Dissertations / Theses on the topic 'End Stage Kidney Disease (ESKD)'

Introduction This study was carried out in Ghana, where the incidence of end stage kidney disease (ESKD) is increasing in a context of limited treatment options. Understanding the issues patients with ESKD grapple with when diagnosed with this life-threatening condition is essential to improve healthcare policy and practice in such low- and middle-income settings. In the absence of evidence related to the African ESKD patient journey, this study aimed at exploring how decisions about ESKD management are being made, especially in under-resourced settings where specific treatment modalities are not always available. The study addresses an important gap in the literature concerning choice and decision making in an international context. The key research question for this study is, in terms of the context, does the problem of limited resources in low- and middle-income countries present different choices to the patient with ESKD facing decisions about their treatment? Methodology and Methods The study employed a qualitative research design, using grounded theory methodology. Twenty-seven participants in three renal centres, comprising twenty-two patients with ESKD and five clinicians, were selected using the theoretical sampling approach and interviewed for this study. Constant comparative analysis was employed in data analysis. Results A conceptual map depicting the ESKD patient journey and key phases of decision making was developed from this study. Ghanaian patients with ESKD are mostly unaware of the implications of their initial symptoms, and end up delaying seeking healthcare from a hospital. Some of those who seek care from hospitals are initially diagnosed with and treated for other conditions other than ESKD. Thus, many patients with ESKD in Ghana present late to a renal centre. Treatment for ESKD is initiated for various reasons, including, initially, the urgent need to avoid premature death. Many approach their condition in terms of hoping for a cure and do not always understand the chronic nature of their condition. Decisions on initiating haemodialysis (HD) are mostly shared between clinicians and patients and/or their families but the process is mainly driven by the need to ascertain patient and family’s ability to finance HD, rather than considering other aspects of treatment burden. The subject of death or conservative management is not openly discussed and, once this is brought up, patients usually do everything possible to opt for another form of treatment, including the simultaneous use of other non-RRT and traditional or faith-based healing approaches. Clinicians play vital roles in the decision making of patients with ESKD although they have general feelings of helplessness while supporting these patients. Convergence between individuals’ experiences of realities of living with and managing ESKD, and support from clinicians in the renal setting ultimately leads to a reconstruction of health expectations that commensurate management goals of ESKD. This sums up the substantive theory of ‘reconstructing health expectations’ that was generated from this study. Conclusions Financial and geographical inaccessibility of renal replacement therapy (RRT) as well as the relative lack of biomedical treatment choices make decision making daunting for the individual with ESKD in Ghana. Reluctance to discuss death as a potential outcome is a hindrance to the consideration of conservative management as a treatment option. Effective realignment of healthcare policies to address changing patterns of diseases is necessary to contribute to prevention, early detection and effective management of ESKD in the country. An improved approach to conservative management is urgently required, including training support for clinicians on shared decision making as well as sensitisation of patients on this modality.

There has been an increasing recognition over the last ten years of the importance of integrating palliative care alongside other aspects of care for people with life-limiting illness including kidney disease. Over the same time period, policy initiatives have aimed to address and improve the end of life care for all adults with kidney disease. However, little is known about the transitions experienced by people with end-stage kidney disease (ESKD) as they approach the end of life. This qualitative study explored the transitions experienced by people with ESKD as they approached the end of their lives. A constructivist grounded theory methodology was used, and unstructured interviews were conducted with twelve people living with ESKD who were deemed to be approaching the end of their lives. The interview data were analysed and interpreted using the constant comparative method. The core category of ‘restructuring reality’ emerged from the data analysis alongside three dynamic, interrelated conceptual categories and the subcategories within these. These conceptual categories were: ‘striving to maintain autonomy and control in decision making’, ‘managing uncertainty: knowing without clarity or confirmation’, and ‘the importance of personal virtues in transitioning through the illness’. The substantive theory which emerged from the data analysis and which conceptualised the process and experience of transition for people with ESKD in this study was defined as 'the restructuring of reality during transition for people with ESKD approaching the end of life’. The study findings provided valuable insight into the experience of people with ESKD as they approach the end of their lives. The tentative theory presented in this study added to the knowledge of the transitions experienced by people with ESKD as they approached the end of their life. The theory captured how participants made sense of and adjusted to the changes they experienced as their health deteriorated; it emphasised that being able to continue to contribute and be involved in decision-making about care was an important aspect of the transition process as people approached the end of their lives. The study findings also highlighted the importance of healthcare professionals undertaking end of life discussions with patients throughout their illness trajectory to ensure people with ESKD are afforded the opportunity to be involved in timely decision making and provided with good quality end of life care.

