Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-05-19T13:14:47Z No. of bitstreams: 1 erichvidalcarvalho.pdf: 1373882 bytes, checksum: 6df7856fd76fddbb8e6515ca30774b77 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-19T14:45:07Z (GMT) No. of bitstreams: 1 erichvidalcarvalho.pdf: 1373882 bytes, checksum: 6df7856fd76fddbb8e6515ca30774b77 (MD5) / Made available in DSpace on 2017-05-19T14:45:07Z (GMT). No. of bitstreams: 1 erichvidalcarvalho.pdf: 1373882 bytes, checksum: 6df7856fd76fddbb8e6515ca30774b77 (MD5) Previous issue date: 2013-12-13 / Introdução: O sedentarismo é um comportamento comum entre os pacientes com doença renal crônica (DRC) em hemodiálise (HD), e está associado com desfechos clínicos negativos nesta população. Acredita-se que o transplante renal tenha potencial para alterar o estilo de vida destes pacientes tornando-os mais ativos. No entanto, o efeito do transplante sobre a atividade física não está completamente esclarecido. Os estudos sobre o tema na população de transplantados utilizaram questionários como instrumento de avaliação, não sendo identificado nenhum trabalho que aferiu objetivamente, através de acelerômetro, a atividade física nestes indivíduos. Objetivos: Avaliar objetivamente a atividade física na vida diária de pacientes transplantados renais comparando a com a de pacientes em HD e explorar a possível relação de variáveis clínicas com a atividade física. Métodos: Estudo de corte transversal que incluiu indivíduos transplantados renais há pelo menos seis meses (n=23; 48,3 ± 10,3 anos) e pacientes em HD há pelo menos seis meses (n=20; 47,3 ± 12,6 anos). O tempo gasto nas diferentes atividades ou posições (andando, de pé, sentado ou deitado) e o número de passos dados foram mensurados por um acelerômetro multiaxial durante 12 horas diurnas, em dois dias úteis consecutivos nos pacientes transplantados e em quatro dias consecutivos nos pacientes em HD. Resultados: Transplantados renais apresentaram maior tempo ativo por dia (soma dos tempos andando e em pé) que pacientes em HD (311 ± 87 vs. 196 ± 54 min/dia; p = 0,001), com maior tempo andando (106 ± 53 vs. 70 ± 27 min/dia; p = 0,008) e maior tempo em pé (205 ± 55 vs. 126 ± 42 min/dia; p < 0,001). Sessenta e cinco por cento dos transplantados foram classificados como ativos (>7.500 passos/dia) comparados com apenas 20% do grupo HD (p < 0,005). O tempo ativo se correlacionou positivamente com o tempo pós-transplante, com os níveis séricos de cálcio e hemoglobina. Conclusão: Transplantados renais são significativamente mais ativos na vida diária do que pacientes em hemodiálise e a atividade física aumenta com o tempo desde o transplante. / Background: Sedentary lifestyle is a common behavior among hemodialysis (HD) patients, and is associated with negative clinical outcomes in this population. It is believed that renal transplantation has the potential to change the way of life of these patients making them more active. However, the effect of kidney transplant on physical activity has not been thoroughly investigated. There was no study that objectively assessed physical activity in renal transplant patients using accelerometer. Objective: To evaluate the physical activity in daily life in kidney transplant recipients (KTRs) compared to HD patients and explore its relationship with clinical variables. Methods: A cross-sectional study enrolled KTRs transplanted at least six months prior the study (n=23; 48.3 ± 10.3 years) and patients undergoing HD for at least six months (n=20; 47.3 ± 12.6 years). Time spent in different activities (walking, standing, sitting, and lying down), and number of steps taken, measured by a multiaxial accelerometer used for 12 h/day on two consecutive days for KTRs and on four consecutive days for HD patients were evaluated. Results: KTRs engaged in more active time per day (sum of walking and standing time) than HD patients (311 ± 87 vs. 196 ± 54 min/day; p = 0.001), with longer walking (106 ± 53 vs. 70 ± 27 min/day; p = 0.008) and standing time (205 ± 55 vs. 126 ± 42 min/day; p < 0.001). Sixty-five percent of KTRs were classified as active (>7,500 steps/day) compared to only 20% of the HD group (p < 0.005). Active time was positively correlated with time post transplant, calcium, and hemoglobin. Conclusions: KTRs are significantly more active in daily life than HD patients, and physical activity in daily life increases with time since transplantation.