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<p>We defined hypertension in pregnancy as a composite of gestational hypertension, preeclampsia and eclampsia. The etiology of hypertension in pregnancy remains controversial. The three chapters of this thesis explore the risk of hypertension in pregnancy from various kidney conditions. Chapter 1 introduces the reader to the thesis. Chapter 2 is a systematic review that studied the risk of developing hypertension in pregnant women with chronic kidney disease but not on dialysis. We found that women with chronic kidney disease had at least a twofold higher relative risk of developing hypertension during pregnancy compared with women having no chronic kidney disease. Chapter 3 is a retrospective study looking at the risk of developing gestational hypertension and preeclampsia in women who had symptomatic gastroenteritis after drinking water infected with <em>E. coli</em> O157:H7 during the Walkerton outbreak in May 2000. We conducted this study using linked datasets at the Institute of Evaluative Sciences (ICES) Toronto, Ontario. We observed that there was no increased risk of developing gestational hypertension or preeclampsia among the symptomatic women compared with women from the neighbouring towns who were asymptomatic or did not drink the water. Chapter 4 is a protocol of a prospective cohort study recruiting female kidney donors and healthy non-donors as the comparative group to study pregnancy outcomes in these individuals. This is a multicentre study involving 12 transplant centres throughout Canada. There are 59 participants in this study to date (Feb 28, 2013) of which seven have been pregnant so far. Data collection for this study is ongoing.</p> / Doctor of Philosophy (PhD)

Problématique. La Fondation Canadienne du rein soutient qu’en 2013, la prévalence de l’insuffisance rénale chronique (IRC) avoisinait les 10% et qu’elle touchait une proportion considérable de gens souffrant d’obésité. Il semble raisonnable de viser une perte pondérale modérée chez les gens atteints du duo obésité – IRC. Malgré cela, aucune recommandation nutritionnelle n’est spécifiquement bâtie afin de respecter les restrictions alimentaires liées à l’IRC et aux autres co-morbiditées, tout en permettant un déficit énergétique. Objectifs. Ce projet de recherche vise à étudier les facteurs associés avec la réussite d’une perte de poids dans le contexte restreint de ces patients. Méthodologie. 45 patients en évaluation ou en attente d’une transplantation rénale seront recrutés à la clinique de greffe rénale de l’Hôpital Maisonneuve-Rosemont. Une entrevue sera menée afin de compléter deux questionnaires (valeurs biochimiques, anthropométrie, historique médical, habitudes de vie, contexte sociodémographique, comportement alimentaire) suivie de la remise d’un journal alimentaire de quatre jours. Les apports nutritionnels obtenues seront analysés et comparés aux lignes directrices actuelles. Résultats. La perte de poids est difficile et limitée, chez les gens obèses souffrant d’IRC, malgré l’atteinte des cibles caloriques estimées et le niveau de motivation élevé de ceux-ci. Discussion. La sédentarité (46,7%, actif ˂ 1 hr/ jr) et le peu de suivi en nutrition pourraient entraver l’atteinte du poids ciblé. Conclusion. L’échec observé dans la perte pondérale semble principalement lié à la sédentarité alors qu’il n’y aurait aucune influence directe de l’apport calorique, du manque de motivation ou des comportements alimentaires. / Problematic. The Kidney Foundation of Canada argues that in 2013, the prevalence of chronic kidney disease (CKD) was around 10% and it touched a considerable proportion of people suffering from obesity. It should be reasonable to consider moderate weight loss in these patients. Despite this, no nutritional recommendation is specifically built to meet the dietary restrictions related to CKD, while allowing an energy deficit. Objectives. The objective of this project is to establish the nutritional profile of the population of obese renal failure patients, while identifying the risk factors associated with weight loss before renal transplantation. Methodology. 45 patients identified during the evaluation process or who were awaiting a kidney transplant and recruited from the kidney transplant clinic of the Maisonneuve-Rosemont hospital. Their medical and nutritional profiles were evaluated by questionnaires filled during a short interview (biochemical profile, vital signs, medical history, socio-demograpic data, anthropometry, food habits). Finally, a four-day food diary, accompanied with pictures if feasible, were used to compare to the nutritional guidelines, depending on the stage of renal disease and ongoing treatment. Results. Weight loss is difficult and limited in obese people with CKD, despite achieving targets estimated calorie and their high level of motivation. Discussion. A sedentary lifestyle (46,7%, actives ˂ 1 hr/ jr) and inadequate nutritional follow-up could hinder the achievement of the target weight. Conclusion. The failure observed in weight loss seems mainly related to a sedentary lifestyle then there would be no direct impact of caloric intake, lack of motivation or eating behaviors.

