End-stage renal disease (ESRD), or kidney failure, is a serious illness with significant health consequences and high-cost treatment options. Since the early 1980s, the number of Canadians with ESRD has more than quadrupled (CIHI, 2001), leading to questions about the current and future impact of the disease on public health, quality of life, health spending, and patients’ productivity. Using an economic burden of illness approach, this thesis estimates ESRD’s “direct” health care costs and “indirect” costs, such as productivity losses due to premature death and short- and long-term disability. It also projects future results under various alternative assumptions using a multi-state discrete time Markov model. The analysis suggests that, although less than 0.1% of Canadians have ESRD, it generated direct health care costs of $1.3 billion in 2000 or $51,099 per person with ESRD. That compares to $3,183 per capita for Canadians overall (CIHI, 2002b). Adding indirect morbidity and mortality costs brings the total to $1.9 billion. Rising ESRD numbers suggest higher costs in the future. Further analysis explored the effect of various assumptions about drivers of past trends, such as population growth, changes in the age structure, and the prevalence of conditions known to cause ESRD (e.g. diabetes). Projections were most sensitive to assumptions about the rate at which new cases are diagnosed. If current trends continue, the total economic burden of the disease can be expected to reach $7.9 billion by 2015 (year 2000 dollars). On the other hand, if the rate of new cases in 2000 were maintained, the economic burden of illness would be $5.7 billion in 2015. Nevertheless, under this and many other assumptions, there is likely to be a significant gap between available organs for transplant and the demand for transplantation. The likely effects of various options for addressing this gap are also explored. / Thesis / Doctor of Philosophy (PhD)

Introdução: O perfil de morbidade e mortalidade no Brasil passou por uma transição demográfica, com o aumento da prevalência de doenças crônicas na população em geral, tais como diabetes mellitus (DM) e hipertensão arterial (HA), e como consequência, a doença renal crônica (DRC). Na última década, a DRC tem sido apresentada como um grande desafio para a saúde pública no Brasil e no mundo. Objetivo: O objetivo deste estudo foi identificar os fatores envolvidos na progressão da doença renal dos pacientes atendidos no Ambulatório de Uremia do HCFMRP-USP. Material e métodos: Trata-se de um estudo epidemiológico, transversal e retrospectivo de prontuários de pacientes do Ambulatório de Uremia, no período entre 2002 e 2012. Os dados foram extraídos dos registros médicos para a análise quantitativa e qualitativa. Resultados: A análise mostrou que 53% dos indivíduos eram do sexo masculino, com idade média de 61,21 anos. A mortalidade foi maior entre os idosos, que também apresentaram menor tempo de seguimento ambulatorial. A doença de base principal foi a HA (42,94%) e o tempo médio de seguimento foi de 11,23 meses. O encaminhamento para hemodiálise (44,48%) foi o desfecho clínico mais comum. Os principais fatores relacionados à progressão da DRC foram baixos níveis séricos de albumina, baixo valor de depuração da creatinina, pressão arterial não controlada e níveis séricos elevados de colesterol total. Discussão: A DRC tem aumentada progressivamente na população, especialmente entre os idosos, onde a taxa de mortalidade é maior e eles têm menos tempo de acompanhamento. As causas mais comuns das doenças de base foram HA e DM e vários fatores estavam envolvidos na progressão da doença renal. Aqueles indivíduos que tiveram DM como doença de base evoluíram mais rápido do que os outros para diálise. Conclusão: Os níveis séricos baixos de albumina, baixo valor de depuração da creatinina, pressão arterial não controlada e níveis séricos elevados de colesterol total são fatores envolvidos na progressão da doença renal, e são fatores modificáveis que através de intervenções multidisciplinares durante o tratamento conservador pode retardar a progressão da DRC para diálise. / Introduction: The profile of morbidity and mortality in Brazil has undergone a demographic transition, with increasing prevalence