Les modifications post-traductionnelles non enzymatiques des protéines, comme la glycation, l'oxydation ou la carbamylation, participent au vieillissement des tissus. Certaines maladies chroniques constituent des contextes pathologiques favorisant ces modifications chimiques. La carbamylation est une réaction encore peu étudiée à ce jour, qui correspond à la fixation de l'acide isocyanique, principalement dérivé de l'urée, sur les groupements aminés des protéines. Cette réaction mène à la formation de produits de carbamylation (CDP), parmi lesquels l'homocitrulline. Des études in vitro ont montré que la carbamylation participait à l'altération des propriétés structurales et fonctionnelles des protéines tissulaires et plasmatiques. Néanmoins, le devenir tissulaire des CDP reste encore non élucidé. Notre travail a consisté à évaluer la carbamylation des protéines tissulaires dans un contexte in vivo au cours de l'insuffisance rénale chronique (IRC) et du vieillissement. Ces études ont montré que la carbamylation était une réaction physiologique observée au cours du vieillissement et amplifiée au cours de l'IRC, menant à l'accumulation des CDP dans les tissus. Cette modification a particulièrement lieu au niveau du collagène de type I mais aussi au niveau de l'élastine, deux protéines matricielles à longue demi-vie. Ces résultats peuvent être mis en lien avec les troubles infectieux et inflammatoires observés au cours du vieillissement et de l'IRC. Par ailleurs, l'organisme semble capable de limiter ce processus de carbamylation, ce qui permet d'envisager des investigations supplémentaires dans l'optique de développer des stratégies préventives ou thérapeutiques. / Non-enzymatic post-translational modifications of proteins, such as glycation, oxidation, and carbamylation, are associated with tissue aging. Chronic diseases are pathological contexts known for amplifying these chemical modifications. A still poorly investigated reaction is carbamylation, or the binding of isocyanic acid, a byproduct principally derived from urea, to protein amino groups. This process leads to the formation of carbamylation-derived products (CDPs) such as homocitrulline. In vitro experiments have shown that carbamylation contributes to the alteration of structural and functional properties of various tissue and plasma proteins. The metabolic fate of carbamylated proteins in vivo, however, is still unclear.Herein, we have evaluated tissue carbamylation rate during chronic renal failure (CRF) and aging in vivo. Our results show that carbamylation occurs physiologically during aging and is amplified during CRF, leading to an accumulation of CDPs in tissues. This reaction affects more intensely type I collagen but also affects elastin, both extracellular compounds with long half-lives. These results could be linked with infectious and inflammatory disorders observed in aging and CRF. Moreover, the organism seems to be able to limit the carbamylation process, suggesting that further studies could develop preventive or therapeutic strategies.

People living with renal failure experience enormous challenges, yet very little is known about life with this disease. The goal of this research was to gain an integrated understanding of the lives of people with renal failure. An understanding of life with renal failure that includes cultural, institutional and historical contexts may provide health care practitioners with the kind of information and insights necessary to improve medical practice. Thus far, medical practice has been based on a biomedical model of care that focuses almost exclusively on the physical aspects of illness. From this perspective, people with kidney disease are seen as autonomous and rational individuals. In this research, a sociocultural multiple case study approach was utilized in order to gain a situated understanding of life for four people with renal disease. This research revealed that life with renal failure is work. While it is the people living with renal failure who do the bulk of the work, friends and family also work to "live" with renal disease. Participants and their significant others learn about and become experts on life with this disease. A gap was found between practitioners' understanding of disease and participants' lived experience — resulting in many negative repercussions. Medical-based knowledge is lacking because it does not consider the three relevant sources of knowledge: practitioners, participants and participants' significant others. This research argues for a bridge between the home world and the hospital world, so that a broader community of practice is created. An account of the lived experience of people with renal failure that includes these factors can inform "best practice" because it provides a richer and more authentic picture of life with this illness. It is from this perspective that health care practitioners can begin to broaden their understanding of renal failure as it is "lived", and, so informed, can better provide the kinds of education and support that will enhance the lives of people with this illness. / Education, Faculty of / Educational and Counselling Psychology, and Special Education (ECPS), Department of / Graduate