A inicios del año 2020, se registraron 4,300 asegurados a EsSalud diagnosticados con Enfermedad Renal Crónica Terminal (ERCT) en el departamento de Lima, quienes han venido recibiendo sesiones de hemodiálisis en el Centro Nacional de Salud Renal (CNSR) y clínicas contratadas para este servicio, según lo reportado por la IAFAS antes mencionada. Por parte de los asegurados al SIS, el Fondo Intangible Solidario en Salud (FISSAL) informó que a inicios del 2020 que 6 mil 268 asegurados vienen recibiendo hemodiálisis en centros particulares de salud de Lima Metropolitana y las diferentes regiones del país. El presente proyecto plantea brindar el servicio ambulatorio de hemodiálisis a pacientes con Enfermedad Renal Crónica Terminal afiliados a la IAFAS EsSalud, puesto que tiene una sobredemanda que requieren del servicio de Hemodiálisis, y que actualmente no se encuentra cubierta ni por la oferta propia ni por la subcontratada con otros centros de hemodiálisis.  Nuestra estrategia es de “Liderazgo en costos”, con una propuesta de valor basada en atención personalizada con un equipo multidisciplinario, altos estándares de calidad y un modelo de gestión centrado en el paciente, según los Términos de Referencia (TDR) requeridos por EsSalud. Desde el punto de vista financiero, la inversión total del proyecto es de S/. 447,110.00 presentando un VAN de S/. 2,676,707.15 y un TIR es 86.1%. Los principales riesgos del proyecto son los financieros y económicos, como la falta de liquidez y lograr la contratación por la IAFAS EsSalud.
At the beginning of 2020, 4,300 insured persons were registered with EsSalud diagnosed with Terminal Chronic Kidney Disease (ESRD) in the department of Lima, who have been receiving hemodialysis sessions at the National Renal Health Center (CNSR) and clinics hired for this service, as reported by the aforementioned IAFAS. On the part of those insured to the SIS, the Intangible Solidarity in Health Fund (FISSAL) reported that at the beginning of 2020, 6,268 insured have been receiving hemodialysis in private health centers in Metropolitan Lima and the different regions of the country. This project proposes to provide the outpatient hemodialysis service to patients with Terminal Chronic Kidney Disease affiliated to IAFAS EsSalud, since it has an over-demand for them that require the Hemodialysis service, and which is currently not covered even by its own offer nor by the one subcontracted to other hemodialysis centers. Our strategy is “Cost Leadership”, with a value proposition based on personalized attention with a multidisciplinary team, high quality standards and a patient-centered management model, according to the Terms of Reference (TOR) required by EsSalud. From a financial point of view, the total investment of the project is S /. 447,110.00 presenting a NPV of S /. 2,676,707.15 and an IRR is 86.1%. The main risks of the project are financial and economic, such as lack of liquidity and being hired by IAFAS EsSalud
Trabajo de investigación

PhD
Introduction Kidney transplantation confers both survival and quality of life advantages over dialysis for most people with end-stage kidney disease (ESKD). The mortality rate on dialysis is 10-15% per year, compared with 2-4% per year post-transplantation. Short-term graft survival is related to control of the acute rejection process, requiring on-going immunosuppression. Most current immunosuppressive algorithms include one of the calcineurin inhibitors (CNI: cyclosporin or tacrolimus), an anti-metabolite (azathioprine or mycophenolate) and corticosteroids, with or without antibody induction agents (Ab) given briefly peri-transplantation. Despite this approach, between 15-35% of recipients undergo treatment for an episode of acute rejection (AR) within one year of transplantation. Transplantation is not without risk, and relative mortality rates for kidney recipients after the first post-transplant year remain 4-6 times that of the general population. Longer-term transplant and recipient survival are related to control of chronic allograft nephropathy (rooted in the interplay of AR, non-immunological factors, and the chronic nephrotoxicity of CNI) and limitation of the complications of chronic ESKD and long-term immunosuppression: cardiovascular disease, cancer and infection, which are responsible for 22%, 39% and 21% of deaths respectively. This thesis is presented as published works on the theme of immunosuppression and cancer after kidney transplantation. The work presented in the first chapters of this thesis has striven to identify, evaluate, synthesise and distil the entirety of evidence available of new and established immunosuppressive drug agents through systematic review of randomised trial data, with particular emphasis on quantifying harms of treatment. The final chapters use inception cohort data from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), which is