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-08-09T14:18:47Z No. of bitstreams: 1 rosaliamarianuneshenriqueshuaira.pdf: 2338300 bytes, checksum: bcb856eb45dfa5fd1d7f3007ad320c2b (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-08-09T14:59:27Z (GMT) No. of bitstreams: 1 rosaliamarianuneshenriqueshuaira.pdf: 2338300 bytes, checksum: bcb856eb45dfa5fd1d7f3007ad320c2b (MD5) / Made available in DSpace on 2017-08-09T14:59:27Z (GMT). No. of bitstreams: 1 rosaliamarianuneshenriqueshuaira.pdf: 2338300 bytes, checksum: bcb856eb45dfa5fd1d7f3007ad320c2b (MD5) Previous issue date: 2017-04-20 / Introdução: As doenças crônicas são responsáveis pela maioria dos óbitos no Brasil. Entre estas se destacam a hipertensão arterial e diabetes mellitus que são as principais causas da doença renal crônica (DRC). A DRC na sua fase dialítica no Brasil representa um alto custo financeiro e impacta na qualidade de vida dos usuários, o que justifica a necessidade de um diagnóstico mais precoce e um controle na fase pré-dialítica. Em 2010 foi inaugurado o Centro Hiperdia Juiz de Fora (CHJF), que ampliou o atendimento fornecido anteriormente pelo Preverim. Este programa acompanhava apenas os doentes renais em fase pré-dialítica. Com a criação CHJF ampliou o atendimento a usuários hipertensos e diabéticos com controle metabólico inadequado. Para isso foi criado um registro eletrônico onde são gravados estes atendimentos. O uso de registros eletrônicos tem sido ampliado no mundo todo visando o acompanhamento de usuários na diálise, no entanto registros em pré-diálise são raros. O objetivo deste trabalho foi validar os dados deste registro para a utilização em pesquisas e na gestão do programa. E ao final fazer a caracterização clínica da coorte em relação ao perfil demográfico e também aos indicadores clínicos de qualidade destas três enfermidades. Material e Métodos: Inicialmente foi realizada a validação do registro. A validação de um registro eletrônico de saúde é um procedimento contínuo na programação de qualquer sistema de dados. Sabemos que podem haver ocorrências que não foram previamente definidas e que impactam na qualidade dos dados. Após realizada esta padronização, avaliamos a coorte. Trabalhamos com 63.146 registros de atendimentos de usuários do CHJF de agosto de 2010 a dezembro de 2014. Foram incluídos os usuários com mais de 18 anos com pelo menos duas consultas no ambulatório da DRC. Analisamos as seguintes variáveis: sócio-demográficos, doença de base, principais medicações, principais indicadores clínicos de controle da DRC, hipertensão arterial (HAS), Diabetes mellitus (DM). Resultados: Foram exportados, convertidos e validados dados de 1.977 usuários com tempo de acompanhamento médio de 21 meses. Destes, 51,4% eram homens, 58% tinham idade >64 anos e 81,6% estavam acima do peso. As principais medicações em uso foram: diuréticos (82,9%), Bloqueador do receptor da angiotensina (BRAT) (62%), Estatina (60,7%) e Inibidor da enzima conversora de angiotensina (IECA) (49,9%). O percentual de usuários com declínio da taxa de filtração glomerular foi de 33,7%. Em relação à hemoglobina glicada, os usuários com DRC e DM, 36% estavam dentro da meta inicial e 52,1% da final. Em relação à pressão arterial, os usuários estavam na meta na admissão em 34,3% e 49,8% ao final do acompanhamento. Conclusão: Concluímos que dados validados são de vital importância para gestores em saúde e para monitorização dos usuários. Nossa população é predominantemente idosa, obesa, usuária de polifarmácia, tem pouca escolaridade, é de baixa renda sendo, portanto, uma população vulnerável, necessitando de cuidados multiprofissionais intensivos para retardar a progressão da doença e diminuir a morbimortalidade. Ressaltamos que a taxa de filtração glomerular (TFG) apresentar-se com um delta positivo nos informa que estamos atingindo a principal meta que é retardar o início da terapia renal substitutiva e, com isto melhorar a qualidade de vida e diminuir os custos. / Introduction: Chronic diseases are responsible today for the majority of deaths in Brazil. Among these, hypertension and diabetes mellitus are the main causes of chronic kidney disease (CKD). The CKD in its dialytic phase in Brazil represents a high financial cost and impacts the quality of life of the users, which justifies the need for an earlier diagnosis and a control in the pre-dialytic phase. In 2010, the Centro Hiperdia Juiz de Fora (CHJF) was inaugurated in Juiz de Fora, MG, Brazil, which expanded the