of chronic diseases in the general population, such as diabetes mellitus (DM) and hypertension (H), and as a consequence the chronic kidney disease (CKD). In the last decade the CKD has been presented as a major challenge for public health in Brazil and worldwide. Objective: This study aims was to identify the factors involved in the progression of renal disease of patients attending in the Outpatient Uremia of the HCFMRP-USP. Material and methods: This is an epidemiological, cross-sectional and retrospective analysis of medical records of patients of Outpatient Uremia in the period between 2002 and 2012. The data were extracted of medical records for quantitative and qualitative analysis. Results: The analysis showed that 53% of subjects were male, with a mean age of 61.21 years. Mortality was higher among the elderly, who also presented shorter time of outpatient follow-up. The main underlying disease was H (42.94%) and the mean time of follow-up was 11.23 months. The referral for hemodialysis (44.48%) was the clinical outcome more common. The main factors related to the progression of CKD were low serum albumin, low value of creatinine clearance, high blood pressure levels and high serum levels of total cholesterol. Discussion: The CKD has been progressively increasing in the population, especially among the elderly, where the mortality rate is higher and they have less time of follow-up. The most common causes of underlying disease were H and DM and several factors were involved in the progression of kidney disease. Those individuals who had DM like underlying disease evolved faster than the others to dialysis. Conclusion: Low serum levels of albumin, low value of creatinine clearance, high blood pressure levels and high serum levels of total cholesterol are factors involved in the progression of renal disease, and are modifiable factors that through multidisciplinary interventions during conservative treatment can slow the progression of CKD to dialysis.

Chronic kidney disease (CKD) is a non-communicable progressive disease that can lead to kidney failure or end-stage renal disease. In Nigeria, many people do not have access to health care due to extreme poverty, which means that those suffering from diabetes or high blood pressure, or both diseases, which have been identified as the 2 main risk factors, may not know their health status. The purpose of this phenomenological study was to explore the level of CKD awareness among Nigerians and if cultural beliefs affect individuals' health seeking behaviors because of the diverse nature of the Nigerian population. The protection motivation theory provided the framework for the study. Data were collected through semi-structured interviews with 14 participants, and data analysis included traditional coding. Findings indicated that CKD awareness in Nigeria is low. The social change implication is that the findings may be used to increase awareness of the CKD mortality and morbidity rate in Nigeria to facilitate the development and implementation of health policies that could lower the morbidity and mortality rate of CKD.

Introdução: O perfil de morbidade e mortalidade no Brasil passou por uma transição demográfica, com o aumento da prevalência de doenças crônicas na população em geral, tais como diabetes mellitus (DM) e hipertensão arterial (HA), e como consequência, a doença renal crônica (DRC). Na última década, a DRC tem sido apresentada como um grande desafio para a saúde pública no Brasil e no mundo. Objetivo: O objetivo deste estudo foi identificar os fatores envolvidos na progressão da doença renal dos pacientes atendidos no Ambulatório de Uremia do HCFMRP-USP. Material e métodos: Trata-se de um estudo epidemiológico, transversal e retrospectivo de prontuários de pacientes do Ambulatório de Uremia, no período entre 2002 e 2012. Os dados foram extraídos dos registros médicos para a análise quantitativa e qualitativa. Resultados: A análise mostrou que 53% dos indivíduos eram do sexo masculino, com idade média de 61,21 anos. A mortalidade foi maior entre os idosos, que também apresentaram menor tempo de seguimento ambulatorial. A doença de base principal foi a HA (42,94%) e o tempo médio de seguimento foi de 11,23 meses. O encaminhamento para hemodiálise (44,48%) foi o desfecho clínico mais comum. Os principais fatores relacionados à progressão da DRC foram baixos níveis séricos de albumina, baixo valor de depuração da creatinina, pressão arterial não controlada e níveis séricos elevados de colesterol total. Discussão: A DRC tem aumentada progressivamente na população, especialmente entre os idosos, onde a taxa de mortalidade é maior e eles têm menos tempo de acompanhamento. As causas mais comuns das doenças de base foram HA e DM e vários fatores estavam envolvidos na progressão da doença renal. Aqueles indivíduos que tiveram DM como doença de base evoluíram mais rápido do que os outros para diálise. Conclusão: Os níveis séricos baixos de albumina, baixo valor de depuração da creatinina, pressão arterial não controlada e níveis séricos elevados de colesterol total são fatores envolvidos na progressão da doença renal, e são fatores modificáveis que através de intervenções multidisciplinares durante o tratamento conservador pode retardar a progressão da DRC para diálise. / Introduction: The profile of morbidity and mortality in Brazil has undergone a demographic transition, with increasing prevalence of chronic diseases in the general population, such as diabetes mellitus (DM) and hypertension (H), and as a consequence the chronic kidney disease (CKD). In the last decade the CKD has been presented as a major challenge for public health in Brazil and worldwide. Objective: This study aims was to identify the factors involved in the progression of renal disease of patients attending in the Outpatient Uremia of the HCFMRP-USP. Material and methods: This is an epidemiological, cross-sectional and retrospective analysis of medical records of patients of Outpatient Uremia in the period between 2002 and 2012. The data were extracted of medical records for quantitative and qualitative analysis. Results: The analysis showed that 53% of subjects were male, with a mean age of 61.21 years. Mortality was higher among the elderly, who also presented shorter time of outpatient follow-up. The main underlying disease was H (42.94%) and the mean time of follow-up was 11.23 months. The referral for hemodialysis (44.48%) was the clinical outcome more common. The main factors related to the progression of CKD were low serum albumin, low value of creatinine clearance, high blood pressure levels and high serum levels of total cholesterol. Discussion: The CKD has been progressively increasing in the population, especially among the elderly, where the mortality rate is higher and they have less time of follow-up. The most common causes of underlying disease were H and DM and several factors were involved in the progression of kidney disease. Those individuals who had DM like underlying disease evolved faster than the others to dialysis. Conclusion: Low serum levels of albumin, low value of creatinine clearance, high blood pressure levels and high serum levels of total cholesterol are factors involved in the progression of renal disease, and are modifiable factors that through multidisciplinary interventions during conservative treatment can slow the progression of CKD to dialysis.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-05-06T17:58:43Z No. of bitstreams: 1 lucianadossantostirapani.pdf: 1416883 bytes, checksum: 1a79bea047bbedac18db6f9798555854 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-06-08T14:41:23Z (GMT) No. of bitstreams: 1 lucianadossantostirapani.pdf: 1416883 bytes, checksum: 1a79bea047bbedac18db6f9798555854 (MD5) / Made available in DSpace on 2016-06-08T14:41:23Z (GMT). No. of bitstreams: 1 lucianadossantostirapani.pdf: 1416883 bytes, checksum: 1a79bea047bbedac18db6f9798555854 (MD5) Previous issue date: 2013-08-02 / Introdução: O Serviço social entra oficialmente para o rol de profissões da saúde com a resolução do ministério da saúde nº 218/97. Esse reconhecimento da profissão perpassa um processo histórico, marcado pelas condições históricas nas quais a saúde pública se desenvolveu no Brasil e pelo reconhecimento social da profissão. Dentro da intervenção do Serviço Social na saúde, encontramos um novo campo de atuação que é o da nefrologia, uma atuação que, nos centros de Terapia Renal Substitutiva (TRS), possui um respaldo legal, sendo um reconhecimento da