L’insuffisance rénale chronique (IRC) se définit par un défaut de filtration glomérulaire et est associée à plusieurs désordres. La perturbation de l’homéostasie glucidique en fait partie. L’homéostasie glucidique est contrôlée principalement par l’insuline, soit l’hormone sécrétée en réponse au glucose par les cellules bêta-pancréatiques contenues dans les îlots de Langerhans. La préservation de la fonction de la cellule bêta est essentielle au maintien de l’homéostasie glucidique. Il a été démontré que la sécrétion de l'insuline est altérée au cours l'IRC, cependant les mécanismes demeurent peu connus. Au cours de l’IRC, l’accumulation chronique de toxines urémiques pourrait contribuer à la défaillance de la cellule bêta. L’urée est une toxine urémique majeure et sa toxicité a été récemment rapportée dans plusieurs tissus. Le but de ce mémoire était donc de vérifier le rôle de l’urée dans la dysfonction de la cellule bêta-pancréatique au cours de l’IRC. Nous avons démontré que l’exposition des îlots de souris à des concentrations pathologiques d’urée entraîne une diminution de la sécrétion d’insuline via l’augmentation du stress oxydant et des O-glycosylations. Ce défaut est dû à une perturbation du métabolisme intracellulaire du glucose. Entre autres, nous avons observé une baisse de la glycolyse associée à la réduction de l’activité enzymatique de la phosphofructokinase-1. Ces résultats démontrent un effet toxique direct de l’urée sur la sécrétion d’insuline et permettent de mieux comprendre le mécanisme de dysfonction de la cellule bêta-pancréatique au cours de l’IRC. / Chronic kidney disease (CKD) is defined as a glomerular filtration defect and is associated with many disorders. Impaired glucose homeostasis is one of them. Glucose homeostasis is maintained in part by insulin, which is the hormone secreted by the pancreatic beta cells from the islets of Langerhans in response to glucose. The preservation of beta cell function is essential to maintain glucose homeostasis. It has been demonstrated that insulin secretion is altered during CKD; however, the underlying mechanisms remain unknown. In CKD, chronic accumulation of uremic toxins could contribute to beta cell dysfunction. Urea is a major uremic toxin and its toxicity has been recently reported in many tissues. The purpose of this master project was to ascertain the role of urea in pancreatic beta cell dysfunction during CKD. We have demonstrated that exposure of mouse islets to pathological concentrations of urea leads to diminution of insulin secretion via an increase in oxidative stress and O-glycosylation. This defect is due to disturbed intracellular glucose metabolism. Among others, we have observed a reduction in glycolysis associated with a decrease in the activity of phosphofructokinase-1. These results demonstrate a direct toxic effect of urea on insulin secretion and contribute to a better understanding of mechanisms of pancreatic beta cell dysfunction during CKD.

La sténose de l’artère rénale (SAR) est à l’origine d’une néphropathie dite « ischémique », dont les mécanismes conduisant au développement d’une insuffisance rénale sont mal connus. Il est utile de savoir à partir de quel degré de SAR surviennent des modifications hémodynamiques significatives dans le rein d’aval, et si une SAR chronique et hémodynamiquement significative peut entraîner une hypoxie rénale. Nous avons donc entrepris 2 études afin de préciser le lien entre degré de SAR et baisse du débit sanguin rénal (DSR), et de rechercher l’apparition d’une hypoxie dans le rein situé en aval d’une SAR chronique. Les résultats de la première étude montrent que la baisse du DSR reste modeste tant que le degré de SAR n’a pas dépassé 70%. Ces résultats nous permettent de conclure qu’une SAR de degré inférieur à 70% n’est probablement associée qu’à des modifications hémodynamiques mineures dans le rein d’aval. Dans la deuxième étude, nous avons décrit l’évolution du contenu rénal en oxygène (CRO) sur une période de 4 semaines après induction d’une SAR chez des rats. La méthode utilisée était l’IRM BOLD, qui permet d’étudier le CRO de manière non-invasive en mesurant le paramètre R2* dont la valeur est inversement proportionnelle au CRO. La mesure hebdomadaire de R2* dans le cortex, la médullaire externe et la partie externe de la médullaire externe des reins sténosés et des reins controlatéraux ne variaient pas au cours de l’étude, malgré l’apparition progressive d’une atrophie des reins en aval de la SAR. Ces données tendent à montrer qu’il n’y a pas d’hypoxie rénale dans notre modèle, et que l’atrophie rénale observée n’est donc pas secondaire à l’hypoxie / Renal artery stenosis (RAS) can lead to a so-called “ischemic” nephropathy but the mechanisms responsible for the development of chronic kidney disease in kidney downstream the RAS are largely unknown. There is an interest to know the degree of RAS that involves significant hémodynamic changes in the downstream kidney and if hypoxia occurs in this case. Therefore, we have undertaken two studies in order to describe the link between RAS degree and renal blood flow (RBF) and to search for the development of renal hypoxia in kidney downstream the RAS. Findings of the first study were that only a minor