service previously provided by Prevenrim. This program was only used for pre-dialytic renal patients. With the creation of CHJF, care was added to hypertensive and diabetic users with inadequate metabolic control. For this, an electronic record was created where these visits are recorded. The use of electronic records has been expanded worldwide to track dialysis users, however pre-dialysis registries are rare. The objective of this study was to validate the data from this registry for use in research and program management. Finally, the clinical characterization of the cohort in relation to the demographic profile and clinical quality indicators of these three diseases was done. Material and Methods: The registry was validated initially. The validation of an electronic health record is a continuous procedure in the programming of any data system. We know that there may be occurrences that have not been previously defined and that impact on data quality. After this standardization, we evaluated the cohort. We worked with 63,146 records of CHJF users' consultations from August 2010 to December 2014. Users 18 years old or older with at least two visits in the CKD outpatient clinic was included. We analyzed the following variables: sociodemographic, cause of kidney disease, main medications, main clinical indicators of CKD, systemic arterial hypertension (SAH), Diabetes mellitus (DM). Results: Data from 1,977 users with mean of follow-up time of 21 months were exported, converted and validated. Of these, 51.4% were men, 58% were> 64 years of age and 81.6% were overweight. The main medications used were diuretics (82.9%), angiotensin receptor blocker (ARB) (62%), Statin (60.7%) and ACE inhibitors (49.9%). The percentage of users with a decline in the glomerular filtration rate was 33.7%. Regarding glycated hemoglobin, users with CKD and DM, 36% were within the initial goal and 52.1% of the final. Regarding blood pressure, users were on target at admission at 34.3% and 49.8% at the end of follow-up. Conclusion: We conclude that the validated data is of vital importance for health managers to monitor users. We observed that our population is predominantly elderly, obese, polypharmacy patient, has a low level of education, is low income and therefore a vulnerable population, requiring intensive multi-professional care to delay the progression of the disease and reduce morbidity and mortality. It is important to highlight that since the glomerular filtration rate (GFR) presents a positive delta, it then indicates that we are achieving the main goal: to delay the onset of renal replacement therapy, thereby improving quality of life and lowering costs.

Estudos tem demonstrado que a injúria renal aguda (IRA) pode evoluir para doença renal aguda ou crônica, principalmente quando associada à comorbidades como a hipertensão sal-dependente. Além disso, o desenvolvimento da perda de função renal é comumente associado a distúrbios mineral e ósseo. O uso de antioxidantes como a N-acetilcisteína (NAC) tem sido utilizado para prevenir a lesão da IRA, no entanto pouco se sabe sobre o uso deste medicamente em um período prolongado e os seus efeitos no metabolismo mineral e ósseo. Sendo assim os objetivos do presente estudo foram avaliar a repercussão da sobrecarga de sódio na dieta em modelo de IRA com ou sem tratamento com NAC, e observar a influência da IRA, dieta hipersódica e tratamento no metabolismo mineral e ósseo após 10 semanas de protocolo. Para isto foram utilizados ratos machos Wistar alimentados com dieta normossódica (0,5% Na - NS) ou hipersódica (3,2% Na - HS), tratados com ou sem NAC (IR NAC) (600mg/L) e submetidos à cirurgia de isquemia (45 minutos) e reperfusão renal bilateral (IR) ou Sham. Os animais foram acompanhados por 10 semanas após a cirurgia. Foram avaliadas pressão arterial caudal, função renal, metabolismo mineral e histomorfometria óssea. Os animais que sofreram IR e foram alimentados com dieta HS apresentaram maior excreção de sódio, cálcio e fósforo e albuminúria. A albuminúria correlacionou-se com o aumento do PTH induzindo a um maior tecido osteoide e superfície de osteoblastos nestes animais. A NAC diminuiu excreção de sódio, cálcio, fósforo, albuminúria e PTH, mas causou a diminuição do volume ósseo e aumento da separação trabecular. A ingestão do sódio influenciou nos níveis séricos altos de 1-25(OH)2D e baixos de FGF-23. Estes resultados sugerem que a sobrecarga de sal na dieta causou