importância dos assistentes sociais na composição das equipes mínimas de atenção ao usuário com Doença Renal Crônica (DRC) em TRS. A associação entre fatores socioeconômicos e incidência e prevalência de DRC está bem determinada na literatura. Indubitavelmente, a etnia é o fator social mais estudado no que diz respeito à incidência e prevalência da DRC. Apenas recentemente, fatores educacionais têm sido abordados com relação à DRC, analisando a importância do autoconhecimento da patologia e a melhora dos desfechos. Um problema frequentemente abordado é a dificuldade de acesso aos serviços de saúde, tanto em países desenvolvidos, com modelos de sistemas de saúde que não são universais, como nos Estados Unidos, quanto em países em desenvolvimento, com populações com baixo nível socioeconômico, como o Brasil. Fatores como o gênero também tem sido abordados em poucos estudos, com mulheres tendo maior incidência de DRC. Quando avaliamos a influência desses mesmos fatores na progressão da DRC, há apenas escassos e fragmentados estudos que avaliam a questão, e vemos claramente que os estudos que avaliam a progressão da DRC abordam prioritariamente fatores biológicos. O objetivo deste estudo foi caracterizar o perfil social dos usuários com doença renal crônica pré-dialítica nos estágios 3, 4 e 5, como também avaliar o impacto das variáveis socioeconômicas na progressão da DRC pré-dialítica nos estágios estudados. Usuários e Métodos: Foi feito um estudo de coorte retrospectivo, período de acompanhamento de janeiro de 2002 a dezembro de 2009. As variáveis analisadas foram sociodemográficas, clínicas e laboratoriais. Os critérios de inclusão: usuários com mais de 18 anos de idade, DRC estágios 3A, 3B, 4 e 5, acompanhados por mais de três meses. Análise Estatística: Os usuários foram divididos de acordo com a vulnerabilidade social (VS). Para calcular a VS, foram utilizadas três técnicas estatísticas em seqüência, análise fatorial, análise de cluster (Cluster) e análise discriminante. Os dados sociodemográficos, clínicos e laboratoriais foram avaliados para cada grupo de VS. Foi realizada uma análise descritiva dos dados, expressos em média ± desvio padrão, mediana ou percentagem, de acordo com a característica da variável. Para avaliar a normalidade, utilizamos o teste de Kolmogorov-Smirnov. Diferenças entre os grupos foram analisadas pelo teste t para amostras independentes ou o teste de Wilcoxon para as comparações não-paramétricas. Um teste de χ2 foi usado para variáveis categóricas. A sobrevida foi analisada com curvas de sobrevida de Kaplan-Meier. O desfecho foi mortalidade ou iniciar a terapia renal substitutiva (TRS), analisadas por uma regressão de Cox. Resultados: Foram avaliados 209 usuários, acompanhados por um período de 7 anos, 29,4% foram classificados como vulneráveis. Não observamos diferença na mortalidade entre os usuários vulneráveis e não vulneráveis (log rank: 0,23), o que também ocorreu quando o resultado foi TRS (log rank: 0,17). No modelo de regressão de Cox, risco relativo (RR) e intervalo de confiança (IC) para o impacto da VS sobre a mortalidade, não ajustado foi RR: 1,87 (IC: 0,64-5,41) e, após RR ajustado: 1,47 (C1: 0,35-6,0). Quando analisamos o impacto da VS em TRS, observamos o R RR não ajustado: 1,85 (IC: 0,71-4,8) e RR ajustado: 2,19 (CI :0.50-9 0,6). Conclusão: A VS não apresentou impacto nos desfechos óbito e TRS. O acesso aos cuidados de saúde, no Brasil, apesar de suas características universais, tem barreiras sociais no acesso ao tratamento especializado. Acreditamos que os usuários passaram pelas barreiras sociais impostas para o 7 acesso a cuidados especializados (viés de seleção). Nosso estudo apresenta limitações, já que não nos permite comprovar a eficácia de uma intervenção interdisciplinar, uma vez que o desenho do estudo adotado (coorte retorspectiva) não nos permite avaliar o impacto da aborgadem interdisciplinar, pois a coleta dos dados ocorreu após a intervenção da equipe.No entanto, o presente estudo é o primeiro a avaliar a VS em usuários com DRC em pré-diálise, por um período de acompanhameto de sete anos. / Introduction: The Social Work officially enter the ranks of health professions with the resolution of the Ministry of Health No. 218/97. This recognition of the profession