We accessed data on patients undergone peritoneal dialysis (PD), a technique that is underused in most countries and is not usually employed as the initial therapeutic option. The study aimed to characterize the DP program at a reference unit in the Northeast Region of Brazil. It was based on a retrospective cohort study that evaluated the clinical and socio-demographic profile, treatment history and causes of death of 565 incident patients who remained in PD for at least 30 days. Results were obtained: mean age was 54 ± 19 years when they started on PD. Males were 55%, 38% from Aracaju, 62% from Sergipe, 76% had <4 years of schooling and 88% earned <5 minimum wages as family income. Diabetic nephropathy was the main etiology (25%) and 77% were hypertensive. There was 9% of late referencing. The majority started on PD as the first dialytic procedure (53%), and (58%) as an emergency. The patients remained in PD for an average of 710.5 (± 714.2) days. PD was the initial dialysis modality for 302 patients (53%). A total of 676 peritoneal catheters were implanted, mean of 1.19 / patient. The median survival of the PD technique was 83.1 months, with a rate of 85.1% in 2 years and 61.1% in 5 years. The median survival of patients was 32.9 months for patients without DM, with a 2-year survival rate of 52.4% and a 5-year survival rate of 22.3. During the study, 353 individuals (62%) died. The etiology of renal disease was identified in 37% of the cases. The odds ratio (OR) of death of those who were referred late was 2,032 times greater than those who did conservative treatment. In conclusion, despite non favorable social indices, survival, peritonitis and complications rates were similar to those described in the literature. / Este estudo aborda a diálise peritoneal (DP), técnica que se mostra subutilizada na maioria dos países e geralmente não é oferecida como opção terapêutica inicial. Tem como objetivo caracterizar os resultados do programa de DP, avaliar frequência, etiologia e fatores associados à peritonite em pacientes sob DP em um centro de referência na região nordeste do Brasil. Avaliou a partir de um estudo de coorte retrospectivo, o perfil clínico e sociodemográfico, histórico de tratamento e causas de óbito associadas a fatores relacionados a peritonite de 565 pacientes incidentes que permaneceram em DP por pelo menos 30 dias. Foram resultados obtidos: a média de idade foi 54±19 anos quando iniciaram em DP. Sexo masculino foi 55%, sendo 38% procedentes de Aracaju, 62% residentes no interior de Sergipe, 76% com <4 anos de estudo e 88% com renda familiar <5 salários mínimos. Nefropatia diabética foi a principal etiologia (25%) e 77% eram hipertensos. Houve 9% de referenciamento tardio. A maioria iniciou em diálise por DP (53%), sendo 58% de forma emergencial. Os pacientes permaneceram em DP por, em média, 710,5 dias. Foram implantados 676 cateteres peritoneais, média de 1,19/paciente. A maioria dos pacientes (59%) não apresentou peritonite. O índice global de peritonite foi de 0,32 episódio/paciente.ano. O Staphylococus aureus foi o germe mais prevalente (23%). Houve cura da peritonite em 71% dos casos. Identificou-se maior risco de peritonite nos pacientes com histórico de infecção do sítio de saída do cateter peritoneal. A sobrevida mediana da técnica de DP foi de 83,1 meses, com taxa de 85,1% em 2 anos e de 61,1% em 5 anos. A sobrevida mediana dos pacientes foi de 32,9 meses para os pacientes sem DM, com taxa de sobrevida em 2 anos de 52,4% e em 5 anos de 22,3%. Foram a óbito 353 indivíduos (62%). A etiologia da doença renal foi identificada em 37% dos casos. A chance de risco (OR) de óbito de quem tem referenciamento tardio é 2,032 vezes maior do que quem fez tratamento conservador. Como conclusão obteve-se que a despeito dos indicadores sociais ruins da população estudada, sobrevida, taxas de peritonite e complicações se assemelharam ao descrito na literatura. / Aracaju, SE

