Evolution of renal transplantation activity in Portugal: public data from 2003 to 2015

Para doentes insuficientes renais, o transplante de rim, quando possível, é a terapia de substituição da função renal que garante uma menor mortalidade, a redução de problemas cardiovasculares e uma melhor qualidade de vida em comparação com a diálise, mesmo em doentes com idade avançada e com morbilidades. A análise sistemática de indicadores associados à actividade da transplantação renal permite a melhor caracterização e conhecimento dos problemas existentes. O objectivo deste trabalho é o de descrever a evolução da actividade de transplantação renal em Portugal com a informação de acesso livre que está disponível para análise. Este estudo tem por base a informação do Observatório Global em Doação e Transplantação, recolhida e produzida pela colaboração entre a Organização Mundial de Saúde e a Organización Nacional de Trasplantes, de onde recolhemos os dados disponíveis respeitantes a Portugal, para os anos entre 2003 e 2015. No período em análise verificamos que 2009 foi o ano que registou um maior número de transplantes renais. Em 2012 registou- se a maior queda do número de transplantes de rim com dador cadáver (-20.8%) em relação ao ano predecessor. Só com a disponibilização de dados para análise é possível fazer o melhor escrutínio de políticas a implementar.For patients with renal insufficiency, renal transplantation, when possible, is the renal replacement therapy that guarantees a lower mortality, a reduction of cardiovascular problems, and a better quality of life compared to dialysis; even in patients with advanced age and morbidities. The systematic analysis of indicators associated with renal transplantation activity allows a better characterization and understanding of inherent problems. The objective of this study is to describe the evolution of kidney transplant activity in Portugal with free access information that is available for analysis. This study is based on information from the Global Observatory on Donation and Transplantation, collected and produced by the collaboration between the World Health Organization and the Organización Nacional de Trasplantes, from where we collected the available data regarding to Portugal for the years between 2003 and 2015. In the analyzed period, 2009 was the year with a higher number of kidney transplants. In 2012 it was registered the highest reduction in kidney transplants from cadaveric donors (-20.8%) compared to the predecessor year.info:eu-repo/semantics/publishedVersio

Transforming Growth Factor-b1 polymorphism is not associated with chronic graft disease: evidence from a meta-analysis

Kidney transplantation has been recognised as the optimal treatment choice for most end stage renal disease patients and the increase of allograft survival rates is achieved through the refinement of novel immunosuppressive agents. Chronic Graft Disease (CGD) is a multifactorial process that likely includes a combination of immunological, apoptotic and inflammatory factors. The application of individualised immunosuppressive therapies will also depend on the identification of risk factors that can influence chronic disease. Despite being the subject of several independent studies, investigations of the relationship between transforming growth factor-b1 (TGF-b1) polymorphisms and kidney graft outcome continue to be plagued by contradictory conclusions

Assessment of a Portuguese panel reactive antibody calculator

Calculated panel-reactive antibody (cPRA) is an accurate measure for the definition of candidates’ immunization to a transplant. Based upon unacceptable HLA antigens to which the patient has been sensitized, cPRA is computed with HLA allelic and haplotypic frequencies from a pool of possible donors and represents the percentage of donors that express one or more of the antigens unacceptable for a given transplant candidate. The aim of this study is to compare cPRA values obtained from HLA frequencies of Portuguese donors with values obtained from cPRA calculators from international established sources.info:eu-repo/semantics/publishedVersio

Virtual crossmatch and calculated panel reactive antibody: two sides of the same coin

Background: The demand for kidneys for transplantation grows daily due to the successful treatment of many patients with end stage renal disease. The success of kidney transplants depends largely on genetic and immunological compatibility between the organ and its recipient. An important barrier to kidney transplantation is the sensitization of transplant candidates to human leukocyte antigen (HLA)

HLA-A, -C, -B, and -DRB1 allelic and haplotypic diversity in bone marrow volunteer donors from Northern Portugal

Analysis of the HLA allelic and haplotype frequency data in different populations helps to shed light on the evolutionary factors that result in genetic polymorphism and the biological relationships among different ethnic groups. It is important to analyse HLA allele and haplotype frequencies in different populations to find compatible marrow transplantation donors from unrelated individuals. The aim of this study was to investigate the distribution of HLA-A, -C, -B and DRB1 alleles and haplotypes in Northern Portugal. The HLA-A, -C, -B, and -DRB1 allele frequencies were determined by direct counting. The haplotype frequencies were calculated using the expectation-maximisation algorithm in Arlequin v3 software. The Hardy-Weinberg equilibrium was verified using the Guo and Thompson method. The most frequent (> 10%) HLA-A alleles (A*02, A*01, A*03, and A*24), HLA-B alleles (B*44, and B*35) and HLA-C alleles (C*07, and C*04) found in this study frequently occur in many other Caucasian populations. Of the class II HLA alleles at the HLA-DRB1* locus, the allelic groups HLA-DRB1*07 and -DRB1*13 occur most frequently (> 15%) in the Portuguese population, as previously reported by others. The HLA-A*01-C*07-B*08-DRB1*03 and HLA-A*29-C*16-B*44-DRB1*07 haplotypes, described as being of Pan European and western European origin, respectively, were the most frequent haplotypes found in our sample, and they are very frequent in Caucasian Brazilian, German, Italian, Spanish and the previously described Portuguese populations. These data represent an important contribution to future anthropological and disease association studies involving the Portuguese population

Evaluation of the Portuguese kidney transplant allocation system: comparative results from a simulation

The distribution of such a scarce resource as deceased donor kidneys should be made by observing a balance between fairness, efficiency and flexibility. Before implementing a new kidney allocation system, these principles should be evaluated and assured objectively. In this article we compare the renal transplant donor-recipient pair selection system implemented in Portugal in 2007 with the Eurotransplant (ET) and United Kingdom (UK) systems. We simulated data for 500 waitlist kidney transplant candidates and 70 deceased donors. Each of the 70 donors was allocated to the best pair of listed candidates, taking into account the criteria of the three allocation systems under analysis. Subsequently, we compare the selected candidate’s groups to kidney transplant. The Portuguese organ allocation model selects candidates with a greater number of incompatibilities with the donor compared to the other two models. Under the Portuguese system’s rules, candidates have a greater age difference with the respective donors (median = 12.5 years) than those selected by the ET system (10 years) or the UK system (8 years). The Portuguese model selected more hypersensitized candidates (15%), but this difference was not statistically significant when compared to the percentage of hypersensitized patients selected by the ET model (10.7%). The Portuguese model has less equity than the other two models under analysis, since the observed disadvantages regarding the number of incompatibilities and age differences with the respective donor are not compensated for by the selection of patients with longer time on dialysis.info:eu-repo/semantics/publishedVersio

Measuring kidney transplantation activity

[ENG] Kidney allocation from cadaveric donors must balance two main principles: medical utility and justice. The principle of medical benefit is gauged by maximizing efficiency in the use of organs and the principle of justice by its effectiveness, ensuring that all patients have a reasonable opportunity of transplantation. In this paper we present some metrics that, when applied to candidates for kidney transplantation, will help in the best judgment defining kidney allocation systems. Knowing the prevalence and incidence (per year, per million inhabitants) of kidney transplant, candidates demographic factors, such as: sex, age groups, and socioeconomic status; as well as clinical and immunological characteristics: blood group, Panel Reactive Antibody values, Body Mass Index, type of dialysis, cause of renal failure, and comorbidities; allows for an objective comparison of allocation programmes. The waiting time for transplantation should be measured as the median time between the start of dialysis and transplantation of wait -listed patients each year. By using the Cox regression analysis, with time on dialysis for transplantation as a dependent variable and clinical, socio -demographic factors as independent variables, we will shed light on which characteristics affect the access to transplantation.[PT] A distribuição de rins de dador cadáver deve equilibrar dois princípios fundamentais: a utilidade médica e a justiça. O principio do beneficio médico e aferido através da maximização da eficiência no uso dos órgãos, enquanto que o principio da justiça visa garantir que todos os candidatos tenham uma oportunidade razoável de transplante. Neste artigo, apresentamos algumas métricas que, quando aplicadas a candidates a transplante de rim, ajudarão na melhor avaliação e definição de sistemas de distribuição de rins. Conhecer a prevalência e incidência (por ano e por milhão de habitantes) dos transplantes de rim, fatores demográficos dos candidatos, tais como: sexo, faixa etária e nível socioeconómico; bem como as suas características clinicas e imunológicas: grupo sanguíneo, os valores do painel reativo de anticorpos, índice de massa corporal, tipo de dialise, a causa da insuficiência renal e co -morbilidades; permite uma comparação objetiva de programas distribuição. O tempo de espera para o transplante deve ser medido como a mediana do tempo entre o início da dialise e o transplante dos doentes em lista de espera em cada ano. Através da analise de regressão de Cox, com o tempo em dialise para transplante como variável dependente e os fatores clínicos e sócio-demográficos como variáveis independentes, e possível identificar as características que afetam o acesso ao transplante

Measuring access to Kidney transplantation

ORAL SESSIONS - Best AbstractsKidney allocation from cadaveric donors must balance two main principles: medical utility and justice. The principle of medical benefit is gauged by maximizing efficiency in the use of organs, and the principle of justice by its effectiveness ensuring that all patients have a reasonable opportunity to be transplanted. The survival benefit of transplant patients when compared with dialyzed values is well described even after adjusting for age, comorbidities, albumin and Body Mass Index (BMI). This benefit is also observed in patients over the age of 60 years. Several factors are related to transplant efficiency: maximization of HLA matching for patients that are more relevant (children and youth), preference for children; minimization of ischemia time, and the relation of life expectancy of the graft with life expectancy of the receptor. The factors related to justice are: reduction of waiting times, and greater equity of access for patients regardless of their race, blood group, HLA homozygosity and geographic location. There are socio-demographic and immunological factors associated with longer waiting time for kidney transplantation, such as: age, blood group or sensitization against HLA antibodies.Knowing the prevalence and incidence (per year, per million inhabitants) of kidney transplant candidates’ demographic factors such as: sex, age groups, socioeconomic status, clinical and immunological characteristics: blood group, PRA values, BMI, type of dialysis, cause of renal failure, and comorbidities; allows for an objective comparison of allocation programs. The waiting time for transplantation should be measured as the median time between the start of dialysis and transplantation of wait listed patients each year. By using the Cox regression analysis, with time on dialysis to transplantation as a dependent variable and clinical and socio-demographic factors as independent variables, will shed light on which characteristics most affect the access to transplantation. Only by defining and applying standardized metrics to kidney transplant candidates over time, is it possible to make informed decisions when debating organ allocation rules. “What gets measured gets improved”

Applying virtual crossmatch approach in portuguese kidney transplants

ORAL SESSIONS - Best AbstractsPresence of donor specific antibodies anti-human leukocyte antigen (HLA) is generally a contra-indication for transplantation and nowadays the identification of these antibodies are part of most pre-transplantation evaluations. In Portugal, the implemented protocol for the registration and maintenance of the active list for kidney transplant includes a complement-dependent cytotoxity (CDC) panel-reactive antibody (PRA) screening method, and Luminex technology for detecting and characterizing HLA alloantibodies. Under the current Portuguese kidney allocation system from deceased donors, implemented in August 2007, deceased donor kidneys are primarily allocated via ABO identical and time on dialysis with extra points to hyperimmunized patients, namely PRA CDC>50%. Additional risk for the candidate or transplant organ can be represented by a proposed calculated PRA (cPRA) based upon unacceptable HLA antigens detected by Luminex to which the patient has been sensitized. These unacceptable HLA antigens used to generate cPRA represents a ‘virtual’ crossmatch (XM). Sensitized patients are less likely to be matched with a suitable donor organ. Even after clearing the hurdle of procuring a living donor, it is still possible that this is not sufficient due to the likelihood of having a XM-positive. In these cases and in the presence of incompatible blood type between recipients and their intended living donors, kidney paired donation (KPD) can provide an answer by facilitating exchanges between willing donors’ kidneys. A national Portuguese KPD program, when realized, may prevent the current loss of a significant number of suitable living donors and reduce waiting list time for a deceased donor. An upgrade of a suggested point system in a Portuguese KPD program will be the use of cPRA instead of the values of PRA CDC. In Portugal, the virtual XM approach simply represents the optimization of an existing technique

Candidatos hipersensibilizados a transplantação renal em Portugal

[ENG] The presence of donor specific anti-HLA antibodies is generally a contraindication for transplantation and nowadays the identification of these antibodies are part of most pre-transplantation evaluations. In Portugal, the implemented protocol for registration and maintenance of the active list for kidney transplant includes a complement -dependent cytotoxity (CDC) panel-reactive antibody (PRA) screening method, and Luminex technology for detecting and characterizing HLA alloantibodies. Under the current Portuguese kidney allocation system from deceased donors, implemented in August 2007, deceased donor kidneys are primarily allocated via ABO identical and time on dialysis with extra points to hyperimmunized patients, namely PRA CDC > 50%. Additional risk for the candidate or transplant organ can be represented by a proposed calculated PRA (cPRA) based upon unacceptable HLA antigens detected by Luminex to which the patient has been sensitized. These unacceptable HLA antigens used to generate cPRA represents a virtual crossmatch (XM). Sensitized patients are less likely to be matched with a suitable donor organ. Even after clearing the hurdle of procuring a living donor, it is still possible that this is not sufficient due to the likelihood of having an XM-positive. In such cases, and in the presence of incompatible blood type between recipients and their intended living donors, kidney paired donation (KPD) can provide an answer to this catch by facilitating exchanges between willing donors kidneys. A national Portuguese KPD programme, when realized, may prevent the current loss of a significant number of suitable living donors and reduce waiting list time for a deceased donor. An upgrade of a suggested point system in a Portuguese KPD programme will be the use of cPRA instead of the values of PRA CDC. In Portugal, the virtual XM approach just represents the optimization of an existent technique.[PT] A presença de anticorpos anti-HLA específicos do dador é geralmente uma contraindicação para transplante e, hoje em dia, a identificação destes anticorpos é parte de muitos protocolos de avaliação pré--transplante. Em Portugal, o protocolo implementado para o registo e manutenção em lista activa para transplante de rim, inclui um método de pesquisa em painel reactivo de anticorpos (PRA) por citotoxicidade dependente do complemento (CDC) e a tecnologia Luminex para detectar e caracterizar aloanticorpos HLA. Segundo as actuais normas para a selecção do par dador-receptor em homotransplantação com rim de cadáver, implementadas em Agosto de 2007, a distribuição destes órgãos é prioritariamente isogrupal, contabilizando o tempo em diálise com pontos extra paras doentes imunizados, nomeadamente PRA CDC>50%. Um risco adicional para os candidatos a transplante de órgãos pode ser representado pelo proposto PRA calculado (cPRA), que tem por base antigénios HLA não aceitáveis, detectados por Luminex e para os quais os doentes estão sensibilizados. Estes antigénios HLA não aceitáveis usados para gerar o cPRA representam um crossmatch (XM) virtual. Os doentes sensibilizados têm uma menor probabilidade de encontrar um dador de órgãos admissível e mesmo depois de ultrapassada a barreira de encontrar um dador vivodisponível, é possível que isto não seja suficiente devido ao risco elevado de ter um XM positivo. Nestes casos e quando há incompatibilidade ABO entre um receptor e o seu potencial dador vivo, a troca de dadores vivos de rim (TDR) pode ser a resposta a este problema facilitando a consumação de transplantes compatíveis. Um programa nacional de TDR, quando implementado, pode evitar o actual desperdício de possíveis dadores vivos de rim e potencialmente reduzir o tempo de espera em lista para transplante com dador cadáver. Uma melhoria a um sugerido sistema de pontuação num programa Português de TDR será a utilização do cPRA em substituição dos valores de PRA CDC. Em Portugal, a abordagem de XM-virtual apenas representa a optimização de técnicas já existentes