goes through a historical process marked by the historical conditions in which public health was developed in Brazil and the social recognition of profession. Inside Social Service Health, found a new playing field that is nephrology, a performance that, in the centers of Renal Replacement Therapy (RRT), has a legal backing, and a recognition of the importance of social workers in the composition teams minimal attention to patient with Chronic Kidney Disease (CKD) in TRS. The association between socioeconomic factors and incidence and prevalence of CKD is well established in the literature. Undoubtedly, the ethnicity is the most studied social factor with regard to the incidence and prevalence of CKD. Only recently, educational factors have been addressed with respect to CKD, analyzing the importance of self-pathology and improves outcomes. An issue often discussed is the difficulty of access to health services, both in developed countries, with models of health systems that are not universal, as in the United States and in developing countries with populations with low socioeconomic status, as Brazil. Factors such as the genre has also been addressed in a few studies, with women having higher incidence of CKD. When we evaluated the influence of these same factors in the progression of CKD, there is only scarce and fragmented studies evaluating the issue, and we see clearly that studies evaluating the progression of CKD deal primarily biological. The aim of this study was to characterize the social profile of users with chronic kidney disease pre-dialysis stages 3, 4 and 5, as well as assess the impact of socioeconomic variables on the progression of CKD pre-dialysis stages studied. Patients and Methods:: We conducted a retrospective cohort study, follow-up period from January 2002 to December 2009. The variables were sociodemographic, clinical and laboratory. Inclusion criteria: users over 18 years of age, CKD stages 3A, 3B, 4 and 5, accompanied by more than three months. Statistical Analysis: The users were divided according to social vulnerability (SV). To calculate the VS, we used three statistical techniques in sequence, factor analysis, cluster analysis (Cluster) and discriminant analysis. The demographic data, clinical and laboratory data were evaluated for each group of VS. We performed a descriptive analysis of the data, expressed as mean ± standard deviation, median, or percentage, according to the characteristic of the variable. To assess normality, we used the Kolmogorov-Smirnov test. Differences between groups were analyzed by t test for independent samples or the Wilcoxon test for nonparametric comparisons. A χ2 test was used for categorical variables. Survival was analyzed with survival curves of Kaplan-Meier. Cox regression was performed to examine the impact of SV on the outcomes. Results. We evaluated 209 patients cared for a period of 7 years, 29.4% were classified as vulnerable. There were no differences in mortality among the vulnerable and non-vulnerable users (log rank: 0.23), which also occurred when the result was TRS (log rank: 0,17). In the Cox regression model, hazard ratio (HR) and confidence interval (CI) for the impact of VS on mortality was not adjusted HR: 1.87 (CI: 0.64 to 5.41) and after adjusted HR: 1.47 (C1: 0.35 to 6.0). When we analyze the impact of VS on TRS, observe the HR and CI, unadjusted HR: 1.85 (CI: 0.71 to 4.8) and adjusted HR: 2.19 (CI:0.50-9 0.6) . Conclusion: VS showed no impact on mortality outcomes and TRS. Access to health care in Brazil, despite its universal features, have social barriers in access to specialized treatment. We believe that users spent by social barriers imposed for access to specialized care (selection bias). Our study has limitations, as it does not allow us to prove the effectiveness of an interdisciplinary intervention, since the method adopted (retrospective cohort) did not allow us to evaluate the impact of an interdisciplinary approach, because data collection occurred 9 after the intervention team. However, the present study is the first to evaluate the VS in users with CKD pre-dialysis, for a follow-up period of seven years.

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.

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.