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Orientador: Luis Cuadrado Martin / Coorientador: Fernando Antonio de Almeida / Resumo: Introdução: as doenças cardiovasculares representam a maior causa de mortalidade nos pacientes renais crônicos antes e após o transplante renal, dentre elas a doença coronariana apresenta destaque especial. Preditores de risco tem sido usados no seu diagnóstico que é desafiador. Poucos trabalhos validaram preditores clínicos de seleção para exames invasivos para o diagnóstico de doença arterial coronariana (DAC) antes do transplante renal.Objetivo: avaliar a frequência e poder discriminatório de preditores clínicos da presença da doença arterial coronariana em pacientes renais crônicos em programa de diálise candidatos ao transplante renal, avaliar a performance da fórmula de Gowdak e colaboradores de risco de doença arterial coronariana e verificar a associação entre doença arterial coronariana e desfechos no grupo estudado.Métodos: foram analisadas as cinecoronariografias de candidatos ao transplante renal de dois centros de transplante renal do estado de São Paulo, realizadas entre março de 2008 e abril de 2013. Foi realizado estudo transversal para verificar o poder preditivo de parâmetros clínicos para a presença de doença coronária significativa (estenose ≥70% em uma ou mais artérias epicárdicas ou ≥ 50% no tronco da coronária esquerda). Adicionalmente, verificou-se o poder discriminatório de um escore clínico de risco previamente estabelecido (que leva em conta presença de diabetes melito (DM), idade e manifestações clínicas de doença cardiovascular). Foi realizado... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Cardiovascular diseases are major causes of mortality in chronic renal failure patients before and after renal transplantation. Among them, coronary disease presents a special emphasis. Predictors of risk for coronary artery disease has been used for its diagnosis. Few studies have validated clinical predictors to selection patients for invasive procedures for the diagnosis of coronary artery disease (CAD) before renal transplantation. Objective: this study evaluated the frequency and discriminatory power of clinical predictors of coronary artery disease in chronic renal failure patients undergoing dialysis who were renal transplant candidates, assessed a previously developed scoring system (Gowdak et al.) for coronary artery disease, and we also checked the association between coronary artery disease and outcomes of the study group. Methods: coronary angiographies conducted between March 2008 and April 2013 from candidates for renal transplantation from two transplant centers in São Paulo state were analyzed. Cross-sectional study was conducted to verify the predictive power of clinical parameters for the presence of significant coronary artery disease (≥70% stenosis in one or more epicardial artery or ≥ 50% in the left main coronary artery). In addition, the discriminating power of a previously established clinical risk score was assessed (which takes account of diabetes mellitus (DM), age and clinical manifestations of cardiovascular disease). It was also conducted observational longitudinal study and drew up survival curves according to the angiographic diagnosis to verify the association between the presence of coronary heart disease and outcomes. Results: we screened 128 patients, of which 23 were excluded. The prevalence of coronary atheromatosis of any grade was 60/105 (57%) and significant coronary atheromatosis was 30/105 (29%) in the... (Complete abstract click electronic access below) / Doutor

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1 electroninc resource (ix, 86 leaves) / This study aimed at exploring and describing the perceptions of relatives of patients with chronic renal failure regarding kidney donation. The number of patients suffering from chronic renal failure awaiting kidney transplantation is on the increase, while the treatment they get in the interim is not cost effective. The researcher used qualitative descriptive and exploratory research using the Potter and Perry’s Health Belief Model. She applied purposive sampling and used semi structured interviews to collect data from 45 participants who were all relatives of patients coming for haemodialysis at a selected hospital in KwaZulu-Natal. Data analysis identified participants’ perceptions regarding chronic renal failure and kidney donation. Findings of the study revealed that most relatives were fully aware of kidney donation, but fear and lack of knowledge regarding kidney transplantation were the main barriers to them offering themselves for kidney donation. The researcher recommends that the Renal Transplant Multidisciplinary Committee should ensure the public is informed about kidney donation and more intensive education should be given to the relatives of patients suffering from chronic renal failure at an early stage in the illness to give them more time to come to terms with the concept of kidney donation. / Health Studies / M.A. (Health Studies)

