Pacientes submetidos por longos períodos à diálise peritoneal (DP) podem evoluir com fibrose e redução da capacidade de ultrafiltração da membrana peritoneal (MP). Essas alterações da MP são desencadeadas pela exposição prolongada às soluções de diálise peritoneal, peritonites de repetição e irritantes químicos que induzem inflamação, neoangiogênese e fibrose da MP. A ativação da via Transforming Growth Factor (TGF-beta)/Smad é um fundamental mecanismo mediador da fibrogênese peritoneal. Sendo assim, drogas que inibam a via TGF-beta/Smad são de especial interesse no tratamento da FP. O ácido valpróico (VPA) é um inibidor das histona desacetilases (iHDAC), enzimas que regulam a conformação da cromatina e a expressão gênica, com atividade anti-inflamatória e antifibrótica. O presente estudo tem como objetivo principal avaliar o efeito do VPA em um modelo experimental de fibrose peritoneal em ratos. Vinte e quatro ratos Wistar machos (peso inicial de 280 - 320g) foram dividos em 3 grupos experimentais: CONTROLE (n=8), animais normais que receberam injeções de salina intraperitoneal (IP); FP (n=8), animais que recereberam injeções IP de gluconato de clorexidina (GC) diariamente por 15 dias para indução de fibrose peritoneal; FP+VPA (n=8), animais com FP e tratados com VPA. O ácido valpróico (300mg/kg) foi administrado por gavage diariamente por 15 dias, simultaneamente à indução de fibrose peritoneal. Ao fim dos experimentos, amostras do tecido peritoneal foram coletadas para realização de histologia, imunho-histoquímica (IH), imunofluorescência (IF) e biologia molecular. A análise da MP dos animais do grupo FP revelou um espessamento significativo da camada submesotelial devido ao acúmulo de matriz extracelular e infiltrado inflamatório. O tratamento com VPA foi capaz de prevenir significativamente o espessamento da MP, mantendo a espessura do peritôneo do grupo FP+VPA similar a do grupo CONTROLE. Com relação à função peritoneal, a administração de VPA evitou a queda da ultrafiltração e aumento do transporte peritoneal de glicose induzidos pelo GC. Além disso, o VPA impediu o aumento da expressão de miofibroblastos e de fatores associados à fibrose (TGF-beta, FSP-1 e fibronectina) induzidos pelo GC. Interessantemente, o VPA reduziu de maneira significativa a expressão da Smad3, mediador intracelular crítico da sinalização TGF-beta/Smad, em relação ao grupo FP. Por outro lado, os animais tratados com VPA apresentaram um aumento da expressão peritoneal de fatores antifibróticos como a BMP-7 e Smad7, proteínas que contrarregulam as ações do TGF-beta. Além de atenuar a fibrose peritoneal, o VPA apresentou efeitos anti-inflamatório e antiangiogênico, demonstrado pela menor expressão de citocinas pró-inflamatórias, fatores quimiotáticos para macrófagos (MCP-1) e VEGF no grupo FP+VPA quando comparado ao grupo FP. Em resumo, o VPA foi capaz de bloquear o espessamento por fibrose da MP e preservar a sua função, além de proteger o peritônio contra a neoangiogênese e inflamação. Além disso, o VPA induziu um aumento da expressão de fatores antifibróticos na MP. Os resultados apresentados neste trabalho chamam a atenção para mecanismos envolvidos nas modificações da MP induzidas pela DP ainda pouco explorados e que podem constiuir potenciais alvos na prevenção do desenvolvimento da fibrose peritoneal associada à DP / Long term peritoneal dialysis (PF) can induce peritoneal fibrosis and loss of ultrafiltration capacity of peritoneal membrane (PM). These peritoneal changes are due to prolonged exposure to peritoneal dialysis solutions, chemical irritants and acute peritonitis episodes that induce inflammation, neoangiogenesis and PM fibrosis. The Transforming Growth Factor (TGF-?) is the main mediator involved in the development of peritoneal fibrosis. Thus, drugs that inhibit the TGF-?/Smad pathway or inflammation are of particular interest in the treatment of PF. Valproic acid (VPA) is an histone deacetylase (HDAC) inhibitor. HDACs are enzymes that regulate chromatin conformation and gene expression. Recent studies have described HDACi as promising drugs in the treatment of inflammatory and fibrotic diseases. The main aim of this study was to evaluate the effect of VPA in an experimental model of peritoneal fibrosis in rats. Twenty four Wistar rats (initial weight of 280-320g) were divided into three experimental groups: CONTROL (n = 8), normal animals that received only saline ip; FP (n = 8), peritoneal fibrosis was induced by daily Gluconate Clorhexedine (GC) intraperitoneal (IP) injections for 15 days; FP+VPA (n = 8), animals with peritoneal fibrosis and treated with VPA. Daily valproic acid (300mg/kg) doses were administered by gavage simultaneously with the induction of peritoneal fibrosis in the FP+VPA group. At the end of experiments, the animals were submitted to euthanasia and samples of peritoneal tissue were collected for histology, immunocytochemistry, immunofluorescence, and molecular biology. Also, a functional peritoneal