first validated then used to explore the risk of cancer in more detail than was possible from trial data alone. Interleukin 2 receptor antagonists Interleukin-2 receptor antagonists (IL2Ra, commercially available as basiliximab and daclizumab) are humanised or chimeric IgG monoclonal antibodies to the alpha subunit of the IL2 receptor present only on activated T lymphocytes, and the rationale for their use has been as induction agents peri-transplantation. Introduced in the mid-1990s, IL2Ra use has increased globally, and by 2003 38% of new kidney transplant recipients in the United States and 25% in Australasia received an IL2Ra. This study aimed to systematically identify and synthesise the evidence of effects of IL2Ra as an addition to standard therapy, or as an alternative to other induction agents. We identified 117 reports from 38 randomised trials involving 4893 participants. Where IL2Ra were compared with placebo (17 trials; 2786 patients), graft loss was not different at one (Relative Risk -RR 0.84; 0.64 to 1.10) or 3 years (RR 1.08; 0.71 to1.64). AR was reduced at 6 months (RR 0.66; 0.59 to 0.74) and at 1 year (RR 0.66; 0.59 to 0.74) but cytomegalovirus (CMV) disease (RR 0.82; CI 0.65 to 1.03) and malignancy (RR 0.67; 0.33 to1.36) were not different. Where IL2Ra were compared with other antibody therapy no significant differences in treatment effects were demonstrated, but IL2Ra had significantly fewer side effects. Given a 40% risk of rejection, 7 patients would need treatment with IL2Ra in addition to standard therapy, to prevent 1 patient having rejection, with no definite improvement in graft or patient survival. There was no apparent difference between basiliximab and daclizumab. Tacrolimus versus cyclosporin for primary immunosuppression There are pronounced global differences in CNI use; 63% of new kidney transplant recipients in the USA but only 22% in Australia receive tacrolimus as part of the initial immunosuppressive regimen. The side effects of CNI differ: tacrolimus is associated more with diabetes and neurotoxicity, but less with hypertension and dyslipidaemia than cyclosporin, with uncertainty about equivalence of nephrotoxicity or how these relate to patient and graft survival, or impact on patient compliance and quality of life. This study aimed to systematically review and synthesise the positive and negative effects of tacrolimus and cyclosporin as initial therapy for renal transplant recipients. We identified 123 reports from 30 randomised trials involving 4102 participants. At 6 months graft loss was reduced in tacrolimus-treated recipients (RR 0•56; 0•36 to 0•86), and this effect persisted for 3 years. The relative reduction in graft loss with tacrolimus diminished with higher levels of tacrolimus (P=0.04), but did not vary with cyclosporin formulation (P=0.97) or cyclosporin level (P=0.38). At 1 year, tacrolimus patients suffered less AR (RR 0•69; 0•60 to 0•79), and less steroid-resistant AR (RR 0•49; 0•37 to 0•64), but more insulin-requiring diabetes (RR 1•86; 1•11 to 3•09), tremor, headache, diarrhoea, dyspepsia and vomiting. The relative excess in diabetes increased with higher levels of tacrolimus (P=0.003). Cyclosporin-treated recipients experienced significantly more constipation and cosmetic side-effects. We demonstrated no differences in infection or malignancy. Treating 100 recipients with tacrolimus instead of cyclosporin for the 1st year post-transplantation avoids 12 suffering acute rejection and 2 losing their graft but causes an extra 5 to become insulin dependent diabetics, thus optimal drug choice may vary among patients. Target of rapamycin inhibitors for primary immunosuppression Target of rapamycin inhibitors (TOR-I) are among the newest immunosuppressive agents and have a novel mode of action but uncertain clinical role. Sirolimus is a macrocyclic lactone antibiotic and everolimus is a derivative of sirolimus. Both prevent DNA synthesis resulting in arrest of the cell cycle. Animal models suggested TOR-I would provide synergistic immunosuppression when combined with CNI, but early clinical studies demonstrated synergistic nephrotoxicity. Since then diverse trials have explored strategies that avoid this interaction and investigated other potential benefits. The aim of this study was to systematically identify and synthesise available evidence of sirolimus and everolimus when used in initial immunosuppressive regimens for kidney recipients. We identified 142 reports from 33 randomised trials involving 7114 participants, with TOR-I evaluated in four different primary immunosuppressive algorithms: as replacement for CNI, as replacement for antimetabolites, in combination with CNI at low and high dose, and with variable dose of CNI. When TOR-I replaced CNI (8 trials, 750 participants), there was no difference in AR (RR 1.03; 0.74 to 1.44), but creatinine was lower (WMD -18.31 umol/l; -30.96 