evolução da IRA após 10 semanas. Essa perda de função renal aumentou o PTH, volume osteoide e osteoblastos. Em contrapartida, o tratamento com a NAC preveniu a progressão da disfunção renal, mas levou à perda de massa óssea / Studies have shown that acute kidney injury (AKI) can progress to acute or chronic kidney disease especially when associated with co-morbidities such as salt-dependent hypertension. In addition to impairment of renal function there is association with mineral and bone disorders. The antioxidants such as N-acetylcysteine (NAC) has been used to prevent the AKI; however; the prolonged use and its effects in mineral and bone metabolism is not well studied. The aim of the study was to evaluate dietary sodium overload repercussion on the AKI associated to NAC treatment and to observe its effects on bone metabolism after 10 weeks. Were used Wistar rats were fed with normal sodium (0.5% NaCl - NS) or high sodium (3.2% NaCl - HS) diet and treated or not with NAC (600 mg/L) and submitted to renal ischemia (45 minutes) and reperfusion (IR) or Sham surgery. The animals were followed up for 10 weeks after surgery. We evaluated caudal blood pressure, renal function, mineral metabolism and bone histomorphometry. In our results urinary sodium, calcium, phosphorus excretion and albuminuria were higher in HS IR animals. There was a positive correlation between albuminuria and PTH leading to osteoid tissue and surface of osteoblasts augmentation in these animals. In other hand, NAC decreased sodium, calcium, phosphorus excretion, albuminuria and PTH; however, it was observed lower bone volume and higher trabecular separation. Sodium intake had an isolated effect on 1-25(OH)2D and FGF-23. These results suggest that overload salt diet caused AKI development. Loss of renal function increased PTH, osteoid volume and osteoblasts Treatment with NAC prevented renal function impairment, however it induced to bone mass loss

Bakgrund: Idag är det drygt 700 personer som väntar på en njurtransplantation i Sverige. Njurtransplantationen är en räddning från döden för många patienter som genomgår dialys behandling eller andra former av interventioner för att kunna leva ett ”normalt liv”. För att kunna erbjuda den bästa omvårdnaden bör sjuksköterskan ha en god kunskap om patienters upplevelser. Syfte: Avsikten med litteraturstudien var att belysa patienters upplevelser av att vänta på en njurtransplantation. Metod: Litteraturstudien bygger på tio vetenskapliga studier med kvalitativ metod. Kvalitetsgranskning av artiklarna och sammanställning av resultat genomfördes. Resultat: Resultaten presenteras genom två tema som omfattar patienternas upplevelser av att vänta på en njurtransplantation. Teman som valdes ut är:Osäkerhet i väntan på en njurtransplantation; Behovet av stöd från omgivningen. Slutsats: Att få en njurtransplantation innebär en chans till ett nytt liv. Den komplexa processen som en transplantation innebar framkallade många upplevelser hos patienter med njursjukdom. Vårdens insatser bör vara inriktade på att utveckla strategier och vara mer fokuserade på patienternas behov av information och kunskapsutveckling för att kunna hantera upplevelserna vid väntan på en njurtransplantation. / Background: There are currently around 700 people waiting for a kidney transplant in Sweden. Kidney transplantation is a lifesaver for many patients undergoing dialysis or other previous interventions to be able to live a “norma llife”. In order to be able to offer the best care, the nurse should have a good knowledge of patients' experiences. Aim: The purpose of the literature study was to shed light on patients´ experiences of waiting for a kidney transplant. Method: The literature study is based on ten scientific studies with a qualitative method. Quality review of the articles and compilation of results was carried out. Results: The results are presented through two themes that include patients´experiences of waiting for a kidney transplant. Themes selected are: Uncertaintyin waiting for a kidney transplant; The need for support from the environment. Conclusion: Getting a kidney transplant means a chance at a new life. The complex process involved in a transplant evoked many experiences in patients with kidney disease. Healthcare efforts should develop their strategies and be more focused on the patients´ needs for information and knowledge development in order to be able to manage the experiences while waiting for a kidney transplant.