test was performed. The FP group showed a significant thickening of PM due to the accumulation of extracellular matrix and inflammatory cellular infiltration. VPA treatment was able to significantly prevent PM thickening, maintaining the peritoneal thickness of the VPA group similar to that of the CONTROL group. The VPA administration also preserved peritoneal function in the FP+VPA group, avoiding the reduction of ultrafiltration and increasing of peritoneal glucose transport induced by GC. According to the histological changes mentioned above, the VPA hampered the upregulation of the pro-fibrotic genes (TGF-beta, FSP-1, and fibronectin) and increase in the myofibroblasts expression induced by GC injections. Interestingly, the peritoneal expression of phosphorylated Smad3 detected by immunohistochemistry and Smad3 mRNA was significantly higher in the FP group. However, this effect was attenuated by VPA treatment. On the other hand, VPA was able to induce an increase in the expression of the antifibrotic factors, such as BMP-7 and Smad7, in the peritoneal membrane. Besides its antifibrotic activity, VPA also showed anti-inflammatory and anti-angiogenic effects. Animals of the FP+VPA group showed a significant reduction of the PM expression of pro-inflmmatory cytokines, macrophage chemoattractants and, VEGF expression when compared with FP group. In conclusion, we have shown that VPA inhibits the progression of peritoneal fibrosis in a CG-induced peritoneal fibrosis model in rats. VPA inhibited different and important mechanisms involved in peritoneal membrane modifications induced by PD, as activation of TGF-beta/Smad pathway, inflammation, and angiogenesis. Notably, VPA induced the expression of antifibrotic factors. Our results are very interesting and shed lights on a new perspective for the treatment of peritoneal fibrosis. However, this is an exploratory study and future studies are needed before to translate this experimental finding into clinical application

INTRODUÇÃO: A necessidade de diálise e a mudança iminente no estilo e qualidade de vida são grandes responsabilidades depositadas nos pacientes com doença renal crônica (DRC) em processo de escolha do método dialítico. Alguns dos temas mais frequentemente implicados na escolha de um ou outro método dialítico são depressão, ansiedade e estresse. Nos pacientes renais crônicos pré-dialíticos ainda não foi evidenciado se a ansiedade está associada a desfechos clínicos, tais como início da diálise, hospitalizações ou morte. Tem-se sugerido que a depressão afeta os desfechos clínicos em pacientes com DRC pré-dialítica, podendo impactar no estado nutricional e na redução da observância da diálise prescrita. O estresse é um fator muito comum em indivíduos com uma doença de longa duração, incluindo aqueles com DRC. Altos níveis de estresse podem ter um impacto nos resultados psicológicos e clínicos, além de contribuir para os comportamentos de saúde, como as preferências pelo método dialítico. MÉTODOS: Este é um estudo observacional prospectivo no qual 67 pacientes foram abordados em dois momentos: durante primeira consulta no Ambulatório Multidisciplinar de Orientações do serviço de Nefrologia HC-FMUSP e, depois, no período entre 1 e 3 meses após o início da diálise. Foram utilizados os instrumentos Escala Hospitalar de Ansiedade e Depressão (HADS), Escala de Estresse Percebido (PSS) e Questionário de fatores pessoais que interferem na escolha do método dialítico, instrumento elaborado pelo autor. Características demográficas e clínicas também foram avaliadas. RESULTADOS: A média de idade foi de 59±15 anos, em sua maioria homens (53,7%), brancos (59,7%) e casados (57,8%). As principais comorbidades foram HAS (83,6%) e DM (42,6%). As principais causas de DRC foram nefroesclerose (26,9%) e nefropatia diabética (22,4%). A média de eGFR por CKD-EPI foi 16±7. As medianas de escores de ansiedade, depressão e estresse foram, respectivamente, de 6 (4/10), 9 (5/12) e 30 (21/35). A partir dos valores de corte estabelecidos, 34,3% dos indivíduos foram considerados \"com ansiedade\" e 52,2% \"com depressão\". A comparação de escores de ansiedade revela não haver diferença entre homens e mulheres (p= 0,136), havendo, porém, tendência de maiores escores de depressão entre mulheres (p= 0,074) e de estresse entre homens (p= 0,081). Não foram observadas diferenças nos escores de ansiedade (p= 0,556), depressão (p= 0,467) e estresse (p= 0,971) entre grupos DP e HD. Houve correlação positiva entre ansiedade e depressão (r2= 0,574, p < 0,0001), ansiedade e estresse (r2= 0,555, p < 0,0001) e depressão e estresse (r2= 0,521, p < 0,0001). Após início da terapia dialítica, foram observadas reduções significativas nos escores de ansiedade (p < 0,0001), depressão (p < 0,0001) e estresse (p < 0,0001). Os motivos relacionados à família são os que mais influenciaram na escolha do método (32,8%, p= 0,165). A incompatibilidade com a rotina pessoal/de trabalho foi o principal motivo para não escolha do