to -5.67), and bone marrow more suppressed (leucopoenia RR 2.02; 1.12 to 3.66, thrombocytopenia RR 6.97; 2.97 to 16.36, anaemia RR 1.67; 1.27 to 2.20). When TOR-I replaced antimetabolites (11 trials, 3966 participants), AR and CMV were reduced (RR 0.84; 0.71 to 0.99 and RR 0.49; 0.37 to 0.65) but hypercholesterolaemia was increased (RR 1.65; 1.32 to 2.06). When low was compared to high-dose TOR-I, with equal CNI dose (10 trials, 3175 participants), AR was increased (RR 1.23; 1.06 to 1.43) but GFR higher (WMD 4.27 ml/min; 1.12 to 7.41). When low-dose TOR-I and standard-dose CNI were compared to higher-dose TOR-I and reduced CNI AR was reduced (RR 0.67; 0.52 to 0.88), but GFR also reduced (WMD -9.46 ml/min; -12.16 to -6.76). There was no significant difference in mortality, graft loss or malignancy risk demonstrated for TOR-I in any comparison. Generally surrogate endpoints for graft survival favoured TOR-I (lower risk of acute rejection and higher GFR) and surrogate endpoints for patient outcomes were worsened by TOR-I (bone marrow suppression, lipid disturbance). Long-term hard-endpoint data from methodologically robust randomised trials are still needed. Monoclonal and polyclonal antibody therapy for treating acute rejection Strategies for treating AR include pulsed steroids, an antibody (Ab) preparation, the alteration of background immunosuppression, or combinations of these options. In 2002, in the USA 61.4% of patients with AR received steroids, 20.4% received Ab and 18.2% received both. The Ab available for AR are not new: horse and rabbit derived polyclonal antibodies (ATG and ALG) have been used for 35 years, and a mouse monoclonal antibody (muromonab-CD3) became available in the late 1980s. These preparations remove the functional T-cell population from circulation, producing powerful saturation immunosuppression which is useful for AR but which may be complicated by immediate toxicity and higher rates of infection and malignancy. The aim of this study was to systematically evaluate and synthesise all evidence available to clinicians for treating AR in kidney recipients. We identified 49 reports from 21 randomised trials involving 1394 participants. Outcome measures were inconsistent and incompletely defined across trials. Fourteen trials (965 patients) compared therapies for 1st AR episodes (8 Ab versus steroid, 2 Ab versus another Ab, 4 other comparisons). In treating first rejection, Ab was better than steroid in reversing AR (RR 0.57; CI 0.38 to 0.87) and preventing graft loss (RR 0.74; CI 0.58 to 0.95) but there was no difference in preventing subsequent rejection (RR 0.67; CI 0.43 to 1.04) or death (RR 1.16; CI 0.57 to 2.33) at 1 year. Seven trials (422 patients) investigated Ab treatment of steroid-resistant rejection (4 Ab vs another Ab, 1 different doses Ab, 1 different formulation Ab, 2 other comparisons). There was no benefit of muromonab-CD3 over ATG or ALG in reversing rejection (RR 1.32; CI 0.33 to 5.28), preventing subsequent rejection (RR 0.99; CI 0.61 to 1.59), graft loss (RR 1.80; CI 0.29 to 11.23) or death (RR 0.39; CI 0.09 to 1.65). Given the clinical problem caused by AR, comparable data are sparse, and clinically important differences in outcomes between widely used interventions have not been excluded. Standardised reproducible outcome criteria are needed. Validity of cancer data in an end stage kidney disease registry Registries vary in whether the data they collect are given voluntarily or as a requirement of law, the completeness of population coverage, the breadth of data collected and whether data are assembled directly or indirectly through linkage to other databases. Data quality is crucial but difficult to measure objectively. Formal audit of ANZDATA cancer records has not previously taken place. The aim of this study was to assess agreement of records of incident cancer diagnoses held in ANZDATA (voluntary reporting system) with those reported under statute to the New South Wales (NSW) state Central Cancer Registry (CCR), to explore the strengths and weaknesses of both reporting systems, and to measure the impact of any disagreement on results of cancer analyses. From 1980-2001, 9453 residents received dialysis or transplantation in NSW. Records from ANZDATA registrants were linked to CCR using probabilistic matching and agreement between registries for patients with 1 or more cancers, all cancers and site-specific cancer was estimated using the kappa-statistic (κ). ANZDATA recorded 867 cancers in 779 (8.2%) registrants; CCR 867 cancers in 788 (8.3%), with κ =0.76. ANZDATA had sensitivity 77.3% (CI 74.2 to 80.2), specificity 98.1% (CI 97.7 to 98.3) if CCR records were regarded as the reference standard. Agreement was similar for diagnoses whilst receiving dialysis (κ =0.78) or after transplantation (κ =0.79), but varied by cancer type. Melanoma (κ =0.61) and myeloma (κ =0.47) were less good; lymphoma (κ =0.80), leukaemia (κ =0.86) and breast cancer (κ =0.85) were very good. Artefact accounted for 20.8% non-concordance but error and misclassification did occur in both registries. Cancer risk did not differ in any important way whether estimated using ANZDATA or CCR records. Quality of cancer records in ANZDATA are high, differences largely explicable, and seem unlikely to alter results of analyses. Risk of cancer after kidney transplantation Existing data on the magnitude of excess risk of cancer across different kidney recipient groups are sparse. Quantifying an individual transplant candidate’s cancer risk informs both pre-transplant counselling, treatment decisions and has implications for monitoring, screening and follow-up after transplantation. The aims of this study were firstly to establish the risk of cancer in the post-transplant population compared to that experienced by the general population, and secondly to quantify how excess risk varied within the transplanted population, seeking to establish meaningful absolute risk estimates for post-transplant cancer based on unalterable recipient characteristics known a priori at the time of transplantation. 15,183 residents of Australia and New Zealand had a transplant between 1963 and 2004, and were followed for a median of 7.2 years (130,186 person-years), with 1642 (10.8%) developing cancer. Overall, kidney recipients had 3 times the cancer risk, with risk inversely related to age (Standardised Incidence Ratio of 15 to 30 in children reducing to 2 in people > 65 years). Female recipients aged 25 -29 had rates of cancer (779.2/100,000) equivalent to women aged 55 - 59 from the general population. The risk pattern of lymphoma, colorectal and breast cancer was similar to the overall age trend, melanoma showed less variability across ages and prostate cancer showed no risk increase. Within the transplanted population cancer risk was affected by age differently for each sex (P=0.007), and was elevated for recipients with prior non-skin malignancy (Hazard Ratio: HR 1.40; 1.03 to 1.89), of white race (HR 1.36; 1.12 to 1.89), but reduced for those with diabetic ESKD (HR 0.67; 0.50 to 0.89) Rates of cancer in kidney recipients were similar to non-transplanted people 20 -30 years older, but risk differed across patient groups. Men aged 45 - 54 at transplantation with graft function at 10 years had a risk of cancer that varied from 1 in 13 (non-white, diabetic ESKD, no prior cancer) to 1 in 5 (white, prior cancer, ESKD from other causes).

Thesis (Ph. D.)--University of Sydney, 2006.
Title from title screen (viewed 21 May 2007). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Public Health, Faculty of Medicine. Includes bibliographical references. Also available in print form.

A national study was devised to define, using prospective methods, the Scottish renal replacement therapy (RRT) population in terms of numbers, social circumstances, age, mode of presentation for RRT, aetiology of renal failure, comorbid illness, mode of RRT, hospitalisation, mortality and quality of life. The attainment of the recommended treatment standards (UK Renal Association) and their impact along with the factors listed above, upon patient outcomes was assessed. Care by a nephrologist prior to RRT increased the likelihood of a patient having definitive vascular access and attaining the haemoglobin standard, and decreased the time spent in hospital in the first year of RRT. The recommended percentage of patients did not attain haemoglobin, adequacy, albumin or other serum biochemistry standards throughout the first 18 months of RRT. The use of erythropoietin was fundamental to attaining recommended haemoglobin levels. Attaining the haemoglobin standard reduced the risk of death over two years and had beneficial influence upon the number of days spent in hospital. The presence of a fistula (or graft) was the most important factor positively influencing urea reduction ratio (URR). Increasing URR was shown to confer a survival benefit over 2 years in the group treated purely by haemodialysis and reduced time spent in hospital during the first year of treatment. A large demand upon in-patient services was demonstrated. Increased patient cormorbidity and age adversely affected frequency of hospitalisation and total time in hospital in the first year of treatment. Mortality is high amongst patients starting RRT. One year survival was 72.5% (84.2% excluding deaths in the first 90 days), two year survival was 58.5% (68% excluding 90 day deaths). 14% of the cohort died within the first 90 days of RRT. Comorbidity, age, serum albumin and attained haemoglobin significantly affected survival. This study expands the available evidence upon which to base future refinements to clinical practice and recommended standards of care. It provides vital data upon which to base future RRT service planning and research.

