京都大学 / 新制・課程博士 / 博士(医学) / 甲第25005号 / 医博第5039号 / 新制||医||1070(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 羽賀 博典, 教授 竹内 理, 教授 小林 恭 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Patients with chronic kidney disease are at increased risk of cardiovascular disease. These patients are often excluded in randomized controlled trials of treatments for cardiovascular disease, leading to greater uncertainty behind treatment effects in this population. Further, patients with kidney disease experience unique complications from accepted therapies for the general population, e.g.; long-term anticoagulation may be result in further kidney injury called anticoagulation-related nephropathy. However, incidence and magnitude of this acute kidney injury are not adequately measured in past randomized controlled trials of anticoagulation. Chapters in this thesis aim to increase our understanding the relationship between cardiac and kidney disease. Chapters 2 and 3 focus on the optimal prosthetic valve in dialysis patients requiring valve replacement surgery. Chapter 2 is a systematic review and meta-analysis comparing the short and long-term outcomes of two prosthetic valves implanted in dialysis patients. Chapter 3 is a survey of physicians aiming to understand the current practice of nephrologists, cardiologists, and cardiac surgeons caring for dialysis patients requiring valve replacement surgery and their preference for either prosthetic valve based on patient factors. Chapter 4 explores the interaction between an individual’s baseline kidney function and the effect on stroke reduction of occluding the left atrial appendage. This is accomplished by a secondary analysis of the Left Atrial Appendage Occlusion Study 3 (LAAOS III). Chapter 5 is a rationale and study design of LIMIT-Renal, a substudy of Low INR to Minimize Bleeding with Mechanical Valves Trial (LIMIT). This substudy aims to validate the existence of anticoagulation-related nephropathy, a form of acute kidney injury in patients receiving long-term anticoagulation, and its magnitude on renal health. Chapter 6 is the conclusion of the thesis and discusses key findings, strengths and limitations, future directions, and potential obstacles. / Thesis / Doctor of Science (PhD) / Individuals with chronic kidney disease are at an increased risk of heart disease and those receiving treatment for heart disease may be at an increased risk of developing kidney disease. Chapters in this thesis investigate the understudied interplay of heart disease and renal disease, for which an overview is presented in chapter 1. Chapter 2 addresses the uncertainty surrounding an optimal prosthetic valve in dialysis patients requiring surgical valve replacement surgery. Chapter 3 aims to understand the perceptions and preferences of physicians caring for dialysis patients needing valve replacement surgery. Chapter 4 explores the interaction between occluding the left atrial appendage and baseline kidney function on stroke reduction using data from the Left Atrial Appendage Occlusion Study 3 (LAAOS III). Chapter 5 is the design and rationale for a substudy of Low INR to Minimize Bleeding with Mechanical Valves Trial (LIMIT) exploring a form of acute kidney injury in patients receiving blood-thinning medications. Chapter 6 discusses the key findings from each chapter, their strengths and limitations, future directions, and potential obstacles.

INTRODUÇÃO: A avaliação da QV tem se destacado de modo crescente em pesquisas clínicas de pacientes com insuficiência renal crônica terminal (IRCT), sendo o SF-36 um dos instrumentos mais utilizados nesta população. O objetivo deste estudo foi avaliar e comparar a QV nos pacientes com IRCT que estavam em tratamento dialítico de DPA e HD utilizando o SF-36 e avaliar se parâmetros sociais, demográficos, econômicos, clínicos e de adequação em diálise interferem na QV desses grupos. MÉTODOS: este estudo transversal, prospectivo e observacional, foi realizado em uma unidade de diálise satélite no município de São Paulo, em dezembro de 2003. Foram incluídos no estudo os pacientes de DPA ou HD, com tempo na terapia maior que 90 dias, idade entre 18 e 75 anos, com domínio da língua portuguesa e que concordaram em responder o instrumento para avaliação da QV. Participaram 22 pacientes de DPA e 79 de HD. Através do prontuário médico, foram coletados dados demográficos, sociais, econômicos, informações clínicas e exames laboratoriais. A QV foi avaliada apenas uma vez durante entrevista com a pesquisadora. Os valores obtidos na QV foram cruzados com as demais variáveis para verificar se havia interação significativa. RESULTADOS: Os grupos foram muito semelhantes entre si na maioria das variáveis analisadas. Na HD observou-se tempo maior de tratamento (p=0.002) e níveis de albumina sérica mais elevados que DPA (p<0,001). Em DPA, mais pacientes possuíam seguro saúde privado (p=0,018). A avaliação da QV é semelhante em quase todos os domínios do SF-36, a única diferença significativa ocorreu no Aspecto Físico, onde HD teve um escore maior que DPA (p=0,007). Não ocorreu nenhuma interação significativa entre este domínio e as demais variáveis analisadas que justificasse a diferença encontrada. CONCLUSÃO: A QV foi muito semelhante entre as duas modalidades de diálise. O grupo de HD apresentou melhor resultado em relação ao Aspecto Físico, sendo que este fato parece depender unicamente do método dialítico / The evaluation of health-related Quality of Life (Qol) is fundamental when searching for better treatment in end-stage renal disease (ESRD). The SF-36 is the most used questionnaire for this population. The purpose of this study was evaluated and compared the Qol in ESRD patients during either automatic peritoneal dialysis (APD) or hemodialysis (HD) treatment using the SF-36. METHODS: this is a prospective, cross-sectional and observational study, performed in a single dialysis facility in the city of São Paulo. Patients, with an age between 18 and 75 years, should be for more than 90 days in therapy and besides showing fluency in Portuguese language should be able to understand the questionnaire. Twenty-two APD and 79 HD patients were enrolled. The social, demographics, economics, clinical and laboratories information were colleted from the electronic data base. The Qol was assessed once an interview with one of the authors. The scores of SF-36 was correlated with the others variables to verify possible interactions. RESULTS: Both groups were very similar in most of the analyzed variables. Time in therapy was longer (p=0.002) and serum albumin level was higher (p<0,001) for the HD group than APD. In APD group more patients had private health insurance (p=0,018). The scores of SF-36 were similar in the various dimensions of the Qol questionnaire. The mean score for Physical Functioning was higher in HD than in APD (p=0,007). No significant interactions between the SF-36 dimensions and the others variables explained this difference. CONCLUSION: The Qol was very similar between these two dialysis modalities. The HD group showed better scores in Physical Functioning and this seemed to depend on the type of dialysis modality only

Background and aim: There had been no randomized end-point studies with statins for patients with severe renal failure. The purpose of this prospective, open, randomized, controlled study was to investigate whether atorvastatin (10 mg/day) would alter cardiovascular end-points and the overall mortality rate of patients with chronic kidney disease stage 4 or 5 (creatinine clearance&lt;/30 ml/min) and to influence risk factors. Material &amp; Methods: This was an open, prospective, randomized study. A total of 143 patients were included: 73 were controls and 70 were prescribed 10 mg/day of atorvastatin. As efficacy variables, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride levels were determined at the start of the study and at 1, 3, 6, 12, 18, 24, 30 and 36 months. The primary end-points were all cause of mortality, non-lethal acute myocardial infarction, and coronary artery intervention. Various risk factors were studied. In the 97 patients on haemodialysis inter dialysis weight gain (IDWG) was calculated as ultrafiltration in kg/body weight in kg given in percentage of the weight. The burden of IDWG was analyzed. Results: In the atorvastatin group, total cholesterol and low-density lipoprotein cholesterol were significantly reduced, the latter by 35% at 1 month and then sustained. Atorvastatin was withdrawn in 23% of patients due to unacceptable side effects, most frequent complaints being gastrointestinal discomfort and headache. Primary end-points occurred in 74% of the subjects. There was no difference in cardiovascular endpoint and survival between the control and atorvastatin groups. The 5-year end-point-free survival rate from study entry was 20%. There was no evidence of more benefit of atorvastatin for patients with diabetes mellitus and chronic kidney disease versus the other patients; instead plasma fibrinogen increased. The IDWG was significantly larger in patients who suffered from end-points due to cardiovascular reasons, cardiac reasons, congestive heart failure, aortic aneurysm, and intracerebral bleeding. Conclusion: These data showed that in contrast to other patient groups, patients with severe chronic kidney disease 4 and 5, including those with diabetes mellitus, seem to have no benefit from 10mg/day of atorvastatin. Instead we found a high IDWG to be an important risk factor that should be prevented. There was no evident connection between atorvastatin medication and IDWG.

Introduction: Forty years ago the life saving and life prolonging therapy of dialysis was rationed. It was extremely unlikely that people aged over 50 years would be offered treatment. Today, those aged over 65 years are becoming the fastest growing group of patients on dialysis. Changing population demographics and referral patterns, the opening up of eligibility for dialysis to high risk individuals, refinement and developments in dialysis technology and its ‘success’ in keeping more patients alive for longer periods, along with rising public expectation, are just some of the reasons behind this change in the age profile of those being currently treated for kidney failure. Older people are likely to have multiple co-morbidities and decreased functional status that may complicate their decision-making about dialysis and limit their treatment options. / Enhancing choice and involvement in treatment decision-making to the patient’s satisfaction is a central theme of health care ethics. Current national and international ethical guidelines about the initiation of dialysis recommend shared or joint decision-making and discuss patient ‘benefit’ and patient ‘need’. This project sought to determine how these recommendations, and other ethical issues related to informed consent, possible withdrawal of treatment and quality of life, were embodied in the personal experiences of a group of older people facing dialysis decisions. / Aim: The general aim of this research was to follow the dialysis decision-making process over time amongst a group of people aged 65 years and older. More specifically, this research sought to explore with the participants the following issues: what factors impacted on their dialysis decision-making; how they understood both what was happening to them and the goals of treatment; their preferences for information seeking; how they perceived any future decision-making; how or whether the commencement and experience of dialysis influenced their decision-making; and once treatment had been initiated, how they felt about their initial decisions. / Method: A predominantly longitudinal qualitative study was undertaken. Meetings were conducted prior to the potential initiation of dialysis with 21 participants. These meetings involved a semi-structured interview and the administration of three questionnaires focusing on preferences for decision-making, information seeking and quality of life. Data was also collected from the participants’ health records. For those participants who commenced dialysis a further two meetings were undertaken one month and then six months after treatment was instigated. The qualitative data was analysed thematically using concepts that had either been pre-determined and explored within the interviews or, had emerged from the participants’ stories. / Findings: Findings from this study include: participants not feeling that they had a choice about dialysis; a mismatch between theoretical expectations of informed consent and shared decision-making and the ‘actor centred experiential’ model of decision-making adopted by participants; a need to re-evaluate the balance and relationships between physiological measures of effectiveness emphasised by health professionals, and psychosocial and functional markers valued by participants; and treatment goals not being individually negotiated. / Conclusion: An interest in remaining alive was the driving force behind why participants chose to have dialysis. Other factors impacting on decisions about dialysis were multi-faceted and were based on priorities other than what health professionals consider important. Shared decision-making, as described in the literature, is not unproblematic. However, health professionals need to accept the underlying premises on which shared decision-making is based so that they can find out what expectations patients have of treatment, beyond that of saving life. Such expectations need to be discussed with patients and the various treatment options need to be negotiated in an attempt to achieve patients’ goals. Patients should be encouraged however to be involved in decision-making to the extent to which they desire.

Orientador: Daniela Ponce / Resumo: Introdução: Poucos trabalhos avaliaram a viabilidade e os resultados entre diálise peritoneal (DP) e hemodiálise (HD) no início urgente de terapia renal substitutiva (TRS). Objetivo: Comparar DP e HD como opções de início urgente de TRS, quanto à evolução, desfechos e complicações dos pacientes. Método: Estudo quasi experimental com pacientes incidentes em DP e HD em hospital universitário brasileiro, no período de julho/2014 a dezembro/2016. Incluídos indivíduos DRC estádio final que necessitaram de TRS imediata, ou seja, HD por meio de CVC ou DP cujo cateter foi implantado por nefrologista e utilizado em 72 horas, sem treinamento prévio. Pacientes em DP foram submetidos, inicialmente, a DP de alto volume (DPAV) para compensação metabólica. Após alta hospitalar, permaneciam em DP intermitente na unidade de diálise até efetivação do treinamento. Foram comparados: complicações mecânicas e infecciosas, recuperação de função renal e sobrevida. Resultados: Foram incluídos 93 pacientes em DP (G1) e 91, em HD (G2). Os grupos G1 e G2 foram semelhantes quanto à idade (58+17 vs 60+15; p=0,49), frequência de diabetes mellitus (37,6 vs 50,5%; p=0,10), outras comorbidades (74,1 vs 71,4%; p=0,67) e parâmetros bioquímicos ao início da TRS – creatinina (9,1+4,1 vs 8,0+2,8; p=0,09), albumina sérica (3,1+0,6 vs 3,3+0,6; p=0,06) e hemoglobina (9,5+1,8 vs 9,8+2,0; p=0,44). Após seguimento mínimo de 180 dias e máximo de dois anos, não houve diferença quanto a complicações mecânicas (24,7 vs 37,4... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Few studies have evaluated the feasibility and results of peritoneal dialysis (PD) and hemodialysis (HD) at the urgent-start of renal replacement therapy (RRT). Objective: We compared PD and HD as options for urgent-start of RRT regarding the evolution, complications and outcomes of patients. Method: End-stage renal disease (ESRD) patients who initiated dialysis urgently without a pre-established functional vascular acess or PD catheter were included in a period between July/2014 to December/2016, from a Brazilian single centre. In urgent-start PD, nephrologists performed the Tenckhoff catheter insertions. It was used high volume PD (HVPD) right after 72 hours PD catheter placement, and it was kept until metabolic and fluid control. After hospital discharge, patients were treated with intermittent PD on alternate days at the dialysis unit, until family training. Results: Ninety-three patients in PD (G1) and 91 in HD (G2) were included. Comparing the G1 group with G2, they were similar in age (58±17 vs 60±15; p= 0.49), frequency of diabetes mellitus (37.6 vs 50.5%; p= 0.10), others comorbidities (74.1 vs 71.4%; p= 0.67) and biochemical parameters to early RRT - creatinine (9.1+4.1 vs 8.0+2.8; p= 0.09), serum albumin (3.1+0.6 vs 3.3+0.6; p= 0.06) and hemoglobin (9.5+1.8 vs 9.8+2.0; p= 0.44). There was no difference between the groups in mechanical complications (24.7 vs 37.4%; p= 0.06) and bacteremia (15 vs 24%; p= 0.11). Exit site infection (ESI) (25.8 vs 39.5%; p ... (Complete abstract click electronic access below) / Doutor

INTRODUÇÃO: A avaliação da QV tem se destacado de modo crescente em pesquisas clínicas de pacientes com insuficiência renal crônica terminal (IRCT), sendo o SF-36 um dos instrumentos mais utilizados nesta população. O objetivo deste estudo foi avaliar e comparar a QV nos pacientes com IRCT que estavam em tratamento dialítico de DPA e HD utilizando o SF-36 e avaliar se parâmetros sociais, demográficos, econômicos, clínicos e de adequação em diálise interferem na QV desses grupos. MÉTODOS: este estudo transversal, prospectivo e observacional, foi realizado em uma unidade de diálise satélite no município de São Paulo, em dezembro de 2003. Foram incluídos no estudo os pacientes de DPA ou HD, com tempo na terapia maior que 90 dias, idade entre 18 e 75 anos, com domínio da língua portuguesa e que concordaram em responder o instrumento para avaliação da QV. Participaram 22 pacientes de DPA e 79 de HD. Através do prontuário médico, foram coletados dados demográficos, sociais, econômicos, informações clínicas e exames laboratoriais. A QV foi avaliada apenas uma vez durante entrevista com a pesquisadora. Os valores obtidos na QV foram cruzados com as demais variáveis para verificar se havia interação significativa. RESULTADOS: Os grupos foram muito semelhantes entre si na maioria das variáveis analisadas. Na HD observou-se tempo maior de tratamento (p=0.002) e níveis de albumina sérica mais elevados que DPA (p<0,001). Em DPA, mais pacientes possuíam seguro saúde privado (p=0,018). A avaliação da QV é semelhante em quase todos os domínios do SF-36, a única diferença significativa ocorreu no Aspecto Físico, onde HD teve um escore maior que DPA (p=0,007). Não ocorreu nenhuma interação significativa entre este domínio e as demais variáveis analisadas que justificasse a diferença encontrada. CONCLUSÃO: A QV foi muito semelhante entre as duas modalidades de diálise. O grupo de HD apresentou melhor resultado em relação ao Aspecto Físico, sendo que este fato parece depender unicamente do método dialítico / The evaluation of health-related Quality of Life (Qol) is fundamental when searching for better treatment in end-stage renal disease (ESRD). The SF-36 is the most used questionnaire for this population. The purpose of this study was evaluated and compared the Qol in ESRD patients during either automatic peritoneal dialysis (APD) or hemodialysis (HD) treatment using the SF-36. METHODS: this is a prospective, cross-sectional and observational study, performed in a single dialysis facility in the city of São Paulo. Patients, with an age between 18 and 75 years, should be for more than 90 days in therapy and besides showing fluency in Portuguese language should be able to understand the questionnaire. Twenty-two APD and 79 HD patients were enrolled. The social, demographics, economics, clinical and laboratories information were colleted from the electronic data base. The Qol was assessed once an interview with one of the authors. The scores of SF-36 was correlated with the others variables to verify possible interactions. RESULTS: Both groups were very similar in most of the analyzed variables. Time in therapy was longer (p=0.002) and serum albumin level was higher (p<0,001) for the HD group than APD. In APD group more patients had private health insurance (p=0,018). The scores of SF-36 were similar in the various dimensions of the Qol questionnaire. The mean score for Physical Functioning was higher in HD than in APD (p=0,007). No significant interactions between the SF-36 dimensions and the others variables explained this difference. CONCLUSION: The Qol was very similar between these two dialysis modalities. The HD group showed better scores in Physical Functioning and this seemed to depend on the type of dialysis modality only

Thesis (M.Sc. (Statistics)) -- University of Limpopo, 2020 / Peritoneal Dialysis (PD) is a process of replacing kidney function which cleans waste from the blood and remove extra fluid from the body. In most cases, the process of PD is slowed down by a peritoneal membrane infection called peritonitis. Despite recent advancements in treatments and prevention, peritonitis still remains the leading complication which results in high morbidity and technique failure among PD patients. Using a prospective peritonitis dataset of 159 kidney patients who were on PD from 2008 to 2015 in Pietersburg Provincial Hospital, the aim of this study was to identify potential social, demographic and biological risk factors that contribute to the first episode of peritonitis. Both semi-parametric (Cox PH) and parametric (Accelerated Failure Time: Weibull, exponential, loglogistic, and gamma) survival models were fitted to the peritonitis dataset. Akaike Information Criterion (AIC) was applied to select models which best fit to the peritonitis data. Accordingly, log-logistic Accelerated Failure Time (AFT) model was found to be a working model that best fit to the data. A total of 96 (60.38%) peritonitis cases were recorded over the follow-up period with majority of peritonitis infection coming from females (65.4%) and rural dwellers (65.7%) with (62.6%) of black Africans showing higher risk of developing peritonitis. The multivariate log-logistic AFT model revealed that availability of water (p-value=0.018), electricity (p-value=0.018), dwelling (p-value=0.008), haemoglobin status (p-value=0.002) and duration on PD (p-value=0.001) are significant risk factors for the development of peritonitis. Therefore, patients with no water and electricity, coming from rural background with low level of haemoglobin and shorter duration on PD are associii ated with high risk or hazard of developing peritonitis for the first time.

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<p>This thesis consists of three related studies presented as three separate manuscripts. The first two comprise part of a larger sequential mixed-methods study with a qualitative and subsequent quantitative (survey) component. The overarching goal of this study was to understand the factors that influence the use of home dialysis, from the perspectives of Canadian nephrologists. The third study was a methodological study (a clinical trial) embedded in the survey, evaluating a novel strategy to incentivize survey responses.</p> <p>In the first paper, we aimed to develop a theoretical framework describing determinants of dialysis modality choice. We selected informants using a maximum-variation sampling strategy, and used in-depth interviews to explore their perspectives. We used a grounded theory-informed analytical approach to construct a taxonomy of barriers and related facilitators to home dialysis use. We triangulated our findings against related published studies and qualitative results from our survey study. This study informed the development of the questionnaire that is the focus of the second study.</p> <p>The second paper describes the development, administration, and results of a 47-item survey measuring Canadian nephrologist perspectives on the relevance of barriers to home dialysis use, and the utility of candidate interventions to overcome them. We used factor analysis to aggregate items into domains, and examined the relationships between respondent and practice characteristics with domain-level scores. Respondents expressed enthusiasm and reluctance towards a number of strategies to optimize home dialysis use. Our findings will guide policy development and further research directed at managing barriers to home dialysis use.</p> <p>The third and final study tests the effectiveness of a promised donation as an incentive for survey completion. We randomized survey recipients to receive standard notifications versus notifications that offered a charitable donation of $40 CAD to the Kidney Foundation of Canada in exchange for returning a completed survey. Contrary to our hypothesis, the intervention was not effective, thus adding to the cumulative evidence that such incentives do not impact on physician response rates.</p> / Master of Science (MSc)