outro método dialítico (26,9%). CONCLUSÕES: Embora o processo de tomada de decisões na escolha do método dialítico esteja associado a altos escores de ansiedade, depressão e estresse, tais sintomas são atenuados de forma significativa após o início da terapia dialítica. Escores de ansiedade, depressão e estresse não foram determinantes na escolha do método dialítico / BACKGROUND: The need for dialysis and the imminent change in style and quality of life are great responsibilities deposited in patients with chronic kidney disease (CKD) in the process of choosing the dialysis modality. Some of the issues most often involved in choosing one or another dialytic method are depression, anxiety, and stress. In pre-dialysis CKD patients, it has not yet been shown whether anxiety is associated with clinical outcomes such as initiation of dialysis, hospitalization, or death. It has been suggested that depression affects clinical outcomes in patients with predialytic CKD, which may impact nutritional status and reduce adherence to prescribed dialysis. Stress is a very common factor in individuals with a long-term illness, including those with CKD. High levels of stress can have an impact on psychological and clinical outcomes, as well as contribute to health behaviors such as dialysis preferences. METHODS: This is a prospective observational study in which 67 patients were approached in two moments: during the first visit at the Dialysis Education Program of the HC-FMUSP Nephrology Service and then in the period between 1 and 3 months after the initiation of the dialysis. We used the Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS) and Survey on personal factors that affects the choice of the dialysis method, an instrument developed by the author. Demographic and clinical characteristics were also evaluated. RESULTS: The mean age was 59 ± 15 years, mostly men (53.7%), caucasian (59.7%) and married (57.8%). The main comorbidities were hypertension (83.6%) and DM (42.6%). The main causes of CKD were nephrosclerosis (26.9%) and diabetic nephropathy (22.4%). The mean eGFR by CKD-EPI was 16 ± 7. Median anxiety, depression and stress scores were, respectively, 6 (4/10), 9 (5/12) and 30 (21/35). According to the established cutoff values, 34.3% of the individuals were considered \"with anxiety\" and 52.2% \"with depression\". The comparison of anxiety scores revealed no difference between men and women (p= 0.136), but there was a tendency for higher depression scores among women (p= 0.074) and stress among men (p= 0.081). There were no differences in anxiety scores (p= 0.556), depression (p= 0.467) and stress (p = 0.971) between DP and HD groups. There was a positive correlation between anxiety and depression (r2 = 0.574, p < 0.0001), anxiety and stress (r2 = 0.555, p < 0.0001) and depression and stress (r2 = 0.521, p < 0.0001). After initiation of dialysis therapy, significant reductions in anxiety scores (p < 0.0001), depression (p < 0.0001) and stress (p < 0.0001) were observed. The reasons related to the family were the ones that influenced the choice of the method (32.8%, p= 0.165). The incompatibility with the personal / work routine was the main reason for not choosing the other dialytic method (26.9%). CONCLUSION: Although the decision-making process in the dialysis modality choice is associated with high anxiety, depression and stress scores, such symptoms are significantly attenuated after the initiation of dialysis therapy. Anxiety, depression, and stress scores were not determinant in the choice of dialysis method

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-08-04T13:20:22Z No. of bitstreams: 1 nataliamariadasilvafernandessuassuna.pdf: 21230396 bytes, checksum: 11fc04717340958f54acd5fd7282c5b8 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-08-08T18:07:29Z (GMT) No. of bitstreams: 1 nataliamariadasilvafernandessuassuna.pdf: 21230396 bytes, checksum: 11fc04717340958f54acd5fd7282c5b8 (MD5) / Made available in DSpace on 2017-08-08T18:07:29Z (GMT). No. of bitstreams: 1 nataliamariadasilvafernandessuassuna.pdf: 21230396 bytes, checksum: 11fc04717340958f54acd5fd7282c5b8 (MD5) Previous issue date: 2009-03-20 / O presente estudo utilizou registros sistematizados de dados nacionais e locais sobre pacientes em terapia renal substitutiva (TRS) fundamentais para o conhecimento epidemiológico da realidade do tratamento dialítico. Estes dados podem permitir uso mais racional dos recursos econômicos, identificação das intervenções, visando à melhoria da terapêutica, diminuição da morbimortalidade desses pacientes. No Brasil, a Sociedade Brasileira de Nefrologia, mantém, desde 1999, registros parciais sobre pacientes em TRS. Os objetivos do estudo foram coletar dados demográficos, clínicos, laboratoriais e desfechos (óbito, recuperação da função renal, transferência para hemodiálise, falência da técnica, transplante renal, tranferência para outro centro ou perda de seguimento) de pacientes em diálise peritoneal (DP) tratados