This thesis assessed cognitive impairment in people with end stage kidney disease. It found that over a third were cognitively impaired. More than half of those who had not yet started kidney replacement treatment and those already receiving haemodialysis were more likely than other groups to be cognitively impaired. The implications from these findings will influence people being able to make informed decisions about their healthcare, and that changes for patient education ought to occur due to altered levels of understanding.

Background: The extent and the distribution of end stage kidney disease (ESKD) in Libya have not been reported despite provision of dialysis over 4 decades. The aim of this thesis is to develop the first comprehensive description of the epidemiology of dialysis-treated ESKD in adults in Libya as well as to assess the outcomes of this treatment. Methods: A structured interview regarding dialysis provision and infection control measures was conducted with the medical directors of all 40 dialysis centres and 28 centres were visited. In the same time demographic and clinical data were obtained regarding all adult patients treated at all maintenance dialysis facilities in Libya from May to August 2009. Additional information about the patterns of vascular access used for haemodialysis (HD) as well as prevalence and incidence of hepatitis Band/or C infection was collected and analysed. Subsequently data were collected prospectively from September 2009 to August 2010. Results: There were 40 functioning maintenance dialysis centres in Libya (one of them was serving children only). The total number of adult patients was 2417. The prevalence rate of ESKD treated by dialysis was 624 per million population. Most dialysis units were located in the northern part of the country and only 12.5% were free standing units. Only three centres offered peritoneal dialysis. There were 192 HD rooms. They hosted 713 functioning HD stations, giving a ratio of one machine to 3.4 patients. Nephrologist/internist to patient ratio was 1:40 and nurse to patient ratio was 1:3.7. There was wide variation in monitoring of dialysis patients with dialysis adequacy assessed only in a minority. 85% of prevalent patients were aged <65 years and 58% were male. The prevalence of ESKD varied considerably with age with a peak at 55-64 years (2475 pmp for males; 2197 pmp for females). The annual incidence rate was 282 pmp with some regional variation and a substantially higher rate in the South (617 pmp). The most common cause of ESKD among prevalent and incident patients was diabetes. Other important causes were glomerulonephritis, hypertensive nephropathy and congenital or hereditary diseases. During one year follow- up, 458 deaths occurred, (crude annual mortality rate of 21.2%). Of these, 3 1 % were due to ischaemic heart disease, 16% cerebrovascular accidents and 16% due to infection. Annual mortality rate was 0-70% in different dialysis centres. Best survival was in age group 25-34 years. Binary logistic regression analysis identified age at onset of dialysis, physical dependency, diabetes and predialysis urea as independent determinants of increased mortality. Of all dialysis- treated patients, 34.9% were sero-positive for HBV and/or HCV (anti-HCV positive 31.1%; HBsAg positive 2.6%; both positive \.2%). The prevalence of HBV±HCV infection varied widely between HD centres from 0% to 75.9%. Sero-positive patients were younger, had longer time on dialysis and more previous blood transfusions. Prospective follow-up revealed an incidence ofsero-conversion of7.7% during 1 year (7.1% HCV; 0.6% HBV). Wide variation in rates of newly acquired infections was observed between dialysis centres. Duration of dialysis, history of previous renal transplant and history of receiving HD in another centre in Libya were significantly associated with sero-conversion. The majority of HD- treated patients (91.9%; n=1573) were using permanent vascular access in the form of arteriovenous fistula or arteriovenous graft. Patients with permanent vascular access were more likely to be male and less likely to be diabetic. Most patients had commenced HD using a temporary central venous catheter (91.8%). Vascular access- related complications were: thrombosis (46.7%), aneurysm (22.6%), infection (11.5%) and haemorrhage (10.2%). Hospitalisation for VA related complications was reported by 31.4%. Conclusion: ESKD in Libya is a major health problem where the incidence rate is among the highest in the world. Despite rapid expansion of dialysis services throughout the country, this thesis has identified that many aspects of dialysis provision are suboptimal and that outcomes are relatively poor. We have identified several major challenges to improving the quality of dialysis provision including lack of dialysis practice guidelines, absence of auditing and quality control and limited access to kidney transplantation. As Libya reorganises its health services in the post-conflict period it is hoped that this study will be the first step in establishing a renal registry and that the areas of concern highlighted will prompt the implementation of national clinical practice guidelines for dialysis.

