapia , Resultado do Tratamento , Estados UnidosRESUMO
Numbers of pancreas transplants have been decreasing over the past decade, but outcomes continue to improve for all types: simultaneous pancreas-kidney transplant, pancreas after kidney transplant (PAK), and pancreas transplant alone (PTA). The most notable decrease occurred for PAK transplants, possibly due in part to decreases in numbers of living donor kidney transplants. The number of new candidates on the pancreas transplant waiting list has decreased steadily since 2000; only 1005 active candidates were added in 2011. Transplant rates for all pancreas transplant types reached a low in 2011 of 34.9 transplants per 100 wait-list years. Deceased donation rates have also been decreasing since 2005, but use of donation after circulatory death has been gradually increasing. The discard rate in 2011 was 27.7%, and higher for pancreata recovered from older donors. Improved outcomes during the early posttransplant period largely reflect improved donor and recipient selection and improved technical strategies. Inconsistent definitions of graft failure across reporting centers creates an ongoing challenge in the interpretation of outcome data for pancreas transplants. Rates of posttransplant re-hospitalization are high, most occurring in the first 6 months. Rejection rates are highest for PTA recipients, who also experience higher incidence of posttransplant lymphoproliferative disorder.