Thesis (PhD)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Despite the high prevalence of chronic kidney disease, renal narratives are under-reported. Much of what is written on kidney failure is written by health care professionals for health care professionals and about patients. While medical experts and health care practitioners have one type of knowledge, their patients have another type of knowledge acquired through their experience of their own condition. From within the disability and patients’ rights movements urgent calls have been made for the authentic voices of disabled people and patients to be heard without the mediation of professional lenses. In response to this my dissertation combines personal and academic writing to explore my own experience of end-stage renal disease, dialysis, transplantation and the life after transplant. I have used autoethnography as a methodology. Autoethnography is a relatively new, somewhat postmodern form of inquiry that developed from the reflexive turn in anthropology and narrative studies in the latter part of the twentieth century. It is very useful in writing about the experience of illness and reflecting on illness narratives because, in autoethnographic writing, the observer and observed, the narrator and narrated, insider and outsider are the same person. This allows scope for exploring the problematics of representation and for finding alternatives to already existing ways of telling certain stories. Engaging with autoethnography’s postmodern aspects has allowed me to conceptualize experiences that, until I undertook this research, I have never been able to articulate, because the traditional (static) illness narrative forms did not speak to my experience or my understanding of my condition. The central issue in my dissertation lies in the question: How do I tell the story of chronic illness once I have had an organ transplant? Flowing from this are a number of sub-issues: Can my story change? How do I describe myself: The well, the ill, the impaired, the disabled, the afflicted? Do I describe myself living in no man’s land? In my narrative, do I oscillate between being well and ill, or do I occupy another territory entirely? And if I do, what is it? My study shows that writing the story (or stories) of chronic kidney disease is complex, nuanced and dynamic and that, far from being an extended liminal experience, kidney disease is littoral. This distinction is important in coming to narrative terms with an identity that is not damaged so much as different. Through this I hope to demonstrate to both outsiders and insiders, who often submit to narratives that are forced on them, that more satisfying alternatives can be found. / AFRIKAANSE OPSOMMING: Ondanks die hoë voorkomssyfer van chroniese nierkwale word nierverhale nie genoeg aangemeld nie. Die meerderheid van dit wat oor nierversaking geskryf word, word deur gesondheidsorgdeskundiges vir gesondheidsorgdeskundiges en oor pasiënte geskryf. Terwyl mediese deskundiges en gesondheidsorgpraktisyns een soort kennis het, het hulle pasiënte ’n ander soort kennis op grond van hulle ervaring van hulle eie toestande. Van binne die gestremdheid en pasiënteregte-bewegings het ’n dringende oproep weerklink vir die outentieke stemme van mense met gestremdhede en pasiënte om gehoor te word sonder die tussenkoms van professionele perspektiewe. In reaksie hierop kombineer my verhandeling persoonlike en akademiese beskrywings om my eie ervaring van eindstadium- nierkwale, dialise, oorplanting en die lewe na oorplanting te verken. Ek het outo-etnografie as metodologie gebruik. Outo-etnografie is ’n relatief nuwe, ietwat postmoderne vorm van ondersoek wat in die tweede deel van die twintigste eeu uit die refleksiewe wending in antropologie en narratiewe studies ontwikkel het. Dit is baie bruikbaar wanneer oor die belewenis van siekte en besinning oor siekte-narratiewe geskryf word aangesien die waarnemer en die waargeneemde, die verteller en dit wat vertel word, die ingewyde en die buitestander in outo-etnografiese skryfwerk dieselfde persoon is. Dit laat meer ruimte vir verkenning van die problematiek van voorstelling en vir die opspoor van alternatiewe vir reeds bestaande wyses om sekere stories te vertel. My bemoeienis met postmoderne aspekte van outo-etnografie het dit vir my moontlik gemaak om ervaringe wat ek tot en met hierdie navorsing nooit kon artikuleer nie, te konseptualiseer, aangesien die tradisionele (statiese) vorme van siekte-narratiewe nie tot my ervaring of my begrip van my toestand gespreek het nie. ‘Hoe vertel ek die storie van chroniese siekte nadat ek ’n orgaanoorplanting gehad het?’ is ’n sentrale vraagstuk in my verhandeling. Hieruit spruit ’n aantal newevraagstukke voort: Kan my storie verander? Hoe beskryf ek myself: Die gesonde persoon, die sieke, die verswakte, die gestremde, die aangetaste? Hoe beskryf ek myself wat in ’n niemandsland woon? Fluktueer ek in my narratief tussen gesond wees en siek wees of betrek ek ’n geheel ander gebied? En indien wel, wat is dit? My studie toon dat, om die storie (of stories) van chroniese niersiekte te skryf, kompleks, genuanseerd en dinamies is en dat niersiekte glad nie ’n uitgebreide liminale ervaring is nie, maar eerder littoraal is. Dit is belangrik wanneer daar tot ’n narratiewe verstandhouding gekom moet word met ’n identiteit wat nie soseer beskadig is nie, maar eerder anders. Hierdeur hoop ek om aan beide buitestanders en ingewydes, wat dikwels voor narratiewe wat op hulle afgedwing word, moet buig, te wys dat daar meer bevredigende alternatiewe gekry kan word.

In 2008, El Salvador registered the world's highest mortality rate from kidney failure, with more than 2500 deaths annually in Central America's smallest country. El Salvador is the ground zero of a new form of Chronic Kidney Disease (CKD) that has become an epidemic among otherwise healthy agricultural workers and rural residents in lowland Central America in the past three decades. While the epidemic is believed to stem from some combination of agro- chemical exposure and/or dehydration, research on the disease remains embroiled in controversy, policy changes few, and medical support for affected individuals challenging. Foucaultian theorizations of 'discursive materiality' provide insights into the ways in which–even as the science remains inconclusive–understandings, discussions, and research on CKD in El Salvador are having material effects on individuals' bodies and health statuses. Based on fieldwork in El Salvador in summer 2014, this thesis uses the lens of Salvadorian CKD to explore the workings of biopower in settings of industrial agricultural production. Focusing on the Bajo Lempa region of El Salvador, in particular, the thesis examines the discourses, materialities, and practices through which CKD has "come to matter" as a medical and political phenomenon in relation to the agriculture through which affected Salvadorians make their living. Thinking through the discursive materialities of CKD alongside the production of spaces of health and agriculture, this thesis provides insights for the growing field of the political ecology of health by investigating the wider socio-political and environmental processes that make CKD management such a challenge in a Central America.

Renal replacement therapy, in the form of dialysis or transplantation, is the cornerstone of management for end-stage renal disease. UK renal registry shows nearly half of those needing renal replacement therapy are treated by dialysis – predominantly by haemodialysis. Patients on renal replacement therapy have increased mortality risk compared to age matched general population. Moreover, some specific subgroups of patients on haemodialysis have increased risk of mortality than expected. The survival benefit seen in women in the general population is attenuated resulting in similar survival for men and women on haemodialysis therapy. In addition, obese individuals and those of non-Caucasian origin have better survival outcome. Though the underlying reason for these findings is not clear and is likely to be multi-factorial, it has been hypothesised that this paradox could be due to the current practice of normalising dialysis dose to total body water. A number of metabolic factors – body surface area, resting energy expenditure and total energy expenditure – have been proposed as alternative to total body water for scaling dialysis dose. There were two overarching aims of this work – one was to study the effect of declining renal function on resting and total energy expenditure and to study the influence of various energy expenditure measures on uraemic toxin generation. The second was to study the impact on survival outcome of using these alternate parameters for normalising dialysis dose and to derive dialysis dose adjustments based on these metabolic parameters. In order to study these aims, studies were designed to explore different aspects of energy expenditure measures along with a longitudinal study to examine the impact of these parameters on survival outcome. The relationship between energy metabolism, body composition and uraemic toxin generation was studied with a retrospective analysis of 166 haemodialysis patients in whom urea generation rate was used as surrogate marker of uraemic toxin generation. It was found that total energy expenditure and fat-free mass predicted uraemic toxin generation after adjustment for other relevant variables. This study provided the preliminary data which was useful in designing further studies for this work. The effect of