Faible masse musculaire a été peu étudiée chez les patients avant le stade terminal de la maladie rénale chronique (MRC). Nous avons évalué la masse musculaire à partir de la créatininurie des 24h pour étudier ses déterminants, son évolution avec le déclin de la fonction rénale ainsi que ses liens avec les risques de progression vers l’insuffisance rénale terminale traitée (IRTT) et de décès avant IRTT. Dans la cohorte NephroTest incluant 1429 patients avec une MRC stades 1 à 4, le débit de filtration glomérulaire a été mesuré par la clairance du 51Cr-EDTA (DFGm) et estimé par l’équation CKD EPI (DFGe). La créatininurie moyenne à l’inclusion diminuait de 15.3±3.1 à 12.1±3.3 mmol/24 chez les hommes et de 9.6±1.9 à 7.6±2.5 chez les femmes, pour une baisse du DFGm de ≥ 60 à < 15 mL/min/1.73 m2. Être plus âgé, avoir un diabète, un faible IMC ou un niveau faible de protéinurie et d’apports protidiques était associé à un niveau faible de créatininurie. Un déclin annuel du DFGm de 5 mL/min/1.73 m2 était lié à une baisse de créatininurie, indépendamment de ces déterminants. Au cours d’un suivi médian de 3.6 ans, 229 patients ont développé une IRTT, et 113 sont décédés avant IRTT. Après ajustement sur les facteurs de confusion, le hasard ratio (HR) était de 1.6 (0.88-2.9) pour le risque de décès et de 0.60 (0.39-0.91) pour le risque d’IRTT, dans le 1er vs 4ème quartile de créatininurie. La baisse de la créatininurie apparait précocement dans la MRC et est liée au décès avant dialyse. La diminution du risque d’IRTT pourrait s’expliquer par un démarrage plus tardif de la dialyse en raison d’une surestimation du DFGm par le DFGe chez les patients avec une faible créatininurie
Mainly described in patients on dialysis, muscle wasting has received little attention in early stage chronic kidney disease (CKD). We used 24-hour creatininuria to assess determinants of low muscle mass and its putative associations with CKD outcomes, using data from the NephroTest cohort, including 1429 non-dialysis patients with CKD stages 1 to 5. Kidney function was assessed with both measured (mGFR, by 51Cr-EDTA renal clearance) and estimated glomerular filtration rate (eGFR, by CKD-EPI equation). End-stage renal disease (ESRD) and pre-ESRD death were the main studied outcomes. The mean baseline creatininuria decreased from 15.3±3.1 to 12.1±3.3 mmol/24 h in men and from 9.6±1.9 to 7.6±2.5 in women, when mGFR fell from ≥ 60 to < 15 mL/min/1.73 m2. Other determinants of low creatininuria were an older age, diabetes, a lower body mass index, a lower level of proteinuria or protein intake. A fast annual decline in mGFR of 5 mL/min/1.73 m2 was linked with a 2-fold decrease in creatininuria, independent of changes in protein intake and other determinants of muscle mass. Over a median follow-up of 3.6 years, 229 patients developed ESRD and 113 patients died before ESRD. After adjustment for confounders, patients with low muscle mass showed a significantly higher risk for pre-ESRD death (HR 1.6, 95% CI 0.88-2.9), but a lower risk for ESRD (HR 0.60, 95% CI 0.39-0.91). The latter was reversed (HR 1.5, 95% CI 1.01-2.4) when mGFR was replaced by eGFR. Decrease in 24-hour creatininuria may appear early in CKD patients, is related to pre-ESRD death. The lower risk for ESRD may reflect later dialysis start due to overestimation of true GFR by eGFR in patients with low muscle mass

Depression is common in haemodialysis (HD) patients and is often unrecognised and undertreated, though associated with excess morbidity and mortality. Diagnosis is challenging due to symptom overlap with kidney failure, with fatigue being the most common overlapping symptom. Research on the effectiveness of antidepressant medication in this setting is sparse. A recent systematic review advocated well-designed Randomised Controlled Trials (RCTs) in this setting. The studies reported in this thesis had a number of aims. The main aim was to undertake a multicentre feasibility randomised, double blind, placebo-controlled trial of sertraline in patients on HD with Major Depressive Disorder (MDD). To identify suitable patients for this, a screening phase was required, which also allowed determination of the prevalence of depression in this setting and of the relative effectiveness of screening tools Patient Health Questionnaire-2 (PHQ-2), Patient Health Questionnaire-9 (PHQ-9), and Beck Depression Inventory-II (BDI-II). It also allowed examination of the relationships of fatigue in this setting (assessed mainly by the Multidimensional Fatigue Inventory (MFI), including those with a diagnosis, and management of depression. The finding, during screening, that a large proportion of the HD cohort was already on antidepressant treatment, presented the opportunity to study 'real-life' practice patterns in the management of antidepressant treatment in this setting. Recruitment into the RCT was difficult. 1,355 patients in five HD centres were considered for screening, but 243 of these were excluded, mainly because of their inability to read and understand English. Of the remaining 1,110 patients, 709 consented to screening. 