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19599号 / 医博第4106号 / 新制||医||1014(附属図書館) / 32635 / 京都大学大学院医学研究科医学専攻 / (主査)教授 柳田 素子, 教授 妹尾 浩, 教授 浅野 雅秀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Indiana University-Purdue University Indianapolis (IUPUI) / Polycystic kidney diseases (PKD) are genetic disorders characterized by fluid filled cysts in the kidney tubules and liver bile ducts. There are two forms of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). The focus of the studies in this thesis has been on ADPKD. The disease progresses slowly and the fluid-filled cysts grow in size due to increased rates of cell proliferation and fluid secretion into the cyst lumen. The expanding cysts compromise the normal kidney function and result in a decrease of renal function to the point of end-stage renal failure in midlife. Cyst enlargement is due, at least in part, to chloride secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Currently therapy is limited to renal cyst aspiration, dialysis, and eventually renal transplantation after organ failure, thus it has critical to determine possible drug therapies for the treatment of PKD. Previous studies showed that cyst fluid caused a secretory response in cells lining the cysts. We hypothesized that once the cyst have expanded and become so large that they burst or leak, which could also occur due to renal injury or aging, the cyst fluid may stimulate additional cyst growth. Lysophosphatidic Acid (LPA) was determined to be the active component of human cyst fluid, and we investigated the LPA stimulated signaling pathway. Our data suggest that the LPA stimulates chloride and fluid secretion by a combination of CFTR and Calcium-Activated chloride channels (CaCC) and that the two channels may functionally be linked to each other. The secretion is not occurring through a cAMP stimulated pathway, and it is possible that TMEM16A, a CaCC, plays a larger role than previously expected. Previous studies demonstrated that PPARγ agonists, insulin sensitizing drugs used to treat diabetes, inhibit chloride secretion by the collecting duct principal cells by decreasing CFTR synthesis. It was logical therefore to considered PPARγ agonists as long-term treatment for PKD. The first preclinical studied showed that high (20 mg/kg BW) dose pioglitazone, a PPARγ agonist, inhibited cyst growth in the PCK rat model, a slow progressing model, of PKD. To continue to look at the effects of the PPARγ agonists another preclinical study was completed, which tested if there was a class action of PPARγ agonists and if a lower dose was effective in treating the cystic burden. Using the PCK rat model, and another PPARγ agonist, rosiglitazone, a 24 week study was completed using 3 doses (4, 0.4, and 0.04 mg/kg BW). 4 mg/kg BW rosiglitazone is analogous to 20 mg/kg BW pioglitazone. The data indicated that the rosiglitazone is effective in lowering the cystic burden, and importantly the low dose proved to be effective. An additional rat model, the W-WPK rapidly progressing model was used to determine efficacy across multiple models, and to determine if there was a way to track the progress of the disease in a manner analogous to that used in human patients. The animals were treated with pioglitazone using 2 doses (2 and 20 mg/kg BW), and were imaged using CT scans to track the progress of the disease. The data suggest that pioglitazone was not as effective in the W-WPK rat model as it was the PCK rat model. There was a trend however, that low dose PPARγ agonist was as effective ad high dose. Even more important, the CT scans proved to be an effective way to track the progress of the disease in animal models.

<p>  </p> <p>This research evaluates Kidney Health Initiative's (KHI)   four kidney replacement therapy (KRT) technology priority groups in the roadmap:</p> <p>1) Literature review of technology citations for each of the four KHI priority groups for safety and efficacy data with a patient centered focus. Additionally, the incorporation and integration of KHI minimum technical design criteria in six areas into the development process.</p> <p>2) Clinical PICO analysis of the critical clinical outcomes that the discovery and innovation from the specific technology priority group addresses</p> <p>3) Critical evaluation of KRT technologies on patients with ESKD by expert clinicians and scientists in KRT through Delphi method with targeted questionnaires</p>