renal function on resting and total energy expenditure was studied in 80 patients with varying stages of chronic kidney disease who were not on renal replacement therapy. Resting and total energy expenditures were measured directly using gold-standard methods. It was found that declining renal function did not have a significant influence on either of these measures. This supports the hypothesis that metabolic rate is the driving force for glomerular filtration rate and not vice-versa. The directly measured energy expenditure measures were also found to have a moderately strong relationship with urea generation rate in these patients not on renal replacement therapy. The impact of physical activity on uraemic toxin generation, and thereby dialysis requirement, was studied in a prospective cross-sectional study of 120 haemodialysis patients in whom the physical activity was measured by an accelerometer device. Results from the study showed physical activity level to be a significant predictor of uraemic toxin generation after adjustment for gender and body size differences. This study results stressed the importance of adjusting dialysis dose based on individual’s physical activity level. To study the impact of using metabolic factors as normalising parameter for scaling dialysis dose on survival outcome, a large-scale longitudinal study was conducted with 1500 maintenance haemodialysis patients recruited for the study. Dialysis dose-related parameters and survival outcomes were collected at baseline and at various time points during the follow-up period of 18 months. Study results were analysed in two parts - the theoretical basis for using these metabolic factors as scaling parameters was explored which showed that current minimum target dialysis dose risks under-dialysis in certain subgroups of patients and using these alternative parameters may provide a more equivalent dialysis dose across individuals of different body sizes and gender. With these results arguing for potential use of the alternative parameters, the impact on survival of using them were examined. It was found that all three parameters performed better than the current parameter (total body water) with regards to predicting mortality. Total energy expenditure was found to be the best parameter with the lowest hazard ratio for risk of death. The study data was also analysed to derive an algorithm for adjustment of minimum target dialysis dose based on body size and physical activity level. This newly derived minimum dose target was also shown to impact on survival with those underdialysed based on this criteria having poorer survival outcomes. To understand the impact of whole body protein turnover on resting energy expenditure and uraemic toxin generation, a cross-sectional study was conducted on 12 patients with advanced CKD – 6 each in pre-dialysis CKD and haemodialysis group. It was found that haemodialysis patients had higher rate of protein turnover compared to pre-dialysis patients. Whole body protein turnover was found to contribute significantly to resting energy expenditure and had a moderately strong relationship with urea generation rate. In the course of these studies, two questionnaire tools have been validated for use for clinical and research purposes – one is a self-report comorbidity questionnaire and the other, the Recent Physical Activity Questionnaire. The comorbidity questionnaire was developed as part of this work and was validated against Charlson Comorbidity Index. The Recent Physical Activity Questionnaire was validated for physical activity data collection and energy expenditure calculation against the gold-standard doubly labelled water method. In conclusion, it has been demonstrated that metabolic factors such as body surface area, resting energy expenditure and total energy expenditure are more closely related to uraemic toxin generation compared to total body water. It has also been demonstrated that physical activity contributes to metabolic waste production and may necessitate changes in dialysis requirement. It has been shown that these metabolic factors, when used as scaling parameter for dialysis dosing, may predict survival better than the current parameter in use. The algorithm for dialysis dose adjustment and the questionnaires validated in this work have provided novel tools for further research studies and clinical practice. The central hypothesis of this work is that some metabolic factors may be better markers of uraemic toxin generation compared to total body water. It is hypothesised that modifications in dialysis practice based on these factors may improve the quality of haemodialysis and favourably impact on survival outcome for patients with end-stage renal disease. The work presented here largely supports this hypothesis.