RESUMO
Patients waitlisted for and recipients of solid organ transplants (SOT) are perceived to have a higher risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and death; however, definitive epidemiological evidence is lacking. In a comprehensive national cohort study enabled by linkage of the UK transplant registry and Public Health England and NHS Digital Tracing services, we examined the incidence of laboratory-confirmed SARS-CoV-2 infection and subsequent mortality in patients on the active waiting list for a deceased donor SOT and recipients with a functioning SOT as of February 1, 2020 with follow-up to May 20, 2020. Univariate and multivariable techniques were used to compare differences between groups and to control for case-mix. One hundred ninety-seven (3.8%) of the 5184 waitlisted patients and 597 (1.3%) of the 46 789 SOT recipients tested positive for SARS-CoV-2. Mortality after testing positive for SARS-CoV-2 was 10.2% (20/197) for waitlisted patients and 25.8% (154/597) for SOT recipients. Increasing recipient age was the only variable independently associated with death after positive SARS-CoV-2 test. Of the 1004 transplants performed in 2020, 41 (4.1%) recipients have tested positive for SARS-CoV-2 with 8 (0.8%) deaths reported by May 20. These data provide evidence to support decisions on the risks and benefits of SOT during the coronavirus disease 2019 pandemic.
Assuntos
COVID-19/epidemiologia , Transplante de Órgãos , Pandemias , Sistema de Registros , SARS-CoV-2 , Doadores de Tecidos , Transplantados , Adolescente , Adulto , Criança , Pré-Escolar , Inglaterra/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Listas de Espera/mortalidade , Adulto JovemRESUMO
Worldwide, the number of patients able to benefit from kidney transplantation is greatly restricted by the severe shortage of deceased donor organs. Allocation of this scarce resource is increasingly challenging and complex. Striking an acceptable balance between efficient use of (utility) and fair access to (equity) the limited supply of donated kidneys raises controversial but important debates at ethical, medical, and social levels. There is no international consensus on the recipient and donor factors that should be considered in the kidney allocation process. There is a general trend toward a reduction in the influence of human leukocyte antigen mismatch and an increase in the importance of other factors shown to affect posttransplant outcomes, such as cold ischemia, duration of dialysis, donor and recipient age, and comorbidity. Increased consideration of equity has led to improved access to transplantation for disadvantaged patient groups. There has been an overall improvement in the transparency and accountability of allocation policies. Novel and contentious approaches in kidney allocation include the use of survival prediction scores as a criterion for accessing the waiting list and at the point of organ offering with matching of predicted graft and recipient survival. This review compares the diverse international approaches to deceased donor kidney allocation and their evolution over the last decade.
Assuntos
Seleção do Doador/tendências , Saúde Global/tendências , Acessibilidade aos Serviços de Saúde/tendências , Transplante de Rim/tendências , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/tendências , Difusão de Inovações , Seleção do Doador/legislação & jurisprudência , Saúde Global/legislação & jurisprudência , Equidade em Saúde/tendências , Política de Saúde/tendências , Acessibilidade aos Serviços de Saúde/legislação & jurisprudência , Disparidades em Assistência à Saúde/tendências , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/legislação & jurisprudência , Formulação de Políticas , Fatores de Tempo , Doadores de Tecidos/legislação & jurisprudência , Obtenção de Tecidos e Órgãos/legislação & jurisprudênciaRESUMO
BACKGROUND: Living donor kidney transplantation (LDKT) provides more timely access to transplantation and better clinical outcomes than deceased donor kidney transplantation (DDKT). This study investigated disparities in the utilization of LDKT in the UK. METHODS: A total of 2055 adults undergoing kidney transplantation between November 2011 and March 2013 were prospectively recruited from all 23 UK transplant centres as part of the Access to Transplantation and Transplant Outcome Measures (ATTOM) study. Recipient variables independently associated with receipt of LDKT versus DDKT were identified. RESULTS: Of the 2055 patients, 807 (39.3%) received LDKT and 1248 (60.7%) received DDKT. Multivariable modelling demonstrated a significant reduction in the likelihood of LDKT for older age {odds ratio [OR] 0.11 [95% confidence interval (CI) 0.08-0.17], P < 0.0001 for 65-75 years versus 18-34 years}; Asian ethnicity [OR 0.55 (95% CI 0.39-0.77), P = 0.0006 versus White]; Black ethnicity [OR 0.64 (95% CI 0.42-0.99), P = 0.047 versus White]; divorced, separated or widowed [OR 0.63 (95% CI 0.46-0.88), P = 0.030 versus married]; no qualifications [OR 0.55 (95% CI 0.42-0.74), P < 0.0001 versus higher education qualifications]; no car ownership [OR 0.51 (95% CI 0.37-0.72), P = 0.0001] and no home ownership [OR 0.65 (95% CI 0.85-0.79), P = 0.002]. The odds of LDKT varied significantly between countries in the UK. CONCLUSIONS: Among patients undergoing kidney transplantation in the UK, there are significant age, ethnic, socio-economic and geographic disparities in the utilization of LDKT. Further work is needed to explore the potential for targeted interventions to improve equity in living donor transplantation.
Assuntos
Seleção do Doador , Conhecimentos, Atitudes e Prática em Saúde , Transplante de Rim , Doadores Vivos , Obtenção de Tecidos e Órgãos , Adolescente , Adulto , Negro ou Afro-Americano , Idoso , Barreiras de Comunicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reino Unido , População Branca , Adulto JovemRESUMO
OBJECTIVES: To report health-state utility values measured using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) in a large sample of patients with end-stage renal disease and to explore how these values vary in relation to patient characteristics and treatment factors. METHODS: As part of the prospective observational study entitled "Access to Transplantation and Transplant Outcome Measures," we captured information on patient characteristics and treatment factors in a cohort of incident kidney transplant recipients and a cohort of prevalent patients on the transplant waiting list in the United Kingdom. We assessed patients' health status using the EQ-5D-5L and conducted multivariable regression analyses of index scores. RESULTS: EQ-5D-5L responses were available for 512 transplant recipients and 1704 waiting-list patients. Mean index scores were higher in transplant recipients at 6 months after transplant surgery (0.83) compared with patients on the waiting list (0.77). In combined regression analyses, a primary renal diagnosis of diabetes was associated with the largest decrement in utility scores. When separate regression models were fitted to each cohort, female gender and Asian ethnicity were associated with lower utility scores among waiting-list patients but not among transplant recipients. Among waiting-list patients, longer time spent on dialysis was also associated with poorer utility scores. When comorbidities were included, the presence of mental illness resulted in a utility decrement of 0.12 in both cohorts. CONCLUSIONS: This study provides new insights into variations in health-state utility values from a single source that can be used to inform cost-effectiveness evaluations in patients with end-stage renal disease.
Assuntos
Nível de Saúde , Falência Renal Crônica/cirurgia , Transplante de Rim , Avaliação de Resultados em Cuidados de Saúde/métodos , Qualidade de Vida , Adolescente , Adulto , Feminino , Humanos , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Diálise Renal/métodos , Fatores de Tempo , Transplantados/estatística & dados numéricos , Reino Unido , Listas de Espera , Adulto JovemRESUMO
BACKGROUND: The influence of donor and recipient factors on outcomes following kidney transplantation is commonly analysed using Cox regression models, but this approach is not useful for predicting long-term survival beyond observed data. We demonstrate the application of a flexible parametric approach to fit a model that can be extrapolated for the purpose of predicting mean patient survival. The primary motivation for this analysis is to develop a predictive model to estimate post-transplant survival based on individual patient characteristics to inform the design of alternative approaches to allocating deceased donor kidneys to those on the transplant waiting list in the United Kingdom. METHODS: We analysed data from over 12,000 recipients of deceased donor kidney or combined kidney and pancreas transplants between 2003 and 2012. We fitted a flexible parametric model incorporating restricted cubic splines to characterise the baseline hazard function and explored a range of covariates including recipient, donor and transplant-related factors. RESULTS: Multivariable analysis showed the risk of death increased with recipient and donor age, diabetic nephropathy as the recipient's primary renal diagnosis and donor hypertension. The risk of death was lower in female recipients, patients with polycystic kidney disease and recipients of pre-emptive transplants. The final model was used to extrapolate survival curves in order to calculate mean survival times for patients with specific characteristics. CONCLUSION: The use of flexible parametric modelling techniques allowed us to address some of the limitations of both the Cox regression approach and of standard parametric models when the goal is to predict long-term survival.
Assuntos
Transplante de Rim/mortalidade , Modelos Estatísticos , Seleção de Pacientes , Insuficiência Renal Crônica/cirurgia , Adolescente , Adulto , Fatores Etários , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/epidemiologia , Seleção do Doador , Feminino , Previsões/métodos , Humanos , Hipertensão/epidemiologia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doenças Renais Policísticas/complicações , Doenças Renais Policísticas/epidemiologia , Período Pós-Operatório , Insuficiência Renal Crônica/etiologia , Alocação de Recursos , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: In a number of countries, reimbursement to hospitals providing renal dialysis services is set according to a fixed tariff. While the cost of maintenance dialysis and transplant surgery are amenable to a system of fixed tariffs, patients with established renal failure commonly present with comorbid conditions that can lead to variations in the need for hospitalization beyond the provision of renal replacement therapy. METHODS: Patient-level cost data for incident renal replacement therapy patients in England were obtained as a result of linkage of the Hospital Episodes Statistics dataset to UK Renal Registry data. Regression models were developed to explore variations in hospital costs in relation to treatment modality, number of years on treatment and factors such as age and comorbidities. The final models were then used to predict annual costs for patients with different sets of characteristics. RESULTS: Excluding the cost of renal replacement therapy itself, inpatient costs generally decreased with number of years on treatment for haemodialysis and transplant patients, whereas costs for patients receiving peritoneal dialysis remained constant. Diabetes was associated with higher mean annual costs for all patients irrespective of treatment modality and hospital setting. Age did not have a consistent effect on costs. CONCLUSIONS: Combining predicted hospital costs with the fixed costs of renal replacement therapy showed that the total cost differential for a patient continuing on dialysis rather than receiving a transplant is considerable following the first year of renal replacement therapy, thus reinforcing the longer-term economic advantage of transplantation over dialysis for the health service.
Assuntos
Custos de Cuidados de Saúde , Hospitalização/economia , Falência Renal Crônica/economia , Terapia de Substituição Renal/economia , Idoso , Comorbidade , Diabetes Mellitus , Inglaterra , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/economia , Sistema de Registros , Diálise Renal/estatística & dados numéricosRESUMO
BACKGROUND: There is variation in time to listing and rates of listing for transplantation between renal units in the UK. While research has mainly focused on healthcare organization, little is known about patient perspectives of entry onto the transplant waiting list. This qualitative study aimed to explore patients' views and experiences of kidney transplant listing. METHODS: Semi-structured interviews were conducted with patients aged under 75, who were on dialysis and on the transplant waiting list, not on the waiting list, undergoing assessment for listing or who had received a transplant. Patients were recruited from a purposive sample of nine UK renal units, which included transplanting and non-transplanting units and units with high and low wait-listing patterns. Interviews were transcribed verbatim and analysed using thematic analysis. RESULTS: Fifty-three patients (5-7 per renal unit) were interviewed. Patients reported that they had received little information about the listing process. Some patients did not know if they were listed or had found they were not listed when they had thought they were on the list. Others expressed distress when they felt they had been excluded from potential listing based on age and/or comorbidity and felt the process was unfair. Many patients were not aware of pre-emptive transplantation and believed they had to be on dialysis before being able to be listed. There was some indication that pre-emptive transplantation was discussed more often in transplant than non-transplant units. Lastly, some patients were reluctant to consider family members as potential donors as they reported they would feel 'guilty' if the donor suffered subsequent negative effects. CONCLUSIONS: Findings suggest a need to review current practice to further understand individual and organizational reasons for the renal unit variation identified in patient understanding of transplant listing. The communication of information warrants attention to ensure patients are fully informed about the listing process and opportunity for pre-emptive transplantation in a way that is meaningful and understandable to them.
Assuntos
Atitude Frente a Saúde , Falência Renal Crônica/cirurgia , Transplante de Rim/psicologia , Relações Médico-Paciente , Listas de Espera , Adulto , Idoso , Feminino , Humanos , Falência Renal Crônica/psicologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Reino Unido , Adulto JovemRESUMO
Importance: Cancer transmission is a known risk for recipients of organ transplants. Many people wait a long time for a suitable transplant; some never receive one. Although patients with brain tumors may donate their organs, opinions vary on the risks involved. Objective: To determine the risk of cancer transmission associated with organ transplants from deceased donors with primary brain tumors. Key secondary objectives were to investigate the association that donor brain tumors have with organ usage and posttransplant survival. Design, Setting, and Participants: This was a cohort study in England and Scotland, conducted from January 1, 2000, to December 31, 2016, with follow-up to December 31, 2020. This study used linked data on deceased donors and solid organ transplant recipients with valid national patient identifier numbers from the UK Transplant Registry, the National Cancer Registration and Analysis Service (England), and the Scottish Cancer Registry. For secondary analyses, comparators were matched on factors that may influence the likelihood of organ usage or transplant failure. Statistical analysis of study data took place from October 1, 2021, to May 31, 2022. Exposures: A history of primary brain tumor in the organ donor, identified from all 3 data sources using disease codes. Main Outcomes and Measures: Transmission of brain tumor from the organ donor into the transplant recipient. Secondary outcomes were organ utilization (ie, transplant of an offered organ) and survival of kidney, liver, heart, and lung transplants and their recipients. Key covariates in donors with brain tumors were tumor grade and treatment history. Results: This study included a total of 282 donors (median [IQR] age, 42 [33-54] years; 154 females [55%]) with primary brain tumors and 887 transplants from them, 778 (88%) of which were analyzed for the primary outcome. There were 262 transplants from donors with high-grade tumors and 494 from donors with prior neurosurgical intervention or radiotherapy. Median (IQR) recipient age was 48 (35-58) years, and 476 (61%) were male. Among 83 posttransplant malignancies (excluding NMSC) that occurred over a median (IQR) of 6 (3-9) years in 79 recipients of transplants from donors with brain tumors, none were of a histological type matching the donor brain tumor. Transplant survival was equivalent to that of matched controls. Kidney, liver, and lung utilization were lower in donors with high-grade brain tumors compared with matched controls. Conclusions and Relevance: Results of this cohort study suggest that the risk of cancer transmission in transplants from deceased donors with primary brain tumors was lower than previously thought, even in the context of donors that are considered as higher risk. Long-term transplant outcomes are favorable. These results suggest that it may be possible to safely expand organ usage from this donor group.
Assuntos
Neoplasias Encefálicas , Transplante de Rim , Transplante de Órgãos , Feminino , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Estudos de Coortes , Doadores de Tecidos , Transplante de Órgãos/efeitos adversos , Neoplasias Encefálicas/epidemiologiaRESUMO
The coronavirus disease 2019 (COVID-19) pandemic has had a major global impact on solid organ transplantation (SOT). An estimated 16% global reduction in transplant activity occurred over the course of 2020, most markedly impacting kidney transplant and living donor programs, resulting in substantial knock-on effects for waitlisted patients. The increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk and excess deaths in transplant candidates has resulted in substantial effort to prioritize the safe restart and continuation of transplant programs over the second year of the pandemic, with transplant rates returning towards prepandemic levels. Over the past 2 y, COVID-19 mortality in SOT recipients has fallen from 20%-25% to 8%-10%, attributed to the increased and early availability of SARS-CoV-2 testing, adherence to nonpharmaceutical interventions, development of novel treatments, and vaccination. Despite these positive steps, transplant programs and SOT recipients continue to face challenges. Vaccine efficacy in SOT recipients is substantially lower than the general population and SOT recipients remain at an increased risk of adverse outcomes if they develop COVID-19. SOT recipients and transplant teams need to remain vigilant and ongoing adherence to nonpharmaceutical interventions appears essential. In this review, we summarize the global impact of COVID-19 on transplant activity, donor evaluation, and patient outcomes over the past 2 y, discuss the current strategies aimed at preventing and treating SARS-CoV-2 infection in SOT recipients, and based on lessons learnt from this pandemic, propose steps the transplant community could consider as preparation for future pandemics.
Assuntos
COVID-19 , Transplante de Órgãos , COVID-19/epidemiologia , Teste para COVID-19 , Humanos , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/métodos , Pandemias/prevenção & controle , SARS-CoV-2 , TransplantadosRESUMO
BACKGROUND: The clinical effectiveness of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunosuppressed solid organ and islet transplant (SOT) recipients is unclear. METHODS: We linked 4 national registries to retrospectively identify laboratory-confirmed SARS-CoV-2 infections and deaths within 28 d in England between September 1, 2020, and August 31, 2021, comparing unvaccinated adult SOT recipients and those who had received 2 doses of ChAdOx1-S or BNT162b2 vaccine. Infection incidence rate ratios were adjusted for recipient demographics and calendar month using a negative binomial regression model, with 95% confidence intervals. Case fatality rate ratios were adjusted using a Cox proportional hazards model to generate hazard ratio (95% confidence interval). RESULTS: On August 31, 2021, it was found that 3080 (7.1%) were unvaccinated, 1141 (2.6%) had 1 vaccine dose, and 39 260 (90.3%) had 2 vaccine doses. There were 4147 SARS-CoV-2 infections and 407 deaths (unadjusted case fatality rate 9.8%). The risk-adjusted infection incidence rate ratio was 1.29 (1.03-1.61), implying that vaccination was not associated with reduction in risk of testing positive for SARS-CoV-2 RNA. Overall, the hazard ratio for death within 28 d of SARS-CoV-2 infection was 0.80 (0.63-1.00), a 20% reduction in risk of death in vaccinated patients (P = 0.05). Two doses of ChAdOx1-S were associated with a significantly reduced risk of death (hazard ratio, 0.69; 0.52-0.92), whereas vaccination with BNT162b2 was not (0.97; 0.71-1.31). CONCLUSIONS: Vaccination of SOT recipients confers some protection against SARS-CoV-2-related mortality, but this protection is inferior to that achieved in the general population. SOT recipients require additional protective measures, including further vaccine doses, antiviral drugs, and nonpharmaceutical interventions.
Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Humanos , RNA Viral , Estudos Retrospectivos , TransplantadosRESUMO
OBJECTIVE: To examine quality of life (QoL) and other patient-reported outcome measures (PROMs) in kidney transplant recipients and those awaiting transplantation. DESIGN: Longitudinal cohort questionnaire surveys and qualitative semi-structured interviews using thematic analysis with a pragmatic approach. SETTING: Completion of generic and disease-specific PROMs at two time points, and telephone interviews with participants UK-wide. PARTICIPANTS: 101 incident deceased-donor (DD) and 94 incident living-donor (LD) kidney transplant recipients, together with 165 patients on the waiting list (WL) from 18 UK centres recruited to the Access to Transplantation and Transplant Outcome Measures (ATTOM) programme completed PROMs at recruitment (November 2011 to March 2013) and 1 year follow-up. Forty-one of the 165 patients on the WL received a DD transplant and 26 received a LD transplant during the study period, completing PROMs initially as patients on the WL, and again 1 year post-transplant. A subsample of 10 LD and 10 DD recipients participated in qualitative semi-structured interviews. RESULTS: LD recipients were younger, had more educational qualifications and more often received a transplant before dialysis. Controlling for these and other factors, cross-sectional analyses at 12 months post-transplant suggested better QoL, renal-dependent QoL and treatment satisfaction for LD than DD recipients. Patients on the WL reported worse outcomes compared with both transplant groups. However, longitudinal analyses (controlling for pre-transplant differences) showed that LD and DD recipients reported similarly improved health status and renal-dependent QoL (p<0.01) pre-transplant to post-transplant. Patients on the WL had worsened health status but no change in QoL. Qualitative analyses revealed transplant recipients' expectations influenced their recovery and satisfaction with transplant. CONCLUSIONS: While cross-sectional analyses suggested LD kidney transplantation leads to better QoL and treatment satisfaction, longitudinal assessment showed similar QoL improvements in PROMs for both transplant groups, with better outcomes than for those still wait-listed. Regardless of transplant type, clinicians need to be aware that managing expectations is important for facilitating patients' adjustment post-transplant.
Assuntos
Transplante de Rim , Qualidade de Vida , Estudos Transversais , Humanos , Doadores Vivos , Medidas de Resultados Relatados pelo Paciente , Diálise Renal , Inquéritos e Questionários , Reino UnidoRESUMO
BACKGROUND: The number of patients waiting to receive a kidney transplant outstrips the supply of donor organs. We sought to quantify trade-offs associated with different approaches to deceased donor kidney allocation in terms of quality-adjusted life years (QALYs), costs, and access to transplantation. METHODS: An individual patient simulation model was developed to compare 5 different approaches to kidney allocation, including the 2006 UK National Kidney Allocation Scheme (NKAS) and a QALY maximization approach designed to maximize health gains from a limited supply of donor organs. We used various sources of patient-level data to develop multivariable regression models to predict survival, health state utilities, and costs. We simulated the allocation of kidneys from 2200 deceased donors to a waiting list of 5500 patients and produced estimates of total lifetime costs and QALYs for each allocation scheme. RESULTS: Among patients who received a transplant, the QALY maximization approach generated 48 045 QALYs and cost £681 million, while the 2006 NKAS generated 44 040 QALYs and cost £625 million. When also taking into consideration outcomes for patients who were not prioritized to receive a transplant, the 2006 NKAS produced higher total QALYs and costs and an incremental cost-effectiveness ratio of £110 741/QALY compared with the QALY maximization approach. CONCLUSIONS: Compared with the 2006 NKAS, a QALY maximization approach makes more efficient use of deceased donor kidneys but reduces access to transplantation for older patients and results in greater inequity in the distribution of health gains between patients who receive a transplant and patients who remain on the waiting list.
Assuntos
Simulação por Computador , Seleção do Doador , Alocação de Recursos para a Atenção à Saúde , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Transplante de Rim , Doadores de Tecidos/provisão & distribuição , Listas de Espera , Adolescente , Adulto , Fatores Etários , Análise Custo-Benefício , Seleção do Doador/economia , Feminino , Custos de Cuidados de Saúde , Alocação de Recursos para a Atenção à Saúde/economia , Acessibilidade aos Serviços de Saúde/economia , Nível de Saúde , Disparidades em Assistência à Saúde/economia , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/economia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Formulação de Políticas , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Listas de Espera/mortalidade , Adulto JovemRESUMO
BACKGROUND: Comorbidity is increasingly common in kidney transplant recipients, yet the implications for transplant outcomes are not fully understood. We analyzed the relationship between recipient comorbidity and survival outcomes in a UK-wide prospective cohort study-Access to Transplantation and Transplant Outcome Measures (ATTOM). METHODS: A total of 2100 adult kidney transplant recipients were recruited from all 23 UK transplant centers between 2011 and 2013. Data on 15 comorbidities were collected at the time of transplantation. Multivariable Cox regression models were used to analyze the relationship between comorbidity and 2-year graft survival, patient survival, and transplant survival (earliest of graft failure or patient death) for deceased-donor kidney transplant (DDKT) recipients (n = 1288) and living-donor kidney transplant (LDKT) recipients (n = 812). RESULTS: For DDKT recipients, peripheral vascular disease (hazard ratio [HR] 3.04, 95% confidence interval [CI]: 1.37-6.74; P = 0.006) and obesity (HR 2.27, 95% CI: 1.27-4.06; P = 0.006) were independent risk factors for graft loss, while heart failure (HR 3.77, 95% CI: 1.79-7.95; P = 0.0005), cerebrovascular disease (HR 3.45, 95% CI: 1.72-6.92; P = 0.0005), and chronic liver disease (HR 4.36, 95% CI: 1.29-14.71; P = 0.018) were associated with an increased risk of mortality. For LDKT recipients, heart failure (HR 3.83, 95% CI: 1.15-12.81; P = 0.029) and diabetes (HR 2.23, 95% CI: 1.03-4.81; P = 0.042) were associated with poorer transplant survival. CONCLUSIONS: The key comorbidities that predict poorer 2-year survival outcomes after kidney transplantation have been identified in this large prospective cohort study. The findings will facilitate assessment of individual patient risks and evidence-based decision making.
Assuntos
Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Transplantados/estatística & dados numéricos , Adolescente , Adulto , Idoso , Transtornos Cerebrovasculares/epidemiologia , Doença Crônica/epidemiologia , Comorbidade , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Falência Renal Crônica/mortalidade , Hepatopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Doenças Vasculares Periféricas/epidemiologia , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Reino Unido/epidemiologia , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Despite the presence of a universal health care system, it is unclear if there is intercenter variation in access to kidney transplantation in the United Kingdom. This study aims to assess whether equity exists in access to kidney transplantation in the United Kingdom after adjustment for patient-specific factors and center practice patterns. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this prospective, observational cohort study including all 71 United Kingdom kidney centers, incident RRT patients recruited between November 2011 and March 2013 as part of the Access to Transplantation and Transplant Outcome Measures study were analyzed to assess preemptive listing (n=2676) and listing within 2 years of starting dialysis (n=1970) by center. RESULTS: Seven hundred and six participants (26%) were listed preemptively, whereas 585 (30%) were listed within 2 years of commencing dialysis. The interquartile range across centers was 6%-33% for preemptive listing and 25%-40% for listing after starting dialysis. Patient factors, including increasing age, most comorbidities, body mass index >35 kg/m2, and lower socioeconomic status, were associated with a lower likelihood of being listed and accounted for 89% and 97% of measured intercenter variation for preemptive listing and listing within 2 years of starting dialysis, respectively. Asian (odds ratio, 0.49; 95% confidence interval, 0.33 to 0.72) and Black (odds ratio, 0.43; 95% confidence interval, 0.26 to 0.71) participants were both associated with reduced access to preemptive listing; however Asian participants were associated with a higher likelihood of being listed after starting dialysis (odds ratio, 1.42; 95% confidence interval, 1.12 to 1.79). As for center factors, being registered at a transplanting center (odds ratio, 3.1; 95% confidence interval, 2.36 to 4.07) and a universal approach to discussing transplantation (odds ratio, 1.4; 95% confidence interval, 1.08 to 1.78) were associated with higher preemptive listing, whereas using a written protocol was associated negatively with listing within 2 years of starting dialysis (odds ratio, 0.7; 95% confidence interval, 0.58 to 0.9). CONCLUSIONS: Patient case mix accounts for most of the intercenter variation seen in access to transplantation in the United Kingdom, with practice patterns also contributing some variation. Socioeconomic inequity exists despite having a universal health care system.
Assuntos
Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Falência Renal Crônica/terapia , Transplante de Rim/estatística & dados numéricos , Listas de Espera , Adolescente , Adulto , Fatores Etários , Idoso , Povo Asiático/estatística & dados numéricos , População Negra/estatística & dados numéricos , Índice de Massa Corporal , Comorbidade , Feminino , Disparidades em Assistência à Saúde/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Estudos Prospectivos , Diálise Renal , Classe Social , Reino Unido , Adulto JovemRESUMO
This review article focuses on current clinical outcomes with novel perfusion strategies in organ transplantation. Broadly, these approaches can be divided into in situ regional perfusion in the donor and ex situ machine perfusion of individual organs. In both settings, hypothermic and normothermic techniques are in clinical use. Evidence from full text articles, abstracts, and data presented at scientific meetings has been considered. Animal studies have been excluded. The review focuses on kidney, liver, pancreas, heart, and lungs. The level of evidence ranges from quasi-experimental work in human pancreas to multiple meta-analyses of Randomized Controlled Trials for hypothermic machine perfusion of kidneys. The data in this review were presented to experts in organ perfusion and preservation at the National Health Service Blood and Transplant Preservation and Perfusion Future Strategy Summit in London in October 2018. The outcomes of the meeting are discussed in the review after due consideration of the available evidence base.
Assuntos
Preservação de Órgãos/métodos , Transplante de Órgãos/métodos , Perfusão/métodos , HumanosRESUMO
BACKGROUND: To investigate whether there are any variations in the evaluation of adult candidates for cadaveric renal transplantation among transplant centers in the United Kingdom. METHODS: An online survey of transplant units in the United Kingdom, including nephrologists, surgeons, and transplant coordinators, measured differences in the assessment process and evaluation of patient's age, body mass index (BMI), cardiovascular comorbidity, and viral serology. RESULTS: A response was received from 20 out of the 23 centers (87%). These centers perform 90% of all renal transplants in the United Kingdom. In 30% of the units, there is no formal transplant assessment clinic. There is no cutoff age limit for assessment across the United Kingdom, but 12 centers (60%) exclude patients with a high BMI, with a median cutoff BMI of 35. Eight out of the 20 centers do not give cytomegalovirus (CMV)-negative patients the option to receive kidneys from a CMV-positive donor. Hepatitis C antibody-positive donors are not used in 50% of the units. There is considerable variation in the investigation of cardiovascular disease and exclusion criteria based on cardiovascular status of the patients. Five units have no consistent policy of re-evaluating patients once they are listed. CONCLUSIONS: There is evidence, from this study, of significant variations in the assessment of patients for renal transplantation across the United Kingdom. Further research and better-defined guidelines are required for a uniform assessment process and to ensure equity of access to the renal transplant waiting list.
Assuntos
Transplante de Rim , Avaliação de Resultados em Cuidados de Saúde , Índice de Massa Corporal , Sistema Cardiovascular , Trato Gastrointestinal , Humanos , Sorologia , Reino Unido , Listas de EsperaRESUMO
The Sonic hedgehog (Shh) signalling pathway plays an important role in developmental patterning and proliferation. Recent evidence suggests that Shh also plays a role in the development of the immune system. Here, we demonstrate that components of the Shh signalling pathway are expressed in human macrophages and that the receptor for Shh, Ptc, is up-regulated by a commercially available recombinant preparation of Shh (CArShh). Further, we report that the addition of CArShh up-regulates the production of IL-6, IL-8, MCP-1, IP-10, MIG and RANTES by macrophages, an effect enhanced by the presence of fetal calf serum in the culture medium. In contrast, TGF-beta, TNF-alpha, IL-1b, IL-12 and IL-10 production were not modulated by CArShh and VEGF was minimally up-regulated even in the presence of serum. The up-regulation of these cytokines and chemokines was abrogated by CD14 inhibition and polymixin B, but not reliably inhibited by the specific Shh pathway inhibitor cyclopamine. These results suggest that, although components of the Shh signalling pathway are expressed in macrophages, the modulation of macrophage cytokine and chemokine effector function seen in response to commercially available rShh results from low levels of endotoxin contained within the CArShh preparations employed to explore the effects of Shh in vitro.
Assuntos
Citocinas/metabolismo , Endotoxinas/análise , Proteínas Hedgehog/metabolismo , Macrófagos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Contaminação de Medicamentos , Proteínas Hedgehog/farmacologia , Humanos , Receptores de Lipopolissacarídeos/metabolismo , Receptores Patched , Polimixina B/farmacologia , Receptores de Superfície Celular/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Transdução de Sinais , Regulação para Cima , Alcaloides de Veratrum/farmacologiaRESUMO
BACKGROUND: Despite the availability of guidelines for the evaluation of candidates for renal transplantation, variation in access to transplantation exists. This national survey investigates whether center variation exists in the assessment of patients for renal transplantation in the United Kingdom. METHODS: An online survey, informed by qualitative interviews, was distributed to all UK renal centers. This survey examined center approaches to chronic kidney disease service provision, transplant recipient assessment, education provision, and waitlisting decision making processes. Center reevaluation policies for patients already listed and priorities for future development were also examined. RESULTS: All 71 renal centers responded. Of these, 83% reviewed predialysis patients in a low clearance clinic. In 26% of the centers, transplantation was not discussed as a treatment option with all patients. Fourteen centers reported having a dedicated transplant assessment clinic, whereas 28% did not have a formal assessment protocol. Age was an exclusion criterion for listing in 3 centers, all of which had a cutoff at 75 years. Eighty-three percent of the centers excluded patients with a high body mass index. Cardiac investigations were risk-stratified in 90% of centers. Surgical involvement varied with 11% of centers listing patients without formal surgical review. There was no formal protocol in place to reevaluate listed patients in 62% of centers. CONCLUSIONS: There is wide variation in UK practice patterns for listing patients for renal transplantation, though its impact on access to transplantation is unclear. The extent to which center-specific and patient-specific factors affect access to transplantation requires further analysis in a prospective cohort of patients.