This study aimed at exploring and describing the perceptions of relatives of patients with chronic renal failure regarding kidney donation. The number of patients suffering from chronic renal failure awaiting kidney transplantation is on the increase, while the treatment they get in the interim is not cost effective. The researcher used qualitative descriptive and exploratory research using the Potter and Perry’s Health Belief Model. She applied purposive sampling and used semi structured interviews to collect data from 45 participants who were all relatives of patients coming for haemodialysis at a selected hospital in KwaZulu-Natal. Data analysis identified participants’ perceptions regarding chronic renal failure and kidney donation. Findings of the study revealed that most relatives were fully aware of kidney donation, but fear and lack of knowledge regarding kidney transplantation were the main barriers to them offering themselves for kidney donation. The researcher recommends that the Renal Transplant Multidisciplinary Committee should ensure the public is informed about kidney donation and more intensive education should be given to the relatives of patients suffering from chronic renal failure at an early stage in the illness to give them more time to come to terms with the concept of kidney donation. / Health Studies / M.A. (Health Studies)

O excesso de adenina na dieta (ADE) promove precipitação intratubular de cristais, levando à instalação de uma nefrite intersticial progressiva e perda da função renal. Observações recentes indicam que a sobrecarga de ADE em camundongos em que os genes para TLR-2, -4, MyD88, ASC ou caspase-1 foram inativados provoca menos dano renal do que quando administrado a camundongos selvagens, sugerindo a existência de um papel patogênico para a ativação de TLRs e a montagem de inflamassomas nesse modelo. O presente estudo foi concebido para investigar se outro importante componente da imunidade inata, o sistema NF-B, também exerce papel patogênico na nefropatia associada ao excesso de ADE. Ratos Munich-Wistar machos e adultos foram divididos em 3 grupos: C (N=17), ração padrão; ADE (N=17), ADE na ração, 0,7% durante 1 semana e 0,5% durante 2 semanas; ADE+PDTC (N=14), ADE administrada como descrito anteriormente, associada ao inibidor do NF-B, pirrolidina ditiocarbamato (PDTC), 120 mg/kg/dia na água do bebedouro. Após 3 semanas, observou-se deposição de numerosos cristais no tecido renal, em sua maioria no interior de granulomas de corpo estranho, acompanhada de intensa atividade proliferativa tubulointersticial. Uma parte dos cristais apareceu envolvida por uma camada de células aparentemente derivadas do epitélio tubular, que pareciam segregar os precipitados e, em alguns casos, expulsá-los ao interstício. Essas alterações associaram-se a uma grande expansão da área intersticial, com deposição de colágeno, além de hipotrofia glomerular. Foi possível ainda demonstrar um aumento da expressão da interleucina-6, do interferon-, da proteína específica de fibroblastos (FSP-1) e da proteína quimiotática para macrófagos (MCP-1). A abundância do IKK-, uma quinase ativadora do sistema NK-B, mostrou-se também acentuadamente elevada nesses ratos. O tratamento com PDTC normalizou a expressão do IKK-, diminuindo o número de granulomas e a proliferação celular, além de atenuar fortemente a fibrose e o declínio da função renal. Esses achados, que contribuem para elucidar os mecanismos de formação de granulomas no modelo de sobrecarga de adenina, são consistentes com o conceito de que o sistema NF-B é ativado pela precipitação intratubular de cristais e contribui, juntamente com outros mecanismos ligados à imunidade inata, para iniciar a intensa resposta inflamatória associada a esse modelo. Descritores: 1.Insuficiência renal crônica 2.Adenina 3.Imunidade inata 4.NF-kappa B 5.GranulomaO excesso de adenina na dieta (ADE) promove precipitação intratubular de cristais, levando à instalação de uma nefrite intersticial progressiva e perda da função renal. Observações recentes indicam que a sobrecarga de ADE em camundongos em que os genes para TLR-2, -4, MyD88, ASC ou caspase-1 foram inativados provoca menos dano renal do que quando administrado a camundongos selvagens, sugerindo a existência de um papel patogênico para a ativação de TLRs e a montagem de inflamassomas nesse modelo. O presente estudo foi concebido para investigar se outro importante componente da imunidade inata, o sistema NF-B, também exerce papel patogênico na nefropatia associada ao excesso de ADE. Ratos Munich-Wistar machos e adultos foram divididos em 3 grupos: C (N=17), ração padrão; ADE (N=17), ADE na ração, 0,7% durante 1 semana e 0,5% durante 2 semanas; ADE+PDTC (N=14), ADE administrada como descrito anteriormente, associada ao inibidor do NF-B, pirrolidina ditiocarbamato (PDTC), 120 mg/kg/dia na água do bebedouro. Após 3 semanas, observou-se deposição de numerosos cristais no tecido renal, em sua maioria no interior de granulomas de corpo estranho, acompanhada de intensa atividade proliferativa tubulointersticial. Uma parte dos cristais apareceu envolvida por uma camada de células aparentemente derivadas do epitélio tubular, que pareciam segregar os precipitados e, em alguns casos, expulsá-los ao interstício. Essas alterações associaram-se a uma grande expansão da área intersticial, com deposição de colágeno, além de hipotrofia glomerular. Foi possível ainda demonstrar um aumento da expressão da interleucina-6, do interferon-, da proteína específica de fibroblastos (FSP-1) e da proteína quimiotática para macrófagos (MCP-1). A abundância do IKK-, uma quinase ativadora do sistema NK-B, mostrou-se também acentuadamente elevada nesses ratos. O tratamento com PDTC normalizou a expressão do IKK-, diminuindo o número de granulomas e a proliferação celular, além de atenuar fortemente a fibrose e o declínio da função renal. Esses achados, que contribuem para elucidar os mecanismos de formação de granulomas no modelo de sobrecarga de adenina, são consistentes com o conceito de que o sistema NF-B é ativado pela precipitação intratubular de cristais e contribui, juntamente com outros mecanismos ligados à imunidade inata, para iniciar a intensa resposta inflamatória associada a esse modelo / Excessive dietary adenine (ADE) promotes intratubular precipitation of crystals, leading to the installation of progressive interstitial nephritis and renal function loss. Recent observations indicate that ADE overload in mice in which genes for TLR-2, -4, MyD88, ASC or caspase-1 were inactivated causes less renal damage than when administered to wild-type mice, suggesting the existence of a pathogenic role for the activation of TLRs and the assembly of inflamassomes in this model. The present study was designed to investigate whether another important component of innate immunity, the NF-B system, also plays a role in the pathogenesis of the nephropathy associated with excess ADE. Adult Male Munich-Wistar rats were distributed among three groups: C (n = 17), receiving standard diet; ADE (N = 17), given ADE in the diet at 0.7% for 1 week and 0.5% for 2 weeks; and ADE + PDTC (N = 14), receiving ADE as described above, associated with the NF-B inhibitor, pyrrolidine dithiocarbamate (PDTC), 120 mg/kg/ day in drinking water. After three weeks, there was widespread deposition of crystals in the renal tissue, mostly within granulomas, accompanied by florid tubulointerstitial proliferative activity. Part of these crystals was enclosed in a layer of cells apparently derived from the tubular epithelium, which appeared to segregate the precipitates, and in some cases, to extrude them to the interstitium. These changes were associated with marked interstitial expansion, collagen deposition, and glomerular hypotrophy. Increased expression of interleukin-6, interferon-, fibroblast specific protein (FSP-1) and macrophage chemoattractant protein (MCP-1) were also shown. The abundance of IKK-, a kinase that activates the NF-B system, was also markedly elevated in these mice. Treatment with PDTC normalized the expression of IKK-, reducing the number of granulomas and cell proliferation, and strongly attenuated interstitial fibrosis and the decline of renal function. These findings, which contribute to illuminate some mechanisms of granuloma formation in the ADE overload model, are consistent with the concept that the NF-B system is activated by intratubular precipitation of crystals and contributes, along with other mechanisms related to innate immunity, to initiate the intense inflammatory response associated with this model

A Insuficiência Renal Crônica Terminal (IRCT) é uma doença crônica nãotransmissível e um problema de saúde pública, constituindo uma das principais causas de morte e incapacitação no mundo. A condição crônica de saúde é uma situação estressante e fonte de novos estressores que são enfrentados, de acordo com o significado que têm para os envolvidos. Os modos de enfrentamento podem amenizar os efeitos do estresse, favorecendo o processo adaptativo. Objetivos: Analisar os modos de enfrentamento das pessoas com IRCT frente à situação de doença e ao tratamento por hemodiálise, segundo variáveis sociodemográficas, clínicas e hábitos de vida. Material e método: Trata-se de um estudo descritivo, transversal e populacional, que utiliza análise quantitativa, desenvolvido no Instituto de Urologia e Nefrologia de São José do Rio Preto (IUN), onde foram entrevistados 107 pacientes acometidos por IRCT em tratamento hemodialítico há seis meses ou mais, adultos (pacientes com 18 anos ou mais), orientados, tendo condições de responder aos questionários propostos sem