decrease of RBF occurs until the RAS degree reach 70%. We can thus conclude from these results that RAS degree must be at least of 70% to have hemodynamical repercussions in downstream kidney. In the second study, we describe the evolution of renal oxygen content (ROC) before and during 4 weeks after the constitution of RAS. ROC was measured weekly by the MRI BOLD technique, who allows to study ROC non-invasively by measuring the parameter called R2* that is inversely proportional to ROC. The value of R2* in the cortex, the outer medulla and the outer stripe of outer medulla in stenotic kidneys and controlateral kidneys was unchanged instead the development of atrophy of the kidney downstream the RAS. These results suggest that no renal hypoxia occur in this model and that renal atrophy is not caused by hypoxia

A infecção pelo herpesvírus humano tipo 8 (HHV-8) tem sido associada ao sarcoma de Kaposi (SK) iatrogênico, que acomete pacientes imunossuprimidos e/ou transplantados renais. Em populações consideradas saudáveis, a soroprevalência para o HHV-8 varia de 1% a 8%. O presente trabalho buscou: determinar a prevalência e os títulos de anticorpos anti-HHV-8 em pacientes com insuficiência renal crônica (IRC), submetidos ou não à terapia renal substitutiva (TRS) do Hospital do Rim e Hipertensão e Casa da Diálise da UNIFESP e da Santa Casa de Misericórdia de São Paulo e, comparar os resultados obtidos com outras populações da mesma região geográfica, porém de outras categorias de risco para adquirir doenças infecciosas. Soros de 805 pacientes: 295 em hemodiálise, 54 em diálise peritoneal e 456 em acompanhamento ambulatorial, sem TRS, foram testados quanto à presença de anticorpos anti-HHV-8, de fase latente e lítica da replicação viral, por meio de técnicas de imunofluorescência indireta (IFI) LANA e Lítico, padronizadas na Seção de Imunologia do Instituto Adolfo Lutz. Os resultados obtidos foram analisados em relação a dados clínicos, epidemiológicos e laboratoriais usando o teste do qui-quadrado ou exato de Fisher para as variáveis categóricas e os testes de Mann Whitney ou Kruskal Wallis para as variáveis contínuas. Foi encontrada soropositividade ao HHV-8 em 18,0% dos pacientes com IRC, dos quais 18,3% nos pacientes em TRS e 17,7% nos pacientes sem TRS, não havendo diferença significante entre os grupos. As variáveis que estiveram relacionadas à sorologia positiva ao HHV-8 foram: transplante prévio (p<0,001) e doenças sexualmente transmissíveis (p=0,003), com destaque para a sífilis (p=0,021). As demais variáveis não mostraram associação estatística embora tenha havido maior número de amostras HHV-8 soropositivas com o avançar da idade. Em relação ao tipo e ao título de anticorpos detectados, houve mais amostras com sorologia positiva para anticorpos Lítico e maiores títulos de anticorpos LANA. A comparação dos resultados dos pacientes com IRC e outras populações de São Paulo revelou taxa semelhante de prevalência de anticorpos anti-HHV-8 na população com HIV/Aids (20,4%), considerada de alto risco para esta infecção viral. Por outro lado, a prevalência detectada na população com IRC (18,0%) foi inferior às obtidas em pacientes com SK epidêmico (89,3%), SK clássico (100,0%) e SK endêmico (87,5%), e superior a outras populações sem SK: pacientes com deficiência mental e/ou física (1,6%) e profissionais da área da saúde (1,1%). Em todos os grupos analisados houve maior número de amostras com sorologia positiva para HHV-8 de fase lítica, e maiores títulos de anticorpos LANA, exceção feita aos profissionais da área da saúde. Maiores títulos de anticorpos LANA foram detectados nos pacientes com SK. Não foram encontradas outras associações significantes. Os resultados obtidos permitem concluir que os pacientes com IRC têm alta prevalência de anticorpos anti-HHV-8, comparável aos indivíduos com HIV/Aids dessa região geográfica. Ainda, sugerem que se devam acompanhar os pacientes HHV-8 soropositivos com vistas a monitorar os títulos de anticorpos LANA e verificar se estes têm valor prognóstico. Caso isto venha a ser confirmado, sugere-se a introdução da sorologia para o HHV-8 na bateria de exames do pré-transplante renal. / Human herpesvirus 8 (HHV-8) infection is frequently associated with Kaposi\'s sarcoma (KS) in immunodeficient and renal transplanted patients. The HHV-8 seroprevalence in healthy populations varies from 1% to 8%. The present study aimed to determine the HHV-8 seroprevalence and antibodies titers in chronic kidney disease (CKD) patients with or without substitutive kidney therapy (SKT) attended at Hospital do Rim e Hipertensão and Casa da Diálise of UNIFESP, and at Santa Casa de Misericórdia de São Paulo. Secondarly, to compare the serological results with those obtained from populations of the same geographic region, presenting other risk factors for acquiring infectious diseases. Serum samples were collected from 805 CKD patients: 295 under hemodialysis, 54 under peritoneal dialysis, and 456 in ambulatorial assistance without SKT. Latent and Lytic HHV-8 antibodies were searched using indirect immunofluorescence assays that were standardized at Immunology Department of Instituto Adolfo Lutz. Chi-Square test and/or Fisher\'s exact test were performed for comparing