em centros de todas as regiões do Brasil para descrição das características epidemiológicas desta população e avaliação dos fatores relacionados à falência da técnica e mortalidade. Para tal foi desenhado um estudo multicêntrico, envolvendo centros de todas as regiões do país, iniciado em dezembro de 2004 e com seguimento até outubro de 2007. Foi desenhado um software com os dados preenchidos off fine e enviados on fine a um servidor. Neste ponto, os dados foram extrídos em MySQL, sendo montada uma base de dados, posteriormente, transportada para o software estatístico SPSS 13.0 e SAS. Ao final, foram analisados 6.198 pacientes de 102 centros. Os resultados mostram que o Brasil apresenta um baixo número de pacientes em diálise peritoneal, com um viés de seleção para esta modalidade, onde a maioria dos pacientes apresenta inúmeras comorbidades tendo como indicação clínica "única possibilidade terapêutica ou indicação médica". Apesar disto, há um baixo índice de complicações infecciosas (1 episódio de peritonite/30 meses) e a taxa de saída no período inicial de 34 meses foi de 37,7%, com um média anual de 13,3%. A meta mais difícil de ser alcançada é a hemoglobina, notadamente em diabéticos e pacientes egressos de outras TRSs. A principal causa de saída foi óbito (21%), sendo as causas cardiovasculares as mais prevalentes (40%). Entre os principais fatores relacionados à mortalidade e falência da técnica foram encontrados a idade, diabetes mellitus, doença cardiovascular. Houve relação direta da mortalidade da população geral com a mortalidade da população em diálise peritoneal. Foram observadas diferenças regionais importantes quanto às taxas e motivos de saídas nas diversas regiões do país, bem como, a ocorrência da "epidemiologia reversa" da obesidade nesses pacientes. O estudo permitiu traçar o perfil epidemiológico dos pacientes em diálise peritoneal no Brasil e concluir que, a despeito do importante viés de seleção, nosso país apresenta uma diálise peritoneal adequada, comparada a países desenvolvidos europeus. / Systematic registers of local and national data on patients in renal replacement therapy (TRS) are critical to the epidemiological knowledge of the reality of the dialysis treatment. These data may allow more rational use of economic resources, identify interventions to improve the treatment, and to decrease morbidity and mortality of these patients. In Brazil, the most recent dialysis register made available by the Brazilian Society of Nephrology is based on data obtained from 1999 patients on renal replacement therapy. This study aimed to collect demographic, clinical, laboratory and outcomes (death, recovery of renal function, transfer to hemodialysis, the technical failure, kidney transplantation, transfer to another center or loss of follow-up) of patients on peritoneal dialysis (PD) treated in dialysis clinics located in all regions of Brazil to describe the epidemiological characteristics of this population and assess the factors related to the risk of the technique failure and mortality of patients. A multicenter study was designed involving patients of 102 centers in all the regions of the Brazil, initiated in December of 2004, with the last set of date obtained in October 2007. A software was designed with the data registered offline and sent online to a central server. The data were extracted in MySQL and originating a database that was initially validated and then transfered to the statistical software SPSS 13.0 and SAS. This extraction was performed in two stages. At the end of the study, 6198 patients were analyzed. Brazil has a low number of patients on peritoneal dialysis, with a selection bias for this treatment modality, where the majority of patients presents numerous co-morbidities and and has peritoneal dialysis as the only therapeutic option. There is a low rate of infectious complications (1 episode of peritonite/30 months) and the rate of drop-out during the study was 37.7%, with an annual average of 13.3%. The more difficult goal to be achieved is the hemoglobin, especially in diabetic patients and arising from hemodialysis. The main cause of drop-out was death (21%), being the cardiovascular diseases the most prevalent (40%). Age, diabetes mellitus, cardiovascular disease were among the main factors related to mortality and failure of the technique. It was seen a positive direct relationship of mortality when the general population was compared with patients on peritoneal dialysis. Furthermore, we observed marked regional differences in the rates and reasons for dropouts of patients in the different regions of the country. It was also seen the existence of the "reverse epidemiology" of obesity in these patients. In conclusion, our study allowed us to outline an epidemiological profile of peritoneal dialysis in Brazil and confirm the good quality of PD that is offered to our patients when compared to developed European countries, despite of the selection bias at the choice of TRS.

Les objectifs sont d’évaluer l’efficience (survie, qualité de vie et le coût) des deux techniques de dialyse de rechercher les déterminants qui orientent le choix vers l’une ou l’autre des techniques de dialyse et d’évaluer le parcours de soins des patients en dialyse. La première partie de ce travail de thèse à analyser les données de la région PACA issues du registre REIN. Cette analyse est descriptive et porte sur le profil des patients démarrent un traitement en dialyse (HD et DP). Une analyse de survie a été réalisée selon la technique de dialyse initiale et selon le parcours de soins. Dans une seconde partie, le coût et sur la qualité de vie ont été évalués selon les différentes techniques de dialyse afin d’évaluer l’efficience de ces modalités à partir des données recueillies dans un PHRC régional. Dans une troisième partie, les facteurs liés au choix initial de la technique de dialyse, DP ou HD ont été recherchés. Ce travail a fait l’objet d’une étude ciblée auprès de patients et de néphrologues au sein de 4 structures de dialyse. La survie et la qualité de vie des patients sont similaires entre HD et DP. Le changement de technique, de la DP vers l'HD, a un impact positif sur la survie. La DP est moins coûteuse que l’HD. Les contre-indications médicales à la DP ne concernaient que 26,7% des patients inclus. En absence de contre-indications, la préférence du patient et les pratiques des professionnelles (information et pratiques de centre) sont les deux principaux facteurs liés au choix initial de la technique de dialyse, notamment par la DP. Une meilleure information pourrait contribuer à augmenter le choix de la DP. / The objectives of this work were to assess and compare the efficiency (survival, quality of life and cost) of patients initially treated with peritoneal dialysis (PD) or hemodialysis (HD), to search determinants that guide the initial choice towards either dialysis techniques and to assess the trajectory between dialysis modalities. The first part of this thesis was to analyze the database, from the PACA region (2004 – 2014), issue from the French REIN registry. This analysis was descriptive and focused to analyze main characteristics and outcome (survival) of dialysis patients (initial dialysis and switching) and to identify risk factors. The second part of this thesis was to measure and compare dialysis patient quality of life and health’s care costs between dialysis modalities (HD and PD). Database was issued from PHRC. The third part was to search the factors related to the initial choice of dialysis technique, PD or HD. This work was the subject of a targeted survey of patients and neurologists in a dialysis structure. The survival and the quality of life were similar between hemodialysis and peritoneal dialysis. Switching to HD may improve positively the survival compared to those who remained on PD, whereas, switching to PD was not. The DP is less expensive than HD. Medical contraindications to the PD were for 26.7%. In the absence of contraindications, patient preference and professional practices (information and practical center) are the two main factors related to the initial choice of dialysis technique, in particular to choice of PD. Better information could help to increase the choice of DP

This thesis deals with the profitability of sales of the dialysis care provider. The main aim of the work was to optimise the dialysis care in Jindrichuv Hradec hospital. Mentioned proposed solution concerns personnel and technical aspects and particular elimination methods. Another aim of the work was to clarify the reimbursement system of the particular dialysis methods, to compare economic results with the profitability of the dialysis care in the years 2006 and 2007. The author endeavoured to create possible ways of the development based on the knowledge of the number of patients and the insurance company reimbursement system. Necessary data and information were acquired from Jindrichuv Hradec hospital reports. This work is thought to contribute to enrich the practical usage and its results can be used by the hospital management or anybody interested in the dialysis care and its economic aspects.

Introduction: Restless Legs Syndrome (RLS) is more prevalent in chronic kidney disease patients in comparison to the general population, but its diagnosis is still delayed and predictors are unknown. Objectives: The goals of this study are to diagnose, determine the prevalence and severity of RLS and to identify independent variables associated with this disease among chronic dialysis patients. Methods: 326 chronic dialysis patients were launched in this observational and transversal study. International Study Group of Restless Legs Syndrome criterion was used to diagnosis RLS and International Scale of Degrees of Restless Legs Syndrome was used to determine its severity. Patients with and without RLS were compared using demographic and clinical characteristics, including dialysis modality. Statistical analysis was performed using Student t test and chi-square test (significance level p<0.05). Results: The median age was 50 years, 59% were men, 77% had time on dialysis >1 year and hypertension was the most common etiology (26%). RLS was diagnosed in 19.3% of patients and in 52.4% of them it was in severe forms. Patients with and without RLS were not different according to demographic, clinical and modalities characteristics. Conclusions: RLS is frequent in chronic dialysis patients and it happen in severe forms. Dialysis modality and other clinical characteristics analyzed in this sample may not have a significant effect on the diagnosis. Further studies are necessary to identify potentially predictors of RLS in this specific population. / Introdução: A Síndrome das Pernas Inquietas (SPI) possui maior prevalência em pacientes renais crônicos quando comparados à população geral, porém seu diagnóstico é tardio e seus preditores desconhecidos. Objetivos: Diagnosticar, determinar a frequência e avaliar a gravidade da SPI em renais crônicos em diálise, comparar prevalência e gravidade da SPI entre as modalidades dialíticas e identificar seus possíveis fatores preditores nesta população. Métodos: Estudo observacional e transversal com 326 pacientes em diálise, utilizando os critérios estabelecidos pelo Grupo Internacional de Estudo da SPI para o diagnóstico e a Escala de Graduação da SPI para determinação da sua gravidade. Compararam-se pacientes com e sem SPI no tocante a características clínico-demográficas e à modalidade dialítica. Realizou-se a análise estatística através dos testes t de Student e Qui-Quadrado, considerando p<0,05 para rejeição da hipótese nula. Resultados: Na amostra predominaram homens (59%), com média de idade de 50 anos, há mais de um ano em diálise (77%), tendo a nefrosclerose hipertensiva como principal etiologia (26,1%). Diagnosticou-se SPI em 19,3% dos pacientes e esta ocorreu em 52,4% deles nas formas grave ou muito grave. Pacientes com e sem SPI não diferiram no tocante às características clínico-demográficas e modalidade dialítica. Conclusões: A SPI é frequente em pacientes dialíticos e ocorre predominantemente nas suas formas mais graves, devendo ser pesquisada rotineiramente neles. Modalidade dialítica parece não exercer influência na sua ocorrência. Estudos adicionais são necessários na tentativa de identificar possíveis fatores preditores, já que as características analisadas nesta série não se associaram ao diagnóstico.

Bakgrund: Njursvikt innebär en nedsatt filtreringsförmåga och delas in i två tillstånd, akut och kronisk. Akut njursvikt utvecklas inom kort tid med kraftigt reducerad glomerulär filtration och leder till ett allvarligt tillstånd, medan vid kronisk njursvikt försämras kapaciteten långsamt under en längre tid och i det senare skedet krävs kontinuerlig dialysbehandling. Personer som drabbas av njursvikt behöver dialysbehandling för att uppehålla livet. Många väljer en behandlingsform med hembaserad dialys som innefattar både hemodialys (HD) och peritonealdialys (PD). Det krävs mycket självhantering vid utförandet av dialys i hemmet, och för att leva med sjukdomen behöver personen har förståelse för egenvård och samarbete med sjukvården.    Syfte: Att belysa personers upplevelser av att leva med hembaserad dialysbehandling vid kronisk njursvikt. Metod: Litteraturöversikten baserades på tio vetenskapliga artiklar med kvalitativa ansatser.  Artiklarna hämtades från databaserna CINAHL complete och PubMed med års begränsning 2009-2019. Resultat: Fyra teman framkom kring upplevelser att leva med dialys i hemmet: En förändrad livssituation påverkar självbild och kroppsuppfattning, Behov av stöd och hjälp vid egenvård, Upplevelser av begränsningar och anpassning och En känsla av frihet och ökad livskvalitet. Diskussion: I metoddiskussionen diskuteras styrkor och svagheter i hur studien har genomförts. Resultatet diskuteras mot Orems egenvårdteori, tidigare forskning och riktlinjer. En stor del av diskussionen understryker betydelsen av personers egenvårdsförmåga i samband med livsförändring och anpassningsprocess samt betydelsen av stöd och hjälp från sjukvården och närstående. / Background: Kidney failure includes reduced filtration ability and can be categorised into an acute and a chronic form. Acute renal failure develops within a short timeperiod and comes with a heavily reduced glomerular filtration whereas chronic kidney failure progresses slowly during a longer period of time and in the later stages, continuous dialysis treatment becomes necessary. Individuals afflicted by renal failure need dialysis treatment to survive. Many people choose a home-based dialysis including both haemodialysis and peritoneal dialysis. Home -based dialysis necessitates much individual efforts and to live with the disease there is a need for understanding selfcare as well as collaborating with national health care. Aim: To review individual experiences from living with home-based dialysis with chronic renal failure. Method: A literature review was based on ten scientific articles with qualitative methodology. The articles were obtained from the databases CINAHL complete and PUBMed covering 2009 to 2019. Results: Four themes associated with the experiences from living with home-dialysis emerged: A changed self - and body image, Need of support and help during selfcare, Experiences from limitations and adjustments, A sense of freedom and increased quality of life. Discussion: In the discussion on methodology, strength and weaknesses of the study is discussed. The results are discussed in the context of the self-care theory of Orem, previous research and guidelines.  A major part of the discussion underlines the importance of the self-care ability of the individual in the context of lifestyle changes and in the process of adjustment. Also the importance of support and help by the health-care system and relatives is emphasised.

Orientador: Pasqual Barretti / Resumo: A peritoniteé complicação grave e responsável pela maioria dos casos de falência da técnica de diálise peritoneal (DP). Os cocos Gram-positivos são o grupo etiológico principal, sendo os estafilococos coagulase-negativa (ECN) os germes mais comuns e o Staphylococcus aureus(S.aureus), associado a episódios mais graves e commenor frequência de resolução. O conhecimento dos fatores de risco e dospreditoresda sua evolução podem contribuir para a melhoria das estratégias de prevenção e de tratamento. Objetivo:Os objetivos do presente estudo foram avaliar os fatores de risco para o primeiro episódio de peritonite por estafilococos e os fatores associados à resolução e falência da técnica após resolução do episódio de peritonite, em uma grande coorte brasileira de pacientes em DP (BRAZPD). Métodos:De uma coorte de 5707 pacientes incidentes adultos, com mais de 90 dias de tratamento por DP, foram incluídos, entre dezembro de 2004 e novembro de 2011, aqueles que apresentaram um primeiro episódio de peritonite por S. aureus ou ECN. As covariáveis, potencialmente associadas aos desfechos, foram testadas em análise univariada e aquelas com p ≤ 0,10 incluídas no modelo multivariado. Resultados:Durante o seguimento,389pacientes apresentaram um primeiro episódio de peritonite estafilocócica. Destes, 234 foram causados por S. aureus e 155 por ECN. Os grupos que apresentaram peritonite por S. aureus ou por ECN foram semelhantes para a maior parte das características basais. Entre os pacientes... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Peritonitis is a serious complication of peritoneal dialysis (PD) and the main cause of technique failure. Gram-positive cocci are the most frequent etiological group, coagulase-negative staphylococci (CNS) are the most common germs, and Staphylococcus aureus (S. aureus) is associated with more severe episodes and lower resolution rate. Objective: The objectives of this study were to evaluate the risk factors for the first episode of staphylococcal peritonitis, and the factors associated with resolution and technique failure after peritonitis episode resolution, in a large Brazilian cohort of PD patients (BRAZPD). Methods: From a cohort of 5707 adult incident patients with more than 90 days of PD treatment, between December 2004 and November 2011, those who had a first episode of S. aureus or CNS peritonitis were included. The covariates potentially associated with the outcomes were tested in univariate analysis and those with p ≤ 0.10 included in the multivariate model. Results: During follow-up, 389 patients had a first episode of staphylococcal peritonitis. Of these, 234 were caused by S. aureus and 155 by CNS. The groups of patients with S. aureus or CNS peritonitis were similar for most baseline characteristics. Among S. aureus peritonitis, there was resolution in 190 (81.2%); technique failure in 41 (21.6%), and episode-related death in 18 (7.7%). In the episodes by CNS, there were 127 resolutions (82.6%); 33 technique failures (25.8%), and 12 episode-related deaths (7.... (Complete abstract click electronic access below) / Doutor

Les modalités de dialyse à domicile, soit la dialyse péritonéale (DP) et l’hémodialyse à domicile (HDD), offrent plusieurs avantages aux patients avec insuffisance rénale terminale (IRT), que ce soit par rapport à la qualité de vie ou à une diminution des complications liées à l’IRT. Peu de données sont toutefois disponibles quant aux répercussions cliniques de l’initiation de la thérapie de suppléance rénale via la DP ou l’HDD et de l’optimisation subséquente du traitement à domicile. Le présent mémoire visait donc à répondre aux trois questions suivantes soit (1) la comparaison entre la survie des patients débutant la thérapie de suppléance rénale par une ou l’autre des modalités à domicile, (2) l’évaluation du modèle de dialyse à domicile intégrée (c’est la dire l’initiation de la suppléance rénale en DP avec un transfert subséquent en HDD) et (3) l’évaluation des prédicteurs dudit modèle de dialyse à domicile intégrée. L’évaluation de 11 416 patients ayant débuté la suppléance rénale en Australie et Nouvelle-Zélande entre 2000 et 2012 a montré une association entre une mortalité globale inférieure chez les patients traités par HDD comparativement à ceux traités par DP (rapport des risques [hazard ratio - HR] 0.47, intervalle de confiance [IC] de 95%, 0.38-0.59). Par contre, les patients ayant débuté la suppléance rénale en DP et ayant ensuite été transférés en HDD (modèle de dialyse à domicile intégrée) avaintt une survie en dialyse à domicile similaire à ceux directement traités par l’HDD (HR 0.92, IC de 95%, 0.52-1.62). Finalement, les caractéristiques démographiques de base (jeune âge, sexe masculin, ethnie), les comorbidités, la cause de l’insuffisance rénale terminale, la durée du traitement et la raison de l’arrêt de la DP étaient des prédicteurs du modèle de dialyse à domicile intégrée. / Treatment of end-stage renal disease with home dialysis modalities (peritoneal dialysis [PD] and home hemodialysis [HHD]) is associated with significant patient-related benefits, including improved quality of life, greater autonomy and lower rates of medical complications. Although home dialysis is being increasingly promoted internationally, little data has been published to evaluate outcomes of patients treated with PD and HDD at time of renal replacement therapy (RRT) initiation and evaluate the optimal home dialysis treatment pattern. The current project specifically aimed to answer the following questions: (1) what is the survival associated with initiation of RRT with PD or HDD, (2) what is the survival associated with the integrated home dialysis model (PD with subsequent transfer to HHD) compared to PD or HDD treatment initially, (3) what are the predictors associated with the integrated home dialysis model. The first study included 11 416 incident dialysis patients from Australia and New Zealand between 2000 and 2012. Treatment with HHD at start of RRT was associated with a lower mortality compared to initial treatment with PD (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.38-0.59). The second study assessed the integrated home dialysis model per se and showed a similar mortality among patients treated with the integrated home model (PD with transfer to HHD after PD ending) and patients treated with HHD from start of RRT (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.52-1.62). Finally, the third study assessed the predictors of the integrated home dialysis model and identified baseline characteristics such as lower age, male sex, race, cause of end-stage renal disease, comorbidities and duration of PD therapy as potential predictors of a transfer from PD to HHD.

A modificação oxidativa da LDL possui um papel crucial na patogênese da aterosclerose que é uma das principais causas de mortalidade nos pacientes renais crônicos. Uma subfração de LDL modificada in vivo, denominada LDL eletronegativa (LDL-), é formada a partir de modificações da parte protéica (ApoB100) e lipídica (fosfolípides, triglicérides e colesterol) da LDL induzidas por diversos mecanismos. A LDL (-) tem menor afinidade pelos receptores da LDL, é citotóxica para células endoteliais e apresenta atividade pró-inflamatória, quando comparada à LDL nativa. Com o objetivo de investigar as alterações do estado nutricional relacionadas à formação da LDL(-) nos pacientes renais crônicos, analisou-se neste estudo as concentrações plasmáticas de LDL(-), anticorpos IgG anti-LDL(-) e seus imunocomplexos em pacientes sob hemodiálise (HD, n=25) ou sob diálise peritoneal (DP, n=11) e indivíduos saudáveis (grupo controle, n=10), relacionando-as ao perfil lipídico e às concentrações plasmáticas de &#945;-tocoferol e ascorbato. Os resultados mostraram que a concentração de LDL(-) foi maior (p&#60;0.01) nos pacientes hemodialisados (575,6&#177;233,1&#181;g/mL) quando comparados aos pacientes submetidos à diálise peritoneal (223,4&#177;117,5 &#181;g/mL) e aos controles (54,9&#177;33,3&#181;g/mL). Os níveis de anticorpos IgG anti-LDL(-) foram mais elevados (p&#60;0,00001) nos controles (O,36&#177;0,09&#181;g/mL), quando comparados aos pacientes DP (0,28&#177;0,12&#181;g/mL) e HD (0,2&#177;0,1 &#181;g/mL). As concentrações dos imunocomplexos no grupo controle (0,35&#177;0,20&#181;g/mL) foram significativamente maiores comparadas às dos grupos HD (0,15&#177;0,07&#181;g/mL) e DP (0,22&#177;0,07&#181;g/mL). Não houve diferença das concentrações plasmáticas de ascorbato e de alfa-tocoferol (normalizada pela concentração de colesterol) nos grupos estudados. A maioria da população estudada estava eutrófica, segundo o índice de massa corpórea (IMG). Conclui-se que as concentração de LDL(-) nos pacientes HD e DP foram significativamente mais elevadas, enquanto os níveis de anticorpos IgG anti-LDL(-) foram menores, nos pacientes HD e DP comparados ao grupo controle. As análises de correlação demonstraram que os valores de prega cutânea tricipital (PCT) se correlacionaram diretamente com as concentrações plasmáticas dos imunocomlexos (r= 0,37; p= 0,01) e inversamente com as concentrações plasmáticas de LDL(-) (r= - 0.37; p= 0,018). As concentrações plasmáticas dos anticorpos anti-LDL(-) se correlacionaram diretamente com os valores do IMC (r= 0,83 p=0,00001) e da circunferência da cintura (r= 0,75 p= 0,0001). / A minimally modified form of LDL, with structural ApoB100 modification and lower affinity by LDL receptors, has been described in blood plasma. This circulating modified form of LDL, named electronegative LDL, LDL(-), has increased negative charge, higher cytotoxicity and pro-inflammatory activity as compared to the native LDL. This LDL-is poorly described in hemodialysis and there is no study in peritoneal dialysis patients. Thus, the purpose of this study was to evaluate the relation of the nutritional status with the amount of electronegative LDL (LDL-), its autoantibodies and immune complexes (IC) in dialysed patients. LDL(-), its autoantibodies and IC were determined by ELISA in chronic kidney disease (CKD) patients undergoing hemodialysis (HD) or peritoneal dialysis (PD) and compared to subjects without CKD (controls). Nutritional status, lipid profile and plasma concentrations of alpha-tocopherol, ascorbate and immune complexes (IC) were also evaluated. Results are expressed as median of LDL-(&#181;g/mL) and anti-LDL(-) IgG (OD405 nm). The concentrations of LDL(-) were higher in HD patients (575.6&#177;233.1 &#181;g/mL) as compared to PD (223.4&#177;117.5&#181;g/mL) and control groups (54.9&#177;33.3&#181;g/mL) (p&#60;0.01). The anti-LDL(-) IgG auto-antibodies were elevated in controls (0.36&#177;0.09&#181;g/mL) in relation to PD patients (0.28&#177;0.12&#181;g/mL) and HD patients (0.2&#177;0.1 &#181;g/mL) , (p&#60;0.00001). A negative correlation was observed between anti¬-LDL(-)lgG and LDL(-) levels (r = -0.43; P = 0.003) in the studied groups. The concentrations of le in the control group (0.35&#177;0.20&#181;g/mL) were higher compared with HD (0.15&#177;0.07&#181;g/mL) and PD (0.22&#177;0.07&#181;g/mL) groups. No differences were found for the plasma levels of ascorbate and alpha-tocopherol (normalized by cholesterol concentration) among the studied groups The body mass index (BMI) was normal in the majority of the studied subjects. The highest LDL(-) concentrations were found in HD patients, and for the first time, we showed that PD patients also have high levels of LDL(-) when compared with non-CKD subjects. The levels of anti-LDL(-) IgG in CKD patients were lower compared to controls. The correlation analysis showed that the values for triceps skin fold were positively correlated with blood plasma concentrations of IC (r= 0.37; p=0.01) and negatively correlated with LDL(-) concentrations (r= - 0.37; P 0.018). The concentrations of anti-LDL(-) autoantibodies were directly ·correlated with BMI (r= 0.83 p=0.00001) and waist circunference (r= 0.75 p= 0.0001).