prejuízo nas respostas; que concordaram em participar do estudo, assinando o termo de consentimento livre e esclarecido. Os instrumentos utilizados foram o Inventário de Estratégias de Enfrentamento de Folkman e Lazarus (1985) e um roteiro de entrevista semi-estruturada para caracterização da população elaborado para este estudo. Resultados: A maioria das pessoas entrevistadas era do sexo masculino, de idade adulta (idade entre 18 e 59 anos), branca, tinha companheiro (a), morava com a família, tinha escolaridade entre zero e oito anos de estudo, era aposentada, não trabalhava, tinha atividade de lazer, não praticava atividades físicas e tinha religião. As principais causas da IRCT foram GNC, diabetes mellitus, causa indeterminada e hipertensão arterial. Os modos de enfrentamento que obtiveram maiores escores médios foram relacionados aos fatores reavaliação positiva, resolução de problemas e fuga-esquiva, evidenciando o uso mais freqüente dos modos de enfrentamento focados no problema. As mulheres apresentaram escores médios mais elevados para todos os fatores; idosos tiveram escores médios mais elevados nos fatores confronto, afastamento e fuga-esquiva; pessoas com 12 ou mais anos de estudo apresentaram escores médios mais elevados que pessoas com menos anos de estudo para os fatores autocontrole, suporte social, fuga-esquiva, resolução de problemas e reavaliação positiva; pessoas que referiram trabalhar apresentaram escores médios mais elevados para os fatores autocontrole, suporte social, resolução de problemas e reavaliação positiva; pessoas que realizaram transplante obtiveram escores mais elevados nos fatores autocontrole, suporte social, aceitação de responsabilidades, fuga-esquiva, resolução de problemas e reavaliação positiva; pessoas que não tinham religião obtiveram os menores escores médios para todos os fatores. Conclusão: a identificação dos modos de enfrentamento das pessoas, em tratamento hemodialítico, pode facilitar o planejamento da assistência, favorecendo a adaptação das pessoas aos estressores associados à IRCT e ao tratamento hemodialítico. / Terminal Chronic Renal Failure (TCRF) is a non-transmissible chronic disease and one problem of public health, constituting one of the main causes of death and disabilities in the world. The chronic condition of health is a stressful situation and source of new stressors, that are cope in accordance with the meaning that has for the involved ones. The ways of coping can brighten up the effect of the stress it favoring the adaptation. Aims: To analyze the ways of coping of the people with TCRF front the situation of disease and the hemodialysis treatment, according to social, demography, clinical variables and habits of life. Material and method: One is about a descriptive, transversal and population study, that uses quantitative analysis, developed in the Institute of Urology and Nephrology of São Jose do Rio Preto (IUN), where 107 patients with TCRF in hemodialysis treatment had been interviewed, they have six months or more , adults (patient with 18 years or more), guided, having conditions to answer to the questionnaires considered without damage in the answers; that they had agreed to participating of the study signing the term of free and clarified assent. The instruments had been used was Ways of coping of Folkman and Lazarus (1985) and a half-structuralized script of interview for characterization of the people, made for this study. Results: The majority of the interviewed people was mans, adults (age between 18 and 59 years), white, had study between 0 and 8 years and it had religion. The main causes of the TCRF had been GNC, diabetes mellitus, indetermined cause and arterial hipertension. The ways of coping that had the hight medium scores had been related to the factors positive reappraisal, planful problem-solving and escape-avoidance, evidencing the most frequent use in the problem-focuse coping. The women had higher médium score for all the factors; old had had higher medium scores in the factors confrontive coping, distancing and escapeavoidance; people that not work higher médium scores for the factors self-control, seeking social support, planful problem-solving and positive reppraisal; people who had carried through transplant, had gotten higher médium scores in the factors self-control, seeking social support, accepting responsibility, escape-avoidance, planful problem-solving and positive reppraisal; people who did not have religion had gotten the minors medium scores for all the factors. Conclusion: the identification in the ways of coping of the people in hemodialysis treatment, can facilitate to the planning of the assistance, favoring the adaptation of the people to the stressors associates to the TCRF and the hemodialysis treatment.