categorical variables including epidemiological, clinical and laboratorial data, and HHV-8 serum status. Continuos variables associated with HHV-8 antibodies titers were compared using Mann Whitney or Kruskal Wallis tests. An overall HHV-8-seropositivity of 18.0% was detected in CKD patients: 18.3% in patients under SKT and 17.7% in patients without SKT. Since no difference was detected in HHV-8-seropositivity among patients, they were considered as a unique group for subsequent analysis. A strong association between HHV-8-seropositivity and previous transplant was detected (p<0.001), along with an association with others sexually transmitted diseases (p=0.003), with emphasis for syphilis (p=0.021). In addition, no other data was associated with HHV-8-seropositivity, although higher proportions of HHV-8-seropositivity were detected in samples from elderly persons. In addition, more HHV-8 Lytic antibodies positive samples, and higher titers of LANA antibodies were detected. HHV-8 seroprevalence obtained from CKD patients was similar to the HHV-8 prevalence detected among HIV/Aids patients (20.4%), who were considered a high-risk group for this viral infection. On the other hand, the HHV-8 seroprevalence of CKD patients (18.0%) was lower than the prevalence of patients with epidemic KS (89.3%), classic KS (100.0%) and endemic KS (87.5%), and higher than the patients with mental and/or physical deficiency (1.6%) and health professionals (1.1%). All analyzed groups had more HHV-8-seropositive samples for Lytic antibodies and higher titers of LANA antibodies, with exception for the health professionals. The highest LANA antibodies titers were found among KS patients groups. No other association was found. In conclusion, the obtained results points out CKD patients as a high prevalent population for HHV-8 infection, similar to HIV/Aids patients from the same geographic area. As far, it suggests that HHV-8 seropositive CKD patients should be followed up in order to verify whether LANA antibodies titers have prognostic value. In confirming this hypothesis, it may propose to include the use of HHV-8 serology in the screening testing in kidney pre-transplant.

INTRODUÇÃO: O distúrbio mineral e ósseo (DMO) contribue significativamente para a redução da sobrevida em pacientes em terapia renal substibutiva (TRS). Os artigos que tratam do assunto, em sua grande maioria, envolvem pacientes submetidos a hemodiálise (HD) e essas publicações embasam as principais diretrizes (Kidney Disease Outcomes Quality Initiative - KDOQI - e o Kidney Disease: Improving Global Outcomes - KDIGO). MÉTODOS: Utilizamos a base de dados do Brazilian Peritoneal Dialysis (BRAZPD), estudo multicêntrico prospectivo, observacional, que avaliou pacientes em diálise peritoneal (DP), entre dezembro de 2004 e janeiro de 2011. Dos 9905 pacientes incluídos nessa base, selecionamos 844 que apresentavam dados demográficos, clínicos e laboratoriais completos e tempo em DP superior a 6 meses. Esse grupo de pacientes foi avaliado no seguimento de 24 meses. As variáveis de confusão foram corrigidas por modelos estatísticos (Cox e competing risk) e os níveis séricos de cálcio (Ca), fósforo (P) e paratormônio (PTH) relacionados com a sobrevida dos pacientes. RESULTADOS: Encontramos níveis menores de relative hazard quando os pacientes apresentavam valores de Ca e P próximos a 9,7 e 5,0 mg/dL, respectivamente. Encontramos significância estatística ao associar os níveis de Ca categorizados, conforme a orientação do KDIGO (Ca: 8,4 - 10,2 mg/dL, p = 0,03), e a sobrevida. Da mesma forma foi encontrada associação entre os níveis de P e a sobrevida dos pacientes, categorizados segundo as recomendações do KDOQI e KDIGO (P: 3,5 - 5,5 mg/dL, p < 0,01, para ambos). Outros limites de Ca (8,6 - 10,3 mg/dL, p < 0,01) e P (3,5 - 6,7 mg/dL, p < 0,01), encontrados nesse estudo, mostraram risco adicional. Apesar dos pacientes com níveis de PTH próximos a 532 pg/mL apresentarem menor relative hazard, não encontramos diferença significativamente estatística para sobrevida quando categorizados para valores de PTH tanto conforme o KDOQI (150 - 300 pg/mL) quanto para o KDIGO (150- 600 pg /mL). CONCLUSÕES: Em conclusão, manter os níveis de Ca conforme as orientações do KDIGO e P conforme orientações das duas diretrizes mostraram-se eficazes para melhora da sobrevida. Valores de Ca e P, propostos por esse estudo, evidenciaram risco adicional quando os valores ultrapassaram 8,6 - 10,3 mg/dL e 3,5 - 6,7 mg/dL, respectivamente. Os níveis de PTH não se associaram a sobrevida, mesmo quando dentro dos limites recomendados pelas duas diretrizes / INTRODUCTION: Mineral and bone disorders (MBD) contribute significantly to reduced survival of patients on dialysis. The main guidelines, Kidney Disease Outcomes Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO), related to the subject, were based upon the mostly in articles involving hemodialysis patients. The aim of our study was to analyze calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) as predictors of survival in the Brazilian Peritoneal Dialysis II (BRAZPDII) cohort. METHODS: We used the Brazilian Peritoneal Dialysis II (BRAZPDII) database, an observational multi-centric prospective study, which assessed patients on Peritoneal Dialysis (PD) between December 2004 and January 2011. Amongst 9,905 patients included in this base, we selected 844 who presented complete demographic, clinical and laboratory data as well as 6 months on PD. This group of patients was followed up for 24 months. The confounding variables were included in multivariate models (Cox and competing risk), serum levels of Ca, P and PTH were the variables of interest and associated with patients\' survival on PD. RESULTS: Ca and P presenting improvements association with relative hazard when the values close to 9.7 and 5.0 mg/dL, respectively. We found a significant association between the levels of calcium, categorized by KDIGO (Ca: 8.4 - 10.2 mg/dL), and survival (p = 0.03), likewise, a compelling association between levels of P, categorized by both guidelines (KDOQI and KDIGO - P: 3.5 - 5.5 mg/dL, p < 0.01). Other ranges of Ca, (8.6 - 10.3 mg/dL, p < 0.01) and P (3.5 - 6.7 mg/dL, p < 0.01), which were proposed in this study, have shown additional risk. In spite of patients with PTH levels close to 532 pg/mL show better survival, we found no significant statistical association values of PTH categorized according to both guidelines, KDOQI (150 - 300 pg/mL) and KDIGO (150 - 600 pg/mL). CONCLUSION: In conclusion, the ranges levels of Ca proposed by KDIGO and P proposed by the both guidelines, and based in hemodialysis patients studies, has improved survival also in patients on PD. Higher levels of Ca and P have shown additional risk. Despite PTH being in the limits recommended in both guidelines, they were not associated with survival

A doença renal crônica (DRC) se associa com a hiperatividade dos sistemas nervoso simpático e renina-angiotensina-aldosterona, o que leva e aumento da pressão arterial. O exercício aeróbico pode ser utilizado para prevenir as doenças cardiovasculares associadas à DRC, em especial a hipertensão arterial porque uma única sessão de exercício aeróbico promove redução da pressão arterial após a sua execução e esse fenômeno é denominado hipotensão pós-exercício. Este efeito do exercício é mediado pela redução da atividade nervosa simpática periférica e diminuição da atividade do sistema renina-angiotensina-aldosterona. Entretanto, a presença de polimorfismos do gene da enzima conversora de angiotensina I (ECA) pode modificar a resposta aguda ao exercício aeróbico. Outro benefício descrito do exercício é seu efeito anti-inflamatório observado pela redução de marcadores inflamatórios cuja presença na DRC é marcante. Desta forma, este estudo avaliou o efeito de uma sessão de exercício aeróbico na pressão arterial, na variabilidade da frequência cardíaca e nos marcadores inflamatórios em pacientes com DRC no estágio 3, portadores de polimorfismo do gene da ECA. Para isso, 12 pacientes com DRC (estágios 3A e 3B) e 12 indivíduos saudáveis realizaram duas sessões experimentais conduzidas em ordem aleatória de exercício aeróbico (cicloergômetro, 45 min, 50% VO2pico) e repouso (repouso sentado no cicloergômetro por 45 min). Antes e após as sessões foi coletada amostra de sangue para a análise dos marcadores inflamatórios, foi registrada a variabilidade da frequência cardíaca e da pressão arterial (Finometer) e a pressão arterial. Para a análise estatística dos dados, a normalidade da distribuição foi testada pelo teste de Shapiro-Wilk e transformações matemáticas foram feitas quando necessário. Os dados foram comparados através do teste T de Student para amostras repetidas e não repetidas e pela ANOVA de dois fatores, utilizando-se como pós-teste de contraste o teste de Newman-Keuls. O exercício promoveu maior redução da PAS no grupo com DRC (-14 ± 7 vs. -4 ± 1 mmHg), na PAD o resultado foi semelhante, no qual o grupo com DRC apresentou reduções maiores que o grupo controle (-4 ± 4 vs -1 ± 1 mmHg). A FC não apresentou diferença significativa nos dois grupos pós exercício (5 ± 3 vs. 9 ± 7 bpm). As variáveis hemodinâmicas não foram diferentes entre os portadores das variações DD e II. O exercício promoveu modulação autonômica cardíaca semelhante nos dois grupos, na BFR-R e AFR-R os resultados foram semelhantes (69 ± 13 vs. 74 ± 16 un) (28 ± 20 vs. 19 ± 12 un). A variância total apresentou aumento pós exercício nos dois grupos (884 ± 837 vs. 3139 ± 2521 ms²). A modulação vasomotora (BFPAS) aumentou nos dois grupos (14 ± 4 vs. 43 ± 36) e a sensibilidade barorreflexa reduziu nos dois grupos após o exercício. Os genótipos não influenciaram as respostas neurais. Entre os marcadores inflamatórios, o TNF-alfa pós-exercício se manteve inalterado nos dois grupos estudados, mantendo apenas a diferença encontrada no pré (7,62 ± 1,21 vs. 5,59 ± 0,96). Houve redução da IL-6 nos dois grupos, porém a redução foi maior no grupo com DRC, aproximando-se dos níveis do grupo controle (1,9 ± 0,4 vs. 1,51 ± 0,45). Houve aumento da IL-10 nos dois grupos no período pós exercício, porém sem diferença significativa entre si. Não houve interação entre as variantes genotípicas e as respostas dos marcadores inflamatórios ao exercício. Concluímos que o exercício aeróbico agudo reduziu os níveis de pressão arterial de forma mais efetiva no grupo com DRC, melhorou a modulação autonômica cardíaca, reduziu as concentrações de marcadores pró-inflamatórios e aumentou as concentrações de marcadores anti-inflamatórios nos pacientes com DRC. Os polimorfismos genotípicos não influenciaram as respostas das variáveis estudadas / Chronic kidney disease (CKD) is associated with hyperactivity of the sympathetic nervous system and renin-angiotensin-aldosterone, which leads to increased blood pressure. Aerobic exercise can be used to prevent cardiovascular diseases associated with CKD, especially arterial hypertension because a single aerobic exercise session promotes blood pressure reduction after its execution and this phenomenon is called post-exercise hypotension. This effect of exercise is mediated by the reduction of peripheral sympathetic nerve activity and decreased activity of the renin-angiotensin-aldosterone system. However, the presence of angiotensin I converting enzyme (ACE) gene polymorphisms may modify the acute response to aerobic exercise. Another benefit of exercise described is its anti-inflammatory effect observed by the reduction of inflammatory markers whose presence in CKD is marked. Thus, this study evaluated the effect of an aerobic exercise session on blood pressure, heart rate variability and inflammatory markers in stage 3 CKD patients with ACE gene polymorphism. To do this, 12 patients with CKD (stages 3A and 3B) and 12 healthy subjects performed two experimental sessions conducted in a random order of aerobic exercise (cycle ergometer, 45 min, 50% VO2peak) and rest (sitting on cycle ergometer for 45 min). Before and after the sessions a blood sample was collected for the analysis of inflammatory markers, the variability of heart rate and blood pressure (Finometer) and blood pressure were recorded. For the statistical analysis of the data, the normality of the distribution was tested by the Shapiro-Wilk test and mathematical transformations were done when necessary. The data were compared by Student\'s t test for repeated and non-repeated samples and by two-way ANOVA, using the Newman-Keuls test as contrast test. The exercise promoted a greater reduction of SBP in the group with CKD (-14 ± 7 vs. -4 ± 1 mmHg), in the DBP the result was similar, in which the group with CKD presented reductions larger than the control group (-4 ± 4 vs -1 ± 1 mmHg). HR did not present a significant difference in the two post exercise groups (5 ± 3 vs. 9 ± 7 bpm). Hemodynamic variables were not different between patients with DD and II. The exercise promoted similar cardiac autonomic modulation in both groups, in the BFR-R and AFR-R the results were similar (69 ± 13 vs. 74 ± 16 un) (28 ± 20 vs. 19 ± 12 un). The total variance presented increase after exercise in both groups (884 ± 837 vs. 3139 ± 2521 ms²). Vasomotor modulation (BFPAS) increased in both groups (14 ± 4 vs. 43 ± 36) and baroreflex sensitivity decreased in both groups after exercise. Genotypes did not influence neural responses. Among the inflammatory markers, post-exercise TNF-alpha remained unchanged in the two groups, maintaining only the difference found in the pre (7.62 ± 1.21 vs. 5.59 ± 0.96). There was a reduction in IL-6 in both groups, but the reduction was greater in the CKD group, approaching the levels of the control group (1.9 ± 0.4 vs. 1.51 ± 0.45). There was an increase in IL-10 in the two groups in the post-exercise period, but without significant difference between them. There was no interaction between the genotypic variants and the responses of the inflammatory markers to exercise. We concluded that acute aerobic exercise reduced blood pressure levels more effectively in the CKD group, improved cardiac autonomic modulation, reduced proinflammatory markers concentrations, and increased concentrations of anti-inflammatory markers in CKD patients. Genotypic polymorphisms did not influence the responses of the studied variables

Submitted by Fabricia Fialho Reginato (fabriciar) on 2015-07-08T00:02:10Z No. of bitstreams: 1 CarlaGross.pdf: 1470768 bytes, checksum: 68e5843c4e0bac8fa3dd308f573bb27f (MD5) / Made available in DSpace on 2015-07-08T00:02:11Z (GMT). No. of bitstreams: 1 CarlaGross.pdf: 1470768 bytes, checksum: 68e5843c4e0bac8fa3dd308f573bb27f (MD5) Previous issue date: 2012 / Nenhuma / Esta dissertação é composta por dois artigos, o primeiro é uma revisão sistemática da literatura e o outro é um artigo empírico. O foco de investigação foi a percepção sobre a doença renal crônica, as estratégias de enfrentamento e a adesão em pacientes em hemodiálise. No estudo I, realizou-se uma revisão sistemática da literatura internacional em relação à percepção sobre a doença e a doença renal crônica em pacientes em hemodiálise no período de 2001-2012, nas bases de dados Academic Search Premier e Medline with Full Text. Encontrou-se 17 artigos de delineamento quantitativo, que foram publicados em diferentes revistas da área da saúde e por diferentes profissionais. Os resultados apontam que o conceito de percepção sobre a doença é útil para compreensão do impacto da DRC e do tratamento em HD para a qualidade de vida desses pacientes. A percepção negativa da doença foi relacionada à não-adesão ao tratamento recomendado e tiveram relação com comportamentos de autocuidado, sintomas de depressão, qualidade de vida, mortalidade e sobrevida, e na adesão ao