231 of these screened positive for high depression symptoms but 130 were not considered for the trial phase, mainly because of concurrent treatment for depression (68 patients), and other contraindicated conditions and medication. In addition, 38 patients declined to take part in the psychiatric interview necessary for diagnosis of MDD. Of the 63 who underwent the diagnostic interview, 37 (58.7%) were diagnosed with MDD and 30 consented to enter the RCT and were randomised into sertraline or placebo groups. This was half of the anticipated recruitment into the RCT. Twenty-one patients (70%) completed the six-month study, eight of 15 in the sertraline group and 13 of 15 in the placebo group (p < 0.05). Drop out was mainly due to adverse or serious adverse events. Depression scores (BDI-II and Montgomery-Åsberg Depression Rating Scale (MADRS)) improved significantly in both the sertraline and placebo groups over six months but there were no significant differences between the treatment groups. There was a slight suggestion of more rapid improvement over the first two months on sertraline, but this was not significant. Fatigue scores were high in all sub-domains - with only a weak relationship with age and comorbidity. Mental fatigue was the strongest independent predictor of high depressive symptoms (BDI-II ≥16, PHQ-9 ≥8), while physical fatigue had the strongest relationship with dialysis recovery time, and survival. Distinguishing between these components of fatigue may have a role in refining the diagnosis and management of MDD. Forty-one of the 76 patients on antidepressant medication at screening were followed up for a mean of 14±5 months. Ten different antidepressant agents were being taken - the most common being Citalopram (39%). Most had been prescribed by GPs. Two-thirds of patients either deteriorated or failed to improve in terms of BDI-II scores during follow-up, many of whom had had no adjustment of medication during this time. Diagnostic evaluation at follow-up showed 37% to be suffering from current or recurrent major depressive episodes (MDE), 48% to have evidence of past MDE, and 15% to have no evidence of ever having been depressed. These empirical studies confirm that depression is very common in HD patients. Its diagnosis is complicated due to symptom overlap with the uraemic syndrome. Fatigue seems to be a key area of overlap with symptoms of depression with a complex relationship. There was no obvious benefit from antidepressants in this feasibility RCT and there was a high drop-out rate due to adverse events, particularly in the sertraline group. These findings raise concerns about the benefits and risks of antidepressants in patients on HD. Current practice patterns may be subjecting patients to substantial risk for little or no benefit. Identifying whether antidepressant medication is effective in this context is a major clinical need, hence the requirement for a definitive study. There is no doubt that to undertake a definitive study would pose considerable recruitment challenges. The findings presented here emphasise the importance of finding ways to overcome these challenges that might include efforts to incorporate patients already taking antidepressants.

The worldwide population of patients with chronic kidney disease (CKD) is growing, with estimated prevalence at 12-15% of adults. Of particular concern are those with late stage CKD, defined as an estimated glomerular filtration rate (eGFR)of less than 30 ml/min/1.73m2, as they are susceptible to the highest risk of adverse outcomes such as progression to end stage kidney disease (ESKD), cardiovascular disease and all-cause mortality (1, 2). As such, late stage CKD patients are often managed in specialized clinics with set clinical targets, standardized education and multi-disciplinary care(3). A key clinical target for therapeutic intervention and prevention of the progression of CKD is blood pressure (BP) reduction(4). Yet, multiple relevant questions remain regarding the strength and nature of association of BP with clinical outcomes in late stage CKD. As the risks of hypotension-related complications are high in late stage CKD, it remains unclear whether strict BP control delays CKD progression in a real world clinic population(5). Furthermore, it is unclear how to appropriately specify the nature of the longitudinal association between BP and clinical outcomes of ESKD and mortality. The overall objective of this thesis is to examine the longitudinal association of BP and adverse clinical outcomes in a cohort of 1203 patients (mean eGFR 17.8 ml/min/1.73m2; mean of 6.7 BP measures per patient) with late stage CKD. In our first paper we examined the association of repeat measures of BP with CKD progression, defined as a decline in eGFR. When modeling eGFR using longitudinal linear regression, we found that its over-time trajectory was non-linear and that this trajectory was modified by BP; thus, we found a significant time-dependant association between BP and eGFR. When modeling time to eGFR decline ≥ 30% using Cox proportional hazards regression with categorized BP specified as a time-dependent exposure, BP was significantly associated with risk of eGFR decline; in particular, extremes of low and high systolic blood pressure (SBP) and high diastolic blood pressure (DBP) significantly increased the risk of eGFR decline. