Tesi sul tema "Peritoneal dialysis"

Individuals with end-stage kidney disease have the treatment options of receiving conservative care, dialysis or a kidney transplant. There are two main types of dialysis – haemodialysis and peritoneal dialysis. For a peritoneal dialysis (PD) program to be successful, close attention must be paid to preventing PD-related infections. A common and serious complication of PD is peritonitis. Peritonitis is a contributing cause of death in about 16% of PD patients and is a major cause of PD technique failure, which results in patients having to switch to long-term haemodialysis. The peritonitis rates of different renal centres are known to vary widely both within and between countries. Explanations for this variation are likely related to patient selection, patient training and infection-prevention protocols. This is a thesis by publication containing published and submitted work related to identifying barriers in practice to the uptake of relevant guideline recommendations, identifying current antimicrobial prophylaxis practice patterns in Australian and New Zealand (ANZ) PD units, assessing the evidence base for the antimicrobial agents used to prevent PD-related infections, and exploring patient experiences and beliefs about peritonitis. Chapter one is a general introduction to the topic. Chapter two is a narrative review of the literature relating to the prevention of PD-related infections. Chapter three is an original baseline study which assesses current practice and barriers to antimicrobial prophylaxis at 8 PD units. Chapter four is a systematic review of trials which have used various antimicrobial agents to prevent peritonitis in PD patients. Chapter five is an original survey study which assesses current antimicrobial prophylaxis practice at ANZ PD units. Chapter six is an original qualitative study that explores patients’ needs, experiences and beliefs about the prevention and treatment of peritonitis. The main aim of this thesis was to assess the current evidence base for the antimicrobial agents used, to establish current antimicrobial prophylaxis practice in ANZ PD units, to identify barriers to the uptake of guideline recommendations, and to explore patient experiences and beliefs about peritonitis and use the findings to suggest ways to improve the care and support they receive.

Worldwide, approximately 11% of patients on dialysis receive peritoneal dialysis (PD). Whilst PD may offer more autonomy to patients compared with hemodialysis, patient and caregiver burnout, technique failure, and peritonitis remain major challenges to the success of PD. Improvements in care and outcomes are likely to be mediated by randomised trials of innovative therapies, but will be limited if the outcomes measured and reported are not important for patients and clinicians. The aim of the Standardised Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) study is to establish a set of core outcomes for trials in patients receiving PD based on the shared priorities of all stakeholders, so that outcomes of most relevance for decision-making can be evaluated, and that interventions can be compared reliably. The phases of the SONG-PD project included in this thesis are: a systematic review to identify outcomes and outcome measures that have been reported in randomised trials involving patients receiving PD; focus groups using nominal group technique with patients and caregivers to identify, rank and describe reasons for their choice of outcomes; a 3-round international Delphi survey involving a multi-stakeholder panel; and a consensus workshop to review and endorse the proposed set of core outcome domains for PD trials. The establishment of 3 to 5 high-priority core outcomes, to be measured and reported consistently in all trials in PD, will enable patients and clinicians to make informed decisions about treatment based on outcomes of common importance.

A peritoneal dialysis cycler model was developed to be used by biomedical device manufacturers in order to aid them in the system development, system level requirement writing, and FDA device certification process. This generic model can be used as a plug and play model for companies to incorporate a specific dialysis pump that is commercially available and quickly integrate it into their system. The Simulink model was used to simulate the system behavior and analyze multi domain dynamic systems data. A mathematical representation of the physical system was derived using fluid dynamic equations. The mathematical equations were then translated into Simulink blocks for the computer environment to understand. A proportional integral derivative controller was designed and integrated into the system in order to compensate the flow rate for any difference between the flow set point and the actual flow. System monitors were developed to protect patients from hazardous conditions.

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Introdução: A terapia renal substitutiva por diálise peritoneal (DP) na doença renal crônica pode ser realizada manualmente pela DP ambulatorial contínua (CAPD) ou pala utilização de cicladoras automatizadas (APD). O impacto da modalidade de DP nos resultados clínicos, sobrevida do paciente, da técnica de diálise e risco de peritonite não foi avaliado por ensaios clínicos randomizados com alto número de pacientes. Estudos observacionais não mostraram de modo consistente, superioridade de um desses métodos. Objetivos: Comparar os resultados e desfechos clínicos do tratamento por CAPD e APD, em coorte de pacientes incidentes adultos e incluídos no Estudo Multicêntrico Brasileiro de Diálise Peritoneal (BRAZ-PD). Métodos: Estudo nacional de coorte prospectivo multicêntrico no qual foi incluídos pacientes incidentes com pelo menos 90 dias em DP. Os pacientes foram alocados em dois grupos, tratados exclusivamente por CAPD ou APD, utilizando-se o escore de propensão para pareamento dos mesmos, de acordo com as variáveis: idade, etnia, sexo, diabetes mellitus, índice de massa corporal, experiência do centro, biênio de início da DP, doença arterial coronária, doença arterial periférica, hipertensão arterial, presença de neoplasia maligna, tempo de escolaridade, renda familiar, tempo de acompanhamento pré-diálise e hemodiálise prévia. Os desfechos clínicos foram avaliados utilizando o modelo de risco proporcional de Cox e análise para riscos competitivos de Fine e Gray. A evolução dos dados bioquímicos, hemoglobina e pressão arterial foi comparada pelo teste t ou teste de Wilcoxon. Resultados: Após o pareamento, 1445 pacientes incidentes foram incluídos em cada grupo. O risco de morte por todas as causas (SHR1.44 CI95%1.21-1.71) e por causa cardiovascular (SHR1.34 CI95%1.03-1.73) foi maior nos pacientes em CAPD, mas não observamos diferença na sobrevida da técnica e tempo para o primeiro episódio de peritonite. As médias de concentração sérica de potássio e de fósforo foram menores nos pacientes em CAPD na maioria das avalições, não se observando diferenças no controle pressórico e das demais variáveis. Conclusão: Com base em um grande estudo de coorte, randomizado e prospectivo, não foram encontradas diferenças na falência da técnica e tempo para o primeiro episódio de peritonite entre a CAPD e APD. Por outro lado, a APD se associou a maior sobrevida do paciente em comparação com CAPD. Esses achados podem influenciar a escolha da modalidade e estimular uma mais ampla utilização da APD.
Introduction: Renal substitutive therapy by peritoneal dialysis (PD) in chronic kidney disease patients can be performed manually by continuous ambulatory PD (CAPD) or using automated cyclers (APD).The impact of PD modality on patient survival, technique failure and peritonitis rates is not fully understood, and no large-scale randomized clinical trial is available. Observational studies have failed to show superiority of one of PD modalities. Objective: The aim of this study is to compare the clinical results and endpoints between CAPD and APD, in a large nation-wide PD cohort, BRAZ-PD. Methods: This is a prospective cohort study that included all incident PD patients with at least 90 days of PD recruited in the BRAZ-PD study. All patients who were treated exclusively with either CAPD or APD were matched for different covariates (age, diabetes, BMI, center-experience, coronary artery disease, cancer, literacy, hypertension, race, previous hemodialysis, gender, pre-dialysis care, family income, peripheral artery disease and year of starting PD) using a propensity score calculated with the nearest neighbor method. Clinical outcomes analyzed were overall mortality, technique failure and time to first peritonitis. For all analysis we also adjusted the curves for the presence of competing risks with the Fine and Gray analysis. Biochemical data, blood pressure and hemoglobin levels were compared by test or Wilcoxon test. Results: After the matching procedure, 1,445 patients were included in each group. General (SHR1.44 CI95%1.21-1.71) and cardiovascular mortality risk (SHR1.34 CI95%1.03-1.73) were higher in CAPD patients, but no difference was observed for technique failure nor for time till the first peritonitis episode. The mean of serum and phosphorus concentration were lower in CAPD group in the majority of measurements. Conclusion: In the first large PD cohort study with groups balanced for several covariates using propensity score matching, PD modality was not associated with differences in neither time to first peritonitis nor in technique failure. Nevertheless, patient survival was significantly better in APD patients. These findings can influence the PD modality choice and encourage a greater APD utilization.

Orientador: Pasqual Barretti
Resumo: Introdução: A terapia renal substitutiva por diálise peritoneal (DP) na doença renal crônica pode ser realizada manualmente pela DP ambulatorial contínua (CAPD) ou pala utilização de cicladoras automatizadas (APD). O impacto da modalidade de DP nos resultados clínicos, sobrevida do paciente, da técnica de diálise e risco de peritonite não foi avaliado por ensaios clínicos randomizados com alto número de pacientes. Estudos observacionais não mostraram de modo consistente, superioridade de um desses métodos. Objetivos: Comparar os resultados e desfechos clínicos do tratamento por CAPD e APD, em coorte de pacientes incidentes adultos e incluídos no Estudo Multicêntrico Brasileiro de Diálise Peritoneal (BRAZ-PD). Métodos: Estudo nacional de coorte prospectivo multicêntrico no qual foi incluídos pacientes incidentes com pelo menos 90 dias em DP. Os pacientes foram alocados em dois grupos, tratados exclusivamente por CAPD ou APD, utilizando-se o escore de propensão para pareamento dos mesmos, de acordo com as variáveis: idade, etnia, sexo, diabetes mellitus, índice de massa corporal, experiência do centro, biênio de início da DP, doença arterial coronária, doença arterial periférica, hipertensão arterial, presença de neoplasia maligna, tempo de escolaridade, renda familiar, tempo de acompanhamento pré-diálise e hemodiálise prévia. Os desfechos clínicos foram avaliados utilizando o modelo de risco proporcional de Cox e análise para riscos competitivos de Fine e Gray. A evolução dos ... (Resumo completo, clicar acesso eletrônico abaixo)
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Les études regroupées dans cette thèse montrent qu'il existe une hétérogénéité entre les centres de dialyse péritonéale dans la survenue des infections péritonéales et l’échec précoce de la méthode. Nous avons aussi montré que certaines organisations peuvent être modifiées dans l’objectif d’améliorer le devenir du patient en optimisant la ressource.Nos travaux soulignent le rôle des équipes infirmières et l’importance des visites infirmières à domicile dans la prévention des infections du liquide de dialyse péritonéale. La mise à disposition de moyens humains minimum pourrait constituer un des critères d’attribution des autorisations de traitement par dialyse donnés aux établissements de santé.Augmenter la taille des centres pourrait avoir un effet bénéfique sur la survie de la méthode en améliorant l’expérience des centres. Dans ce contexte, le regroupement d’activité entre plusieurs établissements pourrait avoir un effet positif sur la survie de la méthode.Nous avons aussi pu observer qu’il existait une disparité entre les centres dans l’utilisation de l’assistance à domicile par une infirmière pour la réalisation de la dialyse. L’attribution de l’assistance repose principalement sur l’évaluation de l’infirmière de dialyse péritonéale ce qui laisse entrevoir des possibilités de rationalisation dans son utilisation. L’utilisation et la validation d’outils permettant d’estimer la capacité d’autonomisation du patient est une recherche qui devra être conduite
The studies grouped in this thesis show that there is a heterogeneity between the peritoneal dialysis centers in the occurrence of peritoneal infections and the early failure of the method. We have also shown that some organizations can be modified in order to improve the patient's future by optimizing the resource.Our work highlights the role of nursing teams and the importance of home nursing visits in the prevention of peritoneal dialysis fluid infections. The provision of minimum human resources could be one of the criteria for granting dialysis treatment authorizations given to health facilities.Increasing the size of the centers could have a beneficial effect on the survival of the method by improving the centers experience. In this context, group activities between several establishments could have a positive effect on the survival of the method.We also observed that there is a disparity between centers in the use of home assistance by a nurse for dialysis. The allocation of assistance is mainly based on the evaluation of the peritoneal dialysis nurse, which suggests possibilities of rationalization in its use.The use and validation of tools to estimate the patient's capacity to be treated by self-care peritoneal dialysis is a research that will need to be conducted

Cardiovascular disease is responsible for at least half of all deaths in end-stage renal disease patients on maintenance dialysis and is attributed to the very high prevalence of left ventricular hypertrophy and dysfunction, cardiac failure, coronary artery disease and other atherosclerotic complications. Apart from traditional risk factors such as smoking, hypertension, diabetes and dyslipidemia, these patients are at risk of accelerated atherosclerosis and other cardiovascular complications as a result of non-traditional risk factors such as inflammation, anemia, increased oxidative stress, hyperparathyroidism and excessive calcium phosphorus load. In recent years, there is an increasing recognition of calcification complications in patients on dialysis. However, the importance and prognostic value of calcification in patients on peritoneal dialysis is not known. Residual renal function has a significant contribution to the overall survival in patients on peritoneal dialysis but whether it is in any way related to cardiovascular death and complications in patients on peritoneal dialysis is not known. Inflammation is highly prevalent in dialysis patients and is considered to play a pathogenic role in cardiovascular disease. In this thesis, we evaluated some of these relatively novel factors that may predispose peritoneal dialysis patients to an increased risk of cardiovascular complications and mortality, including calcification, loss of residual renal function and inflammation. A number of important conclusions were drawn from these studies. First, valvular calcification is a marker of atherosclerosis and shows important associations with malnutrition and inflammation and is an important predictor of mortality and cardiovascular deaths in peritoneal dialysis patients. Second, inflammation, as denoted by either C-reactive protein or vascular cell adhesion molecule-1 shows an important association with residual renal function and cardiac hypertrophy and is associated with mortality and cardiovascular risk in peritoneal dialysis patients. Third, loss of residual renal function is an important cardiovascular risk and combines adversely with C-reactive protein and cardiac hypertrophy to increase cardiovascular mortality in peritoneal dialysis patients. Fourth, resting hypermetabolism and the malnutrition, inflammation and atherosclerosis syndrome are associated phenomena that parallel the decline of residual renal function and predict an increased mortality and cardiovascular death in peritoneal dialysis patients.

Introducción: En pacientes con Enfermedad Renal Crónica Terminal (ERCT), la mortalidad cardiovascular está asociada a la presencia de calcificaciones vasculares. Nuestro objetivo fue determinar la asociación entre la modalidad de diálisis y la presencia de calcificación en aorta abdominal en pacientes con ERCT. Métodos: Realizamos un estudio transversal mediante el censo de los pacientes de la unidad renal del Hospital Nacional Edgardo Rebagliati Martins (HNERM), Lima-Perú. Las calcificaciones se evaluaron con radiografías simples de abdomen lateral. Comparamos la proporción de sujetos con calcificaciones según modalidad de diálisis. Calculamos razones de prevalencia mediante la regresión log-binomial. Resultados: Enrolamos 224 pacientes de los cuales 75,4% (169/224) estaban en hemodiálisis y 24.6% (55/224) en diálisis peritoneal. La edad mediana fue 57 años y el 49.1% (110-224) eran mujeres. El 31.3% (70/224) tuvo calcificaciones en aorta abdominal. La modalidad de diálisis no presentó asociación significativa con la presencia de calcificaciones. Sin embargo, la significancia presento valores límites. Los niveles altos de paratohormona estuvieron asociados en forma independiente con las calcificaciones. Conclusiones: Nuestro estudio sugiere que la diálisis peritoneal podría asociarse a una mayor presencia de calcificaciones vasculares a comparación de la hemodiálisis por ser la significancia límite debido al pequeño tamaño muestral. La evaluación rutinaria de calcificaciones a lo largo del tratamiento de soporte dialítico debe ser promovida en esta población.
Background: Presence of vascular calcifications is associated to cardiovascular mortality in patients with terminal chronic renal disease (ESRD). The aim of the present study is to determine the association between dialysis modality and the presence of vascular calcification. Methods: Vascular calcification was detected by plain lateral abdominal radiograph. We calculated the proportion of vascular calcification associated whit dialysis modality obtaining adjusted prevalence ratios from logistic regression models in this cross- sectional study. Results: We studied a total of 224 patients, 75.4 % (169/224) were on hemodialysis and 24.6% (55/224) on continuous ambulatory peritoneal dialysis. The median age was 57 years –old and 49.1% (110-224) were female. Abdominal aortic calcification was detected in 31.3% (70/224). Higher parathyroid hormone level (PTH) was an independent factor associated whit vascular calcification. Conclusions: Our study suggests that peritoneal dialysis could be associated a higher presence of vascular calcification but we did not find a significance result due to small sample. The continuous evaluation in this group of patients must be encouraged to prevent further complications.

The primary intent of this thesis is to delineate the relative roles of local membrane and systemic consequences of peritoneal dialysis therapy, with particular reference to the role of inflammation and a severe, uncommon complication, encapsulating peritoneal sclerosis (EPS). Data sources comprised observational cohort studies as well as registry data: the Stoke PD study, a single centre study with clinical data, the Global Fluid Study (GFS), a multinational study with clinical data and repeated dialysate and plasma samples, and Scottish Renal Registry (SRR) and AnzData registry data. Through a cross sectional analysis of dialysate and plasma samples from GFS for inflammatory cytokines, we demonstrated that peritoneal and systemic inflammation are mostly separate processes although there is an association for IL-6 along with a steep concentration gradient from dialysate to plasma. Peritoneal inflammation, though IL-6, is the strongest determinant of peritoneal solute transport, and systemic inflammation, though IL-6, is a strong predictor of patient survival although peritoneal may contribute to systemic inflammation. Through a nested case control study of GFS we showed that inflammatory cytokines are upregulated within the peritoneum prior to developing EPS. With a nested case control design from the Stoke PD study, we showed that a decrease in ultrafiltration, likely due to increased fibrosis causing a reduction in osmotic conductance to glucose, also predisposes to EPS. A competing risks analysis of SRR and AnzData showed that patients at a high risk of death, have a low risk of EPS. These findings provide supporting evidence for the theory that the risk of EPS develops through the accumulation of inflammation-driven fibrosis due to dialysate exposure over a long period of time. Dialysate contains high concentrations of glucose and absorption of this drives impairment of systemic glucose metabolism, demonstrated through a cross sectional analysis of GFS.

Peritoneal dialysis (PD) is a life-saving form of renal replacement therapy for those with End Stage Kidney Disease. Peritoneal fibrosis is a considerable problem for PD patients, and mesothelial cells, which line the peritoneal cavity, play a central role in response to injury and fibrogenesis within the peritoneum. Mesothelial cells may undergo mesothelial to mesenchymal transition (MMT) contributing to peritoneal fibrosis and treatment failure. miRNAs are important regulators of fibrosis but their roles in peritoneal fibrosis are largely unknown. Here, a detailed characterization of the MMT process was performed in primary human mesothelial cells (HPMCs) in response to Transforming Growth Factor beta-1 (TGF-β1). Hybridization array showed mesothelial miR-21 and miR-31 expression was up-regulated by TGF-β1 which was validated by RTqPCR in different PD associated MMT models. Mesothelial cells cultured ex vivo from PD patients exhibited phenotypic changes consistent with a progressive MMT process that correlated with an increase in miR-21 and miR-31 expression. Association of miRNA expression and MMT markers in 33 peritoneal biopsies from patients undergoing PD treatment and in PD effluent from 230 PD patients confirmed these results. In silico analysis combined 4 target prediction algorithms (Targetscan, miRanda, miRDB and Diana-microT) for miR-21 and integrated the resulting outcome with mRNA arrays comparing omentum vs PD effluent-derived HPMCs with epithelial (E) and non-epithelial (NE) phenotype. 13 possible miR-21 targets during the MMT process associated to PD therapy were identified and model scrutinized. Four of these were confirmed to be miR- 21 targets. Functional gene analysis indicated that selected targets may be downstream modulators of Snail and cooperate driving MMT during peritoneal fibrosis. Taken together, these data provide a detailed characterisation of mesothelial miRNA expression and responses to TGF-β1, and identify miR-21 and miR-31 as promising biomarkers for peritoneal fibrosis associated to PD therapy.

Background: Peritoneal dialysis is a daily, life-saving treatment for end-stage renal disease, performed at home by patients and their relatives. Increasing numbers of patients are requiring treatment for this disease and therefore clinicians are calling for more patients to use peritoneal dialysis. However, the literature revealed only a small number of qualitative studies that considered patients’ experiences of their treatment, while a dearth of studies that explored relatives’ perspectives was noted. Aim and research questions: The study aimed to explore the experiences of patients and their families living with peritoneal dialysis. The specific research questions were: • What influences patients’ decisions to choose peritoneal dialysis? • How does peritoneal dialysis impact on life and the home environment? • How is peritoneal dialysis managed at home and integrated into everyday life? • How do families perceive having a relative with peritoneal dialysis at home and what contribution do they make to the process? Methodology and methods: The study employed ethnographic methodology and the methods included in-depth interviews and ethnographic observations with sixteen patients using peritoneal dialysis at home in Wales, and their relatives. Additionally seven specialist nephrology healthcare professionals were interviewed, who provided contextualising information about the care they give to patients and their families. The data were analysed thematically using Wolcott’s (1994) approach of description, analysis and interpretation. Findings: The sociological theory of illness trajectories was adopted as a conceptual framework, which guided the analysis and presentation of study findings. Participants reflected on the difficult process of choosing peritoneal dialysis, which was influenced by a preference for home, aversion to hospital and hope for control. The challenges of living with the treatment were described and observed, including medicalisation of the home, while participants tried to minimise their disrupted lives through creativity and flexibility. The future was associated with fear and uncertainty about deterioration, although participants maintained hope that they might receive a kidney transplant. Conclusions: Through the use of ethnography, this study revealed the challenges of living with peritoneal dialysis, but also the ability of families to integrate the treatment into everyday life. The study also demonstrated the usefulness of ethnographic methodology to explore how patients and their families live with home medical treatments.

Despite advances in treatment, peritoneal infection remains one of the main causes of technique failure in Peritoneal Dialysis (PD) patients. Understanding the nature of the peritoneum's response to inflammation is vital if we wish to reduce the negative impact of inflammation and infection on the peritoneal membrane. Given that aberrant leukocyte recruitment and activation appears to be a feature of these responses it is particularly important that we understand the contributions made by both resident and recruited peritoneal leukocytes in controlling this process as well as their direct contribution to membrane damaging events. Data presented in this thesis has shown that the peritoneal T-cell pool is a heterogeneous mixture of specialized T-cell subsets. In contrast to previous observations, we have shown that (under appropriate conditions) these cells are capable of being activated, though their effector function appears to be tightly regulated by peritoneal dendritic cells. The phenotype and activation threshold of peritoneal T-cells differs markedly from that of peripheral blood T-cells in that the peritoneal cavity is enriched in both effector memory and regulatory T-cells. These cells exist in a delicate equilibrium to both maintain homeostasis and ensure prompt removal of invading pathogens. During episodes of acute inflammation (peritonitis) further specialized T-cell subsets (TH17 and Vy9S2 T- cells) are recruited into the peritoneal cavity. These cells form part of the early immune response and are a pivotal link between the innate and adaptive arms of the immune response. Recurrent peritonitis has a detrimental impact on the function of peritoneal T- cells, impairing both the proliferation and effector function of these cells. This peritoneal T-cell dysfunction contributes to a state of immuno-suppression thus potentially rendering the patients more susceptible to further episodes of peritonitis. It is also likely to have a negative impact on immuno-resolution and contribute to neutrophil retention, chronic inflammation and membrane fibrosis.

Background Changes in the structure and function of the peritoneal membrane limit the duration of PD. Rarely (and unpredictably) these changes progress to severe fibrosis and bowel encapsulation (encapsulating peritoneal sclerosis, EPS) with substantial morbidity and mortality. Methods PD fluid and serum samples from 50 patients were added to 100 previously analysed samples (Dr S Ahmad). CCL18, IL-6, MCP-1 and angiogenin were measured by ELISA. CCL15 was measured for the first time in 125 serum and dialysate samples. Fifty one year follow up samples were analysed. Serum cytokines were measured in patients with and without EPS. Peritoneal mesothelial cells were cultured and media cytokine levels measured. CCL15 stimulation of cytokine production was investigated. Protein transfer across the peritoneal membrane by size was investigated. CT scans from 20 pre-EPS PD patients were scored and compared with scans of non-EPS patients. Results Levels of CCL18, MCP-1, CCL15, angiogenin and IL-6 in dialysate correlate with clinically important measures such as glucose exposure and D/P creatinine. Mesothelial cells in culture produce MCP-1, IL-6, angiogenin and CCL18. High dialysate levels of MCP-1, IL-6 and CCL15 are found in patients who subsequently developed EPS. High levels of CCL18 are also seen in haemodialysis patients with EPS. CT screening of PD patients used alone does not predict future EPS; in combination with abdominal symptoms CT scans may be of use. Conclusions There is local peritoneal production of chemokines such as MCP-1, CCL18, IL-6 and angiogenin, and the correlation of levels of these cytokines with clinically relevant parameters suggests they may be involved in the pathogenesis of long term changes in the peritoneum. At present neither clinical nor cytokine levels can reliably be used to predict future EPS. CT scanning may be helpful in patients at risk of EPS who develop new abdominal symptoms.

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

Background: End Stage Renal Disease (ESRD) is one of the commonest diseases in Hong Kong. Patient with ESRD needs to start dialysis for life maintenance. Peritoneal dialysis (PD) is the predominant dialysis modality for home dialysis patients. More than 80% of dialysis patients in Hong Kong receive PD. However, it also brings out some PD-related infectious complication such as tenckhoff exit-site infection, tenckhoff tunnel infection and PD peritonitis. These complications markedly contribute to treatment failure in PD patients. Especially PD peritonitis, it remains a leading complication of PD. Also it is a main cause of patients switch to haemodialysis (HD)and discontinue PD. Nevertheless, if the primary prevention of PD education do better, research evidences have shown that peritonitis infection rate of PD patients can be effectively reduced. It can be achieve by the utilization of effective education strategies and advanced training skills to enhance patients’ knowledge and skills of peritoneal dialysis. Purpose: This written proposal aims to identify the best evidence of PD education and to develop a guideline for this health education programme. The goal of the programme is to reduce the rate of PD-related infection for patients who started PD treatment at home after first CAPD training and education. Method: A total of 12 studies which focused on PD education and strategies for reducing PD-related infections were searched from electronic databases. Data extraction and critical appraisal were performed on these 12 studies. After the integrative review, the implementation potential was assessed. The results shown that the transferability of finding is high and it is feasible to conduct the proposed innovation. Then, the evidence-based guideline for PD education programme were developed and based on the high and medium level of evidence with grades of recommendation stated. Before implementing the proposed innovation, a communication plan was developed and targeted the various stakeholders (the administrators, nurses, patients and their relatives). The proposer would initiate the change and the programme leading group would guide and sustain the proposed innovation. The next process was planning a pilot study to examine the feasibility of the proposed innovation before implementation. Finally, different outcomes of the programme has been identified and evaluated in the evaluation plan. The methods for data analysis were formulated. Conclusion: The proposed peritoneal dialysis education programme with best evidences support is worthy to be adopted in the clinical setting for the beneficial of PD patients to reduce their PD-related infectious complications.
published_or_final_version
Nursing Studies
Master
Master of Nursing

Chronic kidney disease (CKD) is a multidimensional global health issue that can affect various individuals worldwide. Although renal transplantation is the preferred form of renal replacement therapy for most individuals with CKD, the lack of kidneys from suitable donors means that most of these individuals will not receive one. Many of these individuals living with CKD manage their kidney failure through peritoneal dialysis (PD) at home and under the guidance and support of nurses working with them in an outpatient clinic. Literature has suggested that healthcare providers perceive primary nursing as the ideal care delivery model for many patients and that the elements of primary nursing are correlated to improved patient outcomes. Although literature supports the use of primary nursing, there is very little known about this model from the perspectives of patients and the experiences of PD patients. The purpose of this study was to explore the nursing care experiences of PD patients managed by a primary nursing care delivery model and further understand the unique healthcare experiences of this population. Using interpretive description as a research methodology, 15 participants were purposefully sampled from an outpatient PD clinic and participated in one-on-one face-to-face interviews. Interviews were digitally audio-recorded and conducted using a semi-structured interview guide. Findings from the study illustrated that PD patients were not experiencing all of the elements associated with primary nursing. A modified form of primary nursing was being experienced by the patients in which they received individualized and comprehensive nursing care. The nursing care of the patients was underpinned by a philosophy of patient-centred care that emphasized relational engagement between patients and nurses. In addition, organizational influences of nursing care such as PD nurse availability and operational hours of the PD clinic contributed to the experiences of patients having to navigate through unforeseen challenges in their care. This study can inform future research involving the analysis of health outcomes for PD patients, understanding family perspectives, and exploring nursing leaders’ perceptions to further improve the nursing care experiences of PD patients.
Applied Science, Faculty of
Nursing, School of
Graduate

The aim of this study was to assess the possible benefits, in terms of nutritional state and morbidity, of improved correction of metabolic acidosis (MA) in the first year of treatment with peritoneal dialysis (PD). Two hundred consecutive new PD patients were randomised, in a single-blind fashion, to receive a high (HA: lactate 40 mmol/L) or low (LA: lactate 35 mmol/L) alkali dialysate, and studied for one year. At one year, the venous serum bicarbonate and arterial pH were 7.44 0.004 and 27.2 0.3 mmol/L in the HA group, and 23.0 0.3 mmol/L and 7.4 0.004 in the LA group (both p<0.001). At one year, the increase in body weight in the HA group (6.1 0.66 kg) was higher than in the LA group (3.71 0.56 kg) (p<0.05). The increase in midarm circumference in the HA patients (1.26 0.16 cm) was significantly higher than the increase in the LA patients (0.61 0.16 cm) (p<0.05). The increases in triceps skinfold thickness were not significantly different (HA: 2.5 0.41 mm vs LA: 1.24 0.38 mm; (p = 0.1). Serum albumin was 37.8 0.4 g/dl at one year in the HA group, and 38.2 0.5 g/dl in the LA group (NS). Dietary protein intake at one year (HA: 0.9 0.2 g/kg/day vs LA: 1.0 0.1 g/kg/day) was not significantly different. There were less hospital admissions in the HA group (1.13 0.16 per patient) compared to the LA group (1.71 0.22 per patient) (p<0.05). The HA patients spent less days in hospital than the LA patients (16.4 1.4 days vs 21.2 1.9 days; p<0.05). It is concluded that better correction of MA leads to greater increases in body weight and midarm circumference, but not triceps skinfold thickness, in the first year of PD. The improvement in morbidity, in terms of number of admission and days in hospital per year, may be associated with the improvement in nutritional state.

Although relatively rare, encapsulating peritoneal sclerosis (EPS) is nonetheless a major concern within the renal community. Risk of developing EPS is associated with long-term peritoneal dialysis. Surgery now offers better outcomes. Research into EPS continues to focus on imaging and early detection methods, genetics, biomarkers and preventive strategies. No previous studies have examined patients' experiences of EPS, or their perception of the effect of EPS on health-related quality of life. Aims: The aim of the present study was to explore the experience of patients who have undergone surgery for EPS in one centre in the north of England. Methods: Nine participants were recruited out of a total of 18 eligible. Most participants were interviewed twice conducted on two occasions over a 12-month period. This was October 2009 to October 2010. Analysis: Interpretative data analysis was conducted, following the philosophical tradition of hermeneutics. Following the first interview a summary was sent to each participant before the second interview. Both interviews were analysed and are presented as themes. Results: EPS presents the biggest challenge these patients have had to face since developing chronic kidney disease. Three major themes were identified each with subcategories: 1. Understanding EPS -self interpretation, 'not being heard', gaps in information and knowledge, diagnosis shock and relief-confronting death 2. EPS an embodied experience- endurance, bodily awareness from others and within, struggles with eating 3. Adjustments and Transitions 'A journey of survival'- losses, support structures and their impact and locating self. Conclusions: The findings of this study highlight a number of important issues relevant to clinical practice, including lack of information and understanding of EPS, particularly its early symptoms, the extent of the surgery and the support required. At the time patients transfer from peritoneal to haemodialysis, the provision of adequate information about the risks and potential early signs of EPS may improve not only their experiences but in addition may assist its early detection.

Despite advances in treatment, peritoneal dialysis (PD)-associated peritonitis remains a major cause of morbidity and mortality in PD patients. Given that peritonitis can be the proximate cause of technique failure and cause ultrafiltration failure at a later time, it is important to understand the peritoneal immune response, microbiology and outcomes of these infections. Data presented in this thesis have shown that leukocytes are recruited to the peritoneal cavity, starting with a rapid accumulation of neutrophils, which are later replaced by a population of mononuclear cells, including monocytes/macrophages and T cells during acute peritonitis. Of note, Vγ9/Vδ2 T cells are also recruited to the peritoneal cavity in the early stage, which implies a significant role of Vγ9/Vδ2 T cells as early responders in acute peritonitis. In patients with acute peritonitis, the capacity of the causative pathogen to produce (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), together with the infiltration of activated Vγ9/Vδ2 T cells are important risk factors and possible predictors of patient outcomes from infection. By performing a detailed immunological and microbiological analysis in PD patients on the first day of peritonitis, our findings provide proof of concept that acute bacterial infections indeed leave characteristic disease-specific ‘immune fingerprints’ of diagnostic and prognostic value. Local fingerprints not only discriminated between episodes of culture-negative and culture-positive PD-associated peritonitis but also predicted infections caused by Gram− or Gram+ bacteria. HPMC play an important role in maintaining homeostasis of the peritoneal immunity. Our data revealed the regulation of Vγ9/Vδ2 T cells by HPMC and demonstrated that resting HPMC were potent suppressors of Vγ9/Vδ2 T-cell cytokine production and proliferation in the presence of HMB-PP. Collectively, these findings improve our insight into the complex cellular interactions in PD-associated peritonitis and peritoneal homeostasis, identify novel biomarkers of possible diagnostic and predictive value and highlight new avenues for therapeutic intervention.

Dissertation in fufillment of the degree of MSc(Med), Faculty of Health Sciences, University of the Witwatersrand
Introduction: Measurement of small solute clearance is the objective means of quantifying dose of peritoneal dialysis (PD) and various organisations have issued guidelines on target values. Assessment of PD adequacy involves other factors such as blood pressure control, anaemia management, mineral metabolism, nutritional status and ultrafiltration. Membrane transport characteristic is important for PD prescription on an individual patient basis and is related to patient outcome. In this study the adequacy of PD, using small solute clearance measurement as well as other factors, and membrane characteristics have been assessed and classification of patients using our own reference values is reported for the first time. Nutritional status has been studied and the use of simple tools such as the subjective global assessment has been validated for use in our patients. Materials and Methods: A cross sectional study involving 80 adult continuous ambulatory peritoneal dialysis (CAPD) patients. Peritoneal equilibration test (PET) was performed to assess the membrane characteristics; 24 hour dialysate fluid and urine samples were collected and used for the measurement of solute clearance, while nutritional status was assessed using the subjective global assessment (SGA) instrument, anthropometric measurements and serum albumin estimation. Results: The mean age was 38 ± 12.43 years, 42.3% were females and 86% were blacks. Mean duration on CAPD was 19.8 ± 20.67 months. The mean of 4 hour D/P creatinine was 0.74 ± 0.13 and based on this, 18% were high transporters, 33.8% high average, 36.9% low average and 12% low transporters. Mean kt/v urea was 1.72± 0.32, and the recommended level of 1.7 was achieved by 62.8% of the patients. Mean haemoglobin was 10.99 ± 2.14 g/dl and the recommended target value of 11-12g/dl was reached by 55.8% of the patients. The mean BMI vi was 24.76 ± 3.50, mean Mid Upper Arm Circumference (MUAC) was 28.53±3.89 cm and mean serum albumin was 37.10 ± 7.6 g/l. Based on SGA scores, 42% of our patients were well nourished, 50% moderately undernourished while 8% were severely malnourished. We noted significant correlations between SGA score and BMI and MUAC while there was none with serum albumin level. The mean serum calcium and phosphate levels were within normal though the mean PTH level was higher. Conclusion: The D/P creatinine at 4 hours was higher than those reported in the literature, though the distribution of the transport types was similar. The recommended targets of kt/v and haemoglobin were achieved by the majority of our patients. Mineral metabolism parameters were within normal range. Malnutrition is common and SGA is a reliable method for nutritional assessment in our patients.

碩士
國立臺灣大學
護理學研究所
87
The purposes of this presence study were to understand the performance of dialysis techniques in which the arrangement of home environment, the executive of dialysate exchange, and the executive of exit-site care were performed daily by the home dialysis patients. The demographic backgrounds, the history and background of executive peritoneal home dialysis, infection rates, and self-efficacy on the executive home dialysis were also explored their effects on the above three home peritoneal dialysis executive behaviors. The purposive sampling method was used and 45 patients were recruited from the peritoneal dialysis center of a medical center in Taiwan. All subjects filled the Executive Home Dialysis Self-Efficacy Scale on their monthly scheduled OPD visits. All subjects were videotaped their performance of peritoneal dialysis techniques and environment prepared for the home dialysis at home by the researcher. The Home Peritoneal Dialysis Executive Behaviors Scale was used to score the executive behaviors from the videotapes. Results of the study showed that infectious complications remain the Achilles heel of peritoneal dialysis therapy and one fourth subjects had have peritoneal infections. The home environment arrangement had the highest score than the dialysate exchange technique, and the exit-site technique had the lowest score. Age and self-perceived efficacy on the executive home environment arrangement were the two factors affected the environment arrangement for home dialysis. The duration of the peritoneal dialysis and the better self-efficacy on the dialysate exchange technique affected the executive of dialysate behaviors. The self-perceived efficacy on the executive of exit-site care was the only factor affected the executive exit-site care behavior. The infection rate and three of the above home dialysis behaviors had significant related; however, the higher frequencies of infection rate of the patients have had, the lower total score of the home dialysis executive behaviors they had. In conclusion, the findings of this present study can help nursing professionals to better understand the relationships among demographic variables, therapeutic situation, infection rate, self-efficacy and home peritoneal dialysis executive behaviors on patients with home peritoneal dialysis. Further, it would advance nurse''s competence of helping patients to increase the self-efficacy, which is the key to improve the physical hygiene and home dialysis techniques, and then it may to decrease the frequency of infectious complications. Key words: peritoneal dialysis, home peritoneal dialysis executive behaviors, home dialysis techniques.

博士
臺灣大學
臨床醫學研究所
98
Background Both the prevalence and incidence of end-stage renal disease in Taiwan are the highest in the world. In 2007, the patients receiving dialysis were 52,537 persons in Taiwan. The prevalence was 2,288 per million population and the incidence was 415 patients per million population. According to the statistic data of Bureau of National Health Insurance (BNHI), dialysis therapy cost more than 330 billion NT dollars every year. In average, each dialyzed patient would spend 600 thousand NT dollars every year which is 30 times of the mean of general population. To reduce the medical cost on dialysis, BNHI promotes peritoneal dialysis as a long-term renal replacement modality. However, peritoneal dialysis patients will use high glucose content peritoneal dialysate to achieve ultrafiltration goal whenever they receive this renal replacement modality. Combine with other bio-incompatible factors in the peritoneal dilysate, peritoneum will be damaged by the dialysate and the metabolism of glucose and lipid will be affected by the dialysate in the long run. For these disadvantages of present dialysate, we conducted a serial of studies to investigate the long term complications of peritoneal dialysis. The effects of peritoneal dialysate was divided into two major portions: the first was the clinical effects of high glucose concentration in dialysate on patient survival, technique survival and metabolism in peritoneal dialysis patients. The second was local effects of bio-incompatible peritoneal dialysate on the peritoneum and their possible resolutions. For the long-term effects of peritoneal dialyate, we proposed that glucose content in peritoneal dialysate may result in unfavorable changes on peritoneal character and worsened metabolic profiles. We conducted a retrospective cohort analysis to investigate the impact of initial glucose load on long-term outcomes of peritoneal dialysis patients. In addition, since usage of high glucose concentrations in peritoneal dialyate may result in unfavorable results. We further conducted a study to analyze the factors associated with high glucose load in long-term peritoneal dialysis patients in each year. For the metabolism of glucose and lipid, adiponectin, a cytokine with anti-inflammatory properties that is secreted from adipose tissue, is associated with insulin resistance. It has been demonstrated that adiponectin is a predictor of cardiovascular events in both the general population and patients undergoing hemodialysis, however, its role in peritoneal dialysis patients remains unclear. For the local effect on peritoneum per se, peritoneal fibrosis is a common complication among long-term peritoneal dialysis patients including simple sclerosis and encapsulating peritoneal sclerosis. Encapsulating peritoneal sclerosis is a catastrophic complication of peritoneal dialysis patients. Tamoxifen and steroid are used to treat encapsulating peritoneal sclerosis but there is still limited experience about the therapeutic duration and outcome management. We provide a case series experience of treating encapsulating peritoneal sclerosis patients by using combination therapy of tamoxifen and steroid. Tamoxifen has successfully been used in treating encapsulating peritoneal sclerosis as well as other chronic fibrosis disorder, however, the mechanism of tamoxifen in treating encapsulating peritoneal sclerosis remains unclear. This issue deserve us to do further investigation. Methods In patient survival analysis, a total of 90 patients newly started on peritoneal dialysis were enrolled. All subjects were divided into low, medium, or high glucose load equally in patient number according to the average dialysate glucose concentration prescribed in the first 6 months from peritoneal dialysis initiation. Cox’s regression was used for survival analyses and linear regression was used for analyses of determinants for glucose load. In addition during the following up of these 90 newly-started peritoneal dialysis patients were surveyed for 5 years. We obtained glucose load by calculating annual glucose weight and dialysate volume that were administered. We conducted multiple linear regression analyses with time-dependent covariates to determine factors that influence the annual average dialysate glucose concentration. For analyzing the metabolic effects of adiponectin, serum adiponectin levels, measured using enzyme-linked immunosorbent assay in subjects with normal renal function and patients undergoing hemodialysis or peritoneal dialysis (28 subjects in each group), were analyzed to establish the relationship between adiponectin and lipid levels as well as insulin resistance. In the second study, 104 peritoneal dialysis patients were recruited to analyze the relationships between serum adiponectin level and residual renal and peritoneal function and C-reactive protein level. Independent factors for serum adiponectin level were determined from multiple linear regression. In treating the local effects on peritoneum of long term peritoneal dialysis, encapsulating peritoneal sclerosis patients were enrolled from two medical centers in northern Taiwan between 2005 and 2009. The diagnosis of encapsulating peritoneal sclerosis was made by clinical presentations of ileus and specific image findings. Tamoxifen and steroid were initiated after diagnosis. All medical records and individual laboratory data were reviewed. For investigating molecular mechanism of antifibrotic effects of tamoxifen, a bleach induced peritoneal fibrosis rat model was applied as the in vivo treatment target. Tamoxifen was intraperitoneally injected daily to treat peritoneal fibrosis. The peritoneal fibrosis scores and thickness of the submesothelial zone over the liver surface were measured as indicators for the severity of PF. Besides, human peritoneal mesothelial cells were used as an in vitro model to test the antifibrotic effect of tamoxifen. Gene expressions of transforming growth factors beta, connective tissue growth factor and collagen were investigated using quantitative polymerase chain reactions. Results In analysis of effects of glucose load, the mean follow-up period was 40.1 ± 11.8 months. Patients with higher glucose load showed a significantly worse cumulative technique survival (log rank p=0.002). In Cox’s regression analysis, patients with lower glucose load had significantly better technique survival (p=0.035). In linear regression analysis, preexisting diabetes mellitus (p&lt;0.001), lower serum albumin (p=0.012), and lower weekly renal Kt/V (p=0.019) were significantly correlated with higher glucose load. In analyzing the dterminants of glucose load in each year, there were 47 men and 43 women and the mean age was 53.4 ± 13.9 years. The technique survival rates were 91.0%, 84.1%, and 77.6% for beginning of the second, third, and fourth year of peritoneal dialysis therapy, respectively. The presence of diabetes mellitus, high body mass index (BMI), and low weekly renal Kt/V were significantly correlated with high average glucose concentration of the dialysate during the first, second, and third years. For patients undergoing peritoneal dialysis for more than 3 years, residual renal function deteriorated, and only diabetes significantly affected higher glucose concentration of the dialysate in the fourth year. For analyzing the impacts of adiponecctin on peritoneal dialysis patients, No significant difference was demonstrated comparing the serum adiponectin levels of peritoneal dialysis and hemodialysis patients, however, both were significantly higher than that of the control subjects (p&lt;0.01). Negative associations were demonstrated between adiponectin, and triglyceride (p&lt;0.01) and insulin levels (p&lt;0.05), and homeostatic model assessment of insulin resistance (HOMAIR) (p&lt;0.01) for the former two groups, however, a positive association was demonstrated for high density lipoprotein (p&lt;0.05). Neither hemodialysis nor peritoneal dialysis removed adiponectin significantly, with levels for the latter group negatively associated with residual renal function (p&lt;0.01) and C-reactive protein (p &lt; 0.001). Peritoneal dialysis patients using glucose-lowering agents had lower adiponectin levels, however, lipid-lowering agents and renin-angiotensin blockades did not appear to affect them. The independent determinants for serum adiponectin level in peritoneal dialysis patients were triglyceride, hemodialysis, CRP, and BMI, after adjustment for age, sex, peritoneal dialysis duration and diabetes. Adiponectin levels were not associated with left-ventricular mass or ejection fraction, however. In treating encapsulating peritoneal sclerosis, there was a total of 10 encapsulating peritoneal sclerosis patients (M/F: 3/7) with a mean age of 47.8 ± 9.6 years and a mean peritoneal dialysis duration of 8.7 ± 3.8 years. Refractory peritonitis was the preceding event in nine patients. Tamoxifen 10 mg twice daily and steroid equivalent to 0.5-1.0 mg/Kg/day were administered. Eight patients showed improvement of enteral feeding within 1 week of treatment but two of them died in the following period (nine days and seven months respectively). One patient achieved a partial improvement of clinical symptoms after two weeks of therapy and one patient was refractory to this regimen. Complications of this regimen such as gastrointestinal bleeding, perforation, and myocardial infarction mostly resulted from the steroid therapy. The study of molecular mechanism of antifibrotic effects of tamoxifen showed that tamoxifen could reduce the peritoneal fibrosis severity and submesothelial zone in bleach induced rat peritoneal fibrosis model. In HPMC, tamoxifen showed paradoxical effects between collagen I and TGF-β. Tamoxifen also inhibited TGF-β induced collagen and CTGF. Conclusion Form our serial studies, for the long term survival, higher glucose load during initial period of peritoneal dialysis was associated with higher prevalent diabetes, lower serum albumin, and lower residual renal function, and effectively predicted worse survival of peritoneal dialysis therapy. Patients with diabetes, high body mass index, and low residual renal function were more likely to require high glucose load for peritoneal dialysis therapy, especially during the first 3 years. After 3 years of peritoneal dialysis, diabetes was the only significant factor that determined a need for higher glucose load. In order to decrease the glucose load in chronic peritoneal dialysis patients, alternative osmotic agents such as icodextrin or amino acids should be considered in the daily peritoneal dialysis regimens. For the adiponectin, as for the hemodialysis patients, the peritoneal dialysis subjects had high adiponectin levels, not removed effectively using either of the studied dialysis modalities. In addition to a significant relationship with the components of insulin resistance, adiponectin was associated with CRP in these patients. These results indicate that adiponectin level in peritoneal dialysis patients may be a good indicator of cardiovascular disease risk. For treating encapsulating peritoneal sclerosis, the combination of tamoxifen and steroid is effective in ameliorating encapsulating peritoneal sclerosis symptoms in 80% of the patients. Chronicity of encapsulating peritoneal sclerosis might predict a treatment failure. Steroid could be tapered off if symptoms improve. And the possible antifibrotic effect of tamoxifen is through inhibiting CTGF to block collagen synthesis, although it enhances TGF-β which increases fibrosis. These results provide a possible molecular mechanism for tamoxifen.

博士
國立陽明大學
臨床醫學研究所
93
Infectious peritonitis is the most serious complication of peritoneal dialysis (PD), and may lead to peritoneal fibrosis and compromise the efficiency of dialysis. Peritonitis is a local inflammatory disorder. Recruitment and infiltration of leukocytes are essential elements of the peritoneal immune response. However, information on the role of T lymphocytes in peritoneal immunity is limited. The purpose of this study is to clarify the role of T lymphocytes in peritoneal defense mechanisms, and their influence on the response to the treatment of peritonitis and on its prognosis in patients undergoing PD. Four series of experiments were conducted in this study: First, we examined the changes in T-cell subpopulations and cytokine messenger RNA (mRNA) expression patterns during peritonitis in patients treated with PD. These observations were correlated with responses to treatment and with outcomes. Secondly, to determine the influence of peritonitis on peritoneal transport properties and peritoneal fibrosis, we studied the peritoneal dialyzing function and expression pattern of transforming growth factor-��1 (TGF-��1) as a marker of prognosis. Thirdly, To further explore longitudinal changes of peritoneal immunity during PD-related peritonitis and their influence on peritoneal T-cell differentiation, we examined the production of interleukin (IL)-12, IL-18, and interferon-�� (IFN-��) in peritoneal dialysate effluents (PDE) and the kinetics expression of the transcription factors T box expressed in T-cells (T-bet) and guanine adenine thymine adenine binding protein 3 (GATA-3) in peritoneal T cells during peritonitis. Finally, to explore the role of T lymphocytes in peritoneal immunity in cellular level, we examined the interaction between T cells and human peritoneal mesothelial cells (HPMC) by adhesion model and transmigration assay. The expression of integrins were investigated also. The results showed that the major T-cell phenotypes in PDE during peritonitis were T helper 1 (Th1)-CD4+ and T cytotoxic 2 (Tc2)-CD8+. The serial changes in T-cell subsets in PDE during peritonitis showed two patterns: a progressive increase in the CD4/CD8 ratio in PDE associated with a rapid response to treatment; and a progressive decrease in the CD4/CD8 ratio associated with a delayed response to treatment. A progressive decrease of the CD4/CD8 ratio in PDE correlated with a persistent expression of TGF-��1, and played a pathogenetic role in the evolution of peritonitis, peritoneal equilibration test (PET) deterioration and peritoneal fibrosis. In the early phase of peritonitis, IL-12, IL-18 and IFN-�� levels in PDE were significant greater in the rapid-response group. In the rapid-response group, IFN-�� and T-bet mRNA expression in peritoneal T cells increased, whereas that of GATA-3 decreased over time. Result were opposite in the delayed-response group. In cellular level, we demonstrated that integrins ��6��1 and ��4��1 mediated T cells adherence to and migration across monolayer of HPMC. This study explores the role of peritoneal T lymphocytes in peritoneal immunity during PD-related peritonitis. These results suggest that patterns of CD4/CD8 T-cell ratio in PDE predict the outcome of peritonitis in patients undergoing PD. These data also suggest local IL-12 and IL-18 production is part of a protective early immune response to PD-related peritonitis. High IL-12 and IL-18 levels in PDE during the early phase of peritonitis correlated with a predominant type 1 immune response and favorable outcome. Furthermore, the results of in vitro study show the potential role of integrins to control and modulate peritoneal T cells immune response. This study enhances our understanding of mechanisms of peritoneal immunity and also offers the target pathway in immunotherapy for PD-related peritonitis.

Literature review A literature review of the stability of antibiotics in peritoneal dialysis fluids was conducted. The information obtained was collated and presented in a format which would serve as a useful working reference for hospital pharmacists. It was found that the stability of antibiotics in peritoneal dialysis fluids had received little attention in the literature. The review highlighted the lack of information on the stability and compatibility of many of the antibiotics and antibiotic combinations commonly used for the treatment of peritonitis. Despite increasing interest in intraperitoneal antifungal chemotherapy, there was no information on the stability of antifungal agents in peritoneal dialysis fluids. Stability studies A study of the stability of the antifungal agent, miconazole, in peritonealdialysis fluid was conducted. Greater than 10% loss of the initial miconazole concentration occurred within 4 hours when this drug was added to peritoneal dialysis fluid and stored in polyvinyl chloride (PVC) bags at 20°C. Similar admixtures were stable for at least 3 days when stored in glass ampoules under the same conditions. These findings indicated that the loss of miconazole observed in PVC bags was due primarily to an interaction with the container, rather than chemical decomposition in solution. Approximately 28% of the miconazole lost from the solution was recovered from the plastic by methanolic extraction, representing sorption of miconazole by the PVC container. In the clinicalsituation, the rapid loss of miconazole from peritoneal dialysis fluid stored in PVC bags, would demand that such admixtures be prepared immediately prior to administration. A study of the stability of both components of the antibacterial combination, co-trimoxazole, in peritoneal dialysis fluid was conducted. Greater than 10% loss of the initial trimethoprim concentration occurred within 3 days when admixtures of co-trimoxazole in peritoneal dialysis fluid were stored in PVC bags at 20°C. The concentration oftrimethoprim in similar admixtures stored in glass ampoules under the same conditions, remained virtually unchanged for 9 days. This suggested that the loss of trimethoprim observed in admixtures stored in PVC bags, may have been due to an interaction with the container. Greater than 10% loss of the initial sulphamethoxazole concentration occurred within 2 days in admixtures stored in PVC bags. Similar losses occurred in admixtures stored in glass ampoules, suggesting that the mechanism of this loss was primarily chemical decomposition in solution. Further evidence for this proposition, was the time dependent increase in concentration of an unknown decomposition product in admixtures stored in both plastic and glass containers. It was suspected that this compound was a derivative of sulphamethoxazole, however it was demonstrated that it was not sulphanilic acid or 5-methyl-3-isoxazolamine, which have previously been identified as decomposition products of sulphamethoxazole under acid conditions. This study found that the shelf-life of admixtures of co-trimoxazole in peritoneal dialysis fluid stored in PVC bags at 20°C, was limited by the stability of the sulphamethoxazole component. The data conservatively indicated a shelf-life of approximately 12 hours, since greater than 10% loss of the initialsulphamethoxazole concentration had occurred in this time in one of the admixtures examined.

by Szeto, Cheuk Chun.
Thesis (M.D.)--Chinese University of Hong Kong, 2001.
Includes bibliographical references (p. 183-206).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.

博士
國立陽明大學
臨床醫學研究所
91
Background: Peritoneal dialysis (PD) is a widely used renal replacement therapy modality for end-stage renal disease patient. Patients receiving PD have higher technical failure rate than that of hemodialysis patients. Repeated peritonitis and ultrafiltration failure after long-term use of bio-incompatible peritoneal dialysate are two main reasons of technical failure. Peritonitis in PD patients is characterized by prolonged repair and was believed to cause peritoneum damage due to chronic inflammation. However, peritoneal mesothelial cells have good proliferating ability. Therefore, what is the reason of prolonged repair of peritoneum in PD peritonitis? We try to investigate the significance of human peritoneal mesothelial cells (HPMC) apoptosis during peritonitis and the role of nitric oxide, Fas-Fas ligand system in the process of peritoneal mesothelial cells apoptosis. Methods: We use cytokines (Tumor necrosis factor-a (TNF-α) 、Interleukin-1b (IL-1b)、Interferon-g (IFN-γ) 及lipopolysaccharide (LPS)) singly or in various combinations to stimulate HPMC and scrutinize the expression of nitric oxide synthase type II (iNOS) by western blot, reverse transcriptase polymerase chain reaction and Griess method. HPMC apoptosis was investigated by propidium iodide staining and TUNEL method. We also studied the expression of Fas in HPMC by flow cytometry and use anti-Fas antibody (clone CH11) to stimulate cytokine-primed HPMC. Apoptosis of HPMC was demonstrated by propidium iodide, TUNEL method and M30 cytodeath antibody staining. The quantity of apoptosis was studied by flow cytometry. The activities of caspase-3, caspase-8 and Bcl-2 were investigated by western blot. The apoptotic HPMC were co-incubated with adhered macrophages to see if macrophages could engulf apoptotic HPMCs. The peritoneal dialysate effluents of PD peritonitis patients were studied for the presence of apoptotic HPMCs. Results: Our results showed that iNOS is inducible after concomitant stimulation of TNF-a (5ng/ml) and IFN-g (5ng/ml). However, endogenous production of nitric oxide did not lead to apoptosis of HPMC. On the other hand, pre-incubation of HPMC with TNF-a (5ng/ml) and then stimulation with anti-Fas antibody (clone CH11) cause apoptosis of HPMC. Activation of both caspase-8 and caspase-3 were noted during the apoptotic process. The addition of caspase inhibitor could prevent the occurrence of apoptotic process. The apoptotic HPMC could be engulfed by macrophages. We found increased mesothelial cell apoptosis in peritoneal dialysate effluent during recovery phase of peritonitis. Conclusions: Our results reveal that bio-incompatible peritoneal dialysate probably aggravate the magnitude of HPMC apoptosis or affect the removal of apoptotic HPMC by macrophages during peritonitis. Failure to clear apoptotic HPMC might prolong peritoneal inflammation and therefore hamper the repair of peritoneum. The apoptosis of HPMC is related to the regulation of inflammation and subsequent repair of peritoneum during peritonitis.

Despite the decreasing incidence of peritoneal dialysis (PD) peritonitis over time, its occurrence is still associated with adverse outcomes. This thesis focuses on determining factors associated with PD peritonitis in order to facilitate identification of patients at risk. Using data collected in a multicentre Canadian database between 1996 and 2005, the study population comprised 4,247 incident PD patients, of whom 1,605 had at least one peritonitis episode. Variables independently associated with peritonitis included age [rate ratio (RR) 1.04 per decade increase, 95% CI 1.01-1.08], Black race (RR 1.37, 95% CI 1.00-1.88) and having transferred from hemodialysis (RR 1.24, 95% CI 1.11-1.38). There was an interaction between gender and diabetes (p=0.011), with an increased peritonitis risk only among female diabetics (RR 1.27, 95% CI 1.10-1.47). Choice of continuous ambulatory PD vs. automated PD did not influence peritonitis risk. These results contribute to our understanding of peritonitis risk among PD patients.

碩士
中國醫藥大學
醫務管理學研究所碩士班
97
Objectives：The nephritis, nephritic syndrome and nephrosis are altogether ranked eighth among ten leading causes of death today; however, the cost of dialysis care is rated as the number one among the health care expenditures and has become a huge burden for the National Health Insurance in Taiwan. Most literatures focused on the differences in expenses for various dialysis treatments.The purpose of this study is to examine the cost-effectiveness analysis (CEA) of hemodialysis (HD) and peritoneal dialysis (PD) from the perspective of the Bureau of National Health Insurance. Method：The sources of information, monitored about five to eight years individually, are based on the records of incident dialysis patients from the health insurance database, 1998 through 2007. Both t-test and ANOVA statistics techniques are applied to tell the differences of the average of total cost and survival weeks between HD and PD;thereafter, the CEA is also used to figure out the average survival expense per week for different kinds of dialysis therapy. Results：The percentage of female patients was slightly higher than male among 2600 new initiated dialysis therapy cases. The mean ages for HD and PD were 62 and 52 years old respectively and the survival rates of HD and PD were similar. Survival rates of diabetes and/or hypertension patients were lower than disease-free ones. The average of total cost for HD was significantly higher than that for PD on control demographic factors in age group (P < 0.05); however, the survival rates were not significantly. The average of total cost for diabetes patients of HD was significantly higher than that for diabetes of PD on control demographic factors in age group (P < 0.05). The result of CEA shows that PD is more cost-effectiveness than HD on control demographic factors and comorbidity, i.e. the cost of survival required each week for HD is higher than that for PD. Conclusions：Overall, after five to eight years follow-up period, the study shows that PD is the treatment with better cost-effectiveness; therefore, we suggest that initial dialysis patients with PD will be more cost-effectiveness.