tratamento à Medicina Complementar e Alternativa - CAM, e às percepções negativas na não-adesão ao tratamento desses pacientes. O IPQ-R é o instrumento mais utilizado e útil para avaliar as percepções sobre a doença. Já no estudo 2, o objetivo foi investigar a relação entre as percepções sobre a doença renal crônica, as estratégias de enfrentamento e a adesão ao tratamento em pacientes em HD, e o possível poder preditivo das percepções sobre a doença e do enfrentamento para a adesão ao tratamento em hemodiálise. Participaram do referido estudo 70 pacientes adultos em tratamento hemodialítico na região do Litoral Norte do Rio Grande do Sul. Os instrumentos utilizados foram o questionário de dados sociodemográficos, ficha de dados clínicos e avaliação da adesão, questionário de percepção sobre a doença – Illness Perception Questionnaire (IPQ-R), e o questionário de estratégias de enfrentamento - Coping with Health Injuries and Problems (CHIP). Algumas dimensões da percepção da doença correlacionaram-se positivamente com algumas dimensões do enfrentamento: duração cíclica da doença e as dimensões do enfrentamento paliativo, distração e preocupações emocionais; consequências da doença e enfrentamento das preocupações emocionais; controle do tratamento e enfrentamento paliativo e instrumental; percepção emocional e enfrentamento das preocupações emocionais; e por fim, a dimensão coerência da doença correlacionou-se negativamente com o enfrentamento instrumental. As dimensões de identidade, duração cíclica e consequências da doença correlacionaram-se negativamente com a adesão percebida pelas enfermeiras, enquanto os níveis de potássio também tiveram correlação negativa com a dimensão relativa às consequências da doença. A análise preditiva mostrou que apenas a dimensão referente às consequências foi preditora da adesão percebida pelas enfermeiras (8,6% da sua variância) e dos níveis de potássio (6,7% da variância). Conclui-se que a percepção sobre as consequências da doença é uma dimensão importante de ser avaliada nos pacientes em hemodiálise para prever possíveis problemas de adesão ao tratamento. Entende-se, também, que estes resultados poderão contribuir para um melhor atendimento a esses pacientes. / This dissertation comprises two articles. First one is a systematic literature review, whereas the second is an empyrical article. The investigation focuses on chronic kidney disease perception, coping strategies and adherence in hemodialysis patients. In Study I, a systematic review of international literature on illness perception and chronic kidney disease in hemodialysis patients in the period 2001-2012 was carried out. It was done on the databases Academic Search Premier and Medline with Full Text. 17 articles were found on quantitative delineation, which were published in different health magazines by various professionals. Results indicate that the concept of illness perception is useful to understand the impact of CKD and HD treatment on these patients' quality of life. Negative perception of the disease was associated with non-adherence with the recommended treatment and was related to self care behaviour, depression symptoms, quality of life, mortality and extended survival. Negative perception was also associated with adherence with treatment by Complimentary and Alternative Medicine - CAM, and with the negative perceptions in these patients' non-adherence with the treatment. The IPQ-R is the most used and useful tool to evaluate illness perception. In study 2, the objective was to investigate the relation between chronic kidney disease perception, coping strategies and adherence with treatment in HD patients, and the possible predictive power of illness perception and coping to adherence with hemodialysis treatment. 70 adult patients in hemodialytic treatment on the North Coast of the Brazilian state of Rio Grande do Sul took part in study 2. The instruments used were the sociodemographic data questionnaire, medical chart and adherence evaluation, the Illness Perception Questionnaire (IPQ-R) and the coping strategies questionnaire - Coping with Health Injuries and Problems (CHIP). Some illness perception dimensions were positively correlated to some coping dimensions: cyclic illness duration and palliative coping dimensions, distraction and emotional worry; illness consequences and emotional worry coping; treatment control and instrumental and paliative coping; emotional perception and emotional worry coping; and last, the dimension illness coherence was negatively correlated to instrumental coping. The dimensions identity, cyclic duration and illness consequences were negatively correlated to perceived compliance by nurses, whereas potassium levels also were negatively correlated to the illness consequences dimension. Predictive analysis showed that only the dimension related to the consequences was predictive of the adherence perceived by nurses (8,6% of its variance) and the potassium levels (6,7% of the variance). In conclusion, the perception of the illness consequences is an important dimension to be evaluated in hemodialysis patients in order to predict possible problems on treatment adherence. The results can also contribute for a better approach to these patients.

Introdução: A doença renal crônica afeta de 10 a 15 % da população adulta mundial e a piora da função renal, se associa com várias complicações, tais como: desnutrição, inflamação, doenças cardiovasculares e distúrbios do metabolismo mineral. A mortalidade desses pacientes é elevada sendo de 6 a 8 vezes maior que a de indivíduos saudáveis. Cerca de 22% dos pacientes incidentes, ou seja, no primeiro ano de diálise, vão a óbito. O objetivo do presente estudo foi avaliar as características clínicas, laboratoriais de pacientes incidentes em diálise além de identificar fatores de risco que contribuíssem para a mortalidade desses pacientes. Métodos: Estudamos 424 pacientes com sinais e sintomas de uremia e indicação de tratamento dialítico admitidos no serviço de emergência do Hospital das Clínicas entre Janeiro de 2006 e Dezembro de 2012. O tempo de acompanhamento foi de um ano. Analisamos os parâmetros clínicos, tipo de via de acesso para hemodiálise, fatores de risco ligados a doenças cardiovasculares e as alterações do metabolismo mineral bem como eventos clínicos ocorridos durante o seguimento. Avaliamos a sobrevida e os fatores que influenciaram a sobrevida dos pacientes, pela curva de Kaplan-Meier e análise de regressão de Cox, respectivamente. Resultados: A média de idade foi de 50±18 anos, 58,7% eram homens e 69,1% brancos. Hipertensão arterial foi a principal etiologia da doença renal primária (31,8%) seguida de DM (29,5%). Os principais fatores de risco encontrados foram tabagismo (19,6%), dislipidemia (48,8%), doenças cardiovasculares (41%) e na admissão a maioria dos pacientes não tinha acesso vascular para hemodiálise (89,4%). Os resultados dos exames laboratoriais revelaram que a maioria dos pacientes estava anêmico (83,7%), com níveis de PCR elevados (79,9%). Os distúrbios do metabolismo mineral como hipocalcemia, hiperfosfatemia, elevação dos níveis de paratormônio e diminuição dos níveis de 25(OH) vitamina D estavam presentes em praticamente todos os pacientes. Ao término de um ano, 60 pacientes faleceram (14,1%). Esses pacientes eram significativamente mais idosos, apresentavam sinais de insuficiência cardíaca congestiva, de desnutrição, de inflamação, níveis reduzidos de 25 (OH) vitamina D, desenvolveram maior número de infecções e não tinham acesso vascular definitivo para hemodiálise. Conclusões: A avaliação conjunta de parâmetros clínicos, laboratoriais e dos fatores de risco revelou que a idade mais avançada, presença de insuficiência cardíaca congestiva, desnutrição, inflamação, deficiência de vitamina D e a falta de via de acesso para hemodiálise foram fatores preditores de mortalidade em pacientes incidentes em hemodiálise / Introduction: Chronic kidney disease affects 10-15% of the world adult population, and the worsening of renal function is associated with several complications, such as malnutrition, inflammation, cardiovascular diseases and disorders of mineral metabolism. Mortality of those patients is high and 6 to 8 times higher than that of healthy individuals. About 22% of incident patients, that is, during the first year of dialysis, will die. The aim of this study was to evaluate the clinical and laboratory characteristics of incident dialysis patients and identify risk factors that contribute to the mortality of these patients. Methods: We studied 424 patients with signs and symptoms of uremia and dialysis indication admitted to the emergency service at Hospital das Clínicas between January 2006 and December 2012. Follow-up time was one year. We analyzed the clinical parameters, type of hemodialysis access road, risk factors linked to cardiovascular diseases and changes in mineral metabolism as well as clinical events occurred during follow-up. We evaluated survival and the factors that influenced patient survival by Kaplan-Meier curves and Cox regression analysis respectively. Results: Mean age was 50 ± 18 years old; 58.7% were males and 69.1% were white. Hypertension was the main cause of primary kidney disease (31.8%) followed by DM (29.5%). Major risk factors found were smoking (19.6%), dyslipidemia (48.8%), cardiovascular disease (41%), and upon admission most patients had no vascular access for hemodialysis (89.4%). Results of laboratory tests showed that most patients were anemic (83.7%), with high CRP levels (79.9%). Disturbances of mineral metabolism such as hypocalcemia, hyperphosphatemia, elevated parathyroid hormone levels and decreased levels of 25(OH) vitamin D were present in almost all patients. At the end of a year, 60 patients died (14.1%). These patients were significantly older, had signs of congestive heart failure, malnutrition, inflammation, low levels of 25(OH) vitamin D, developed greater number of infections and had no definitive vascular access for hemodialysis. Conclusions: The joint evaluation of clinical and laboratory parameters and risk factors revealed that older age, presence of congestive heart failure, malnutrition, inflammation, vitamin D deficiency and lack of hemodialysis access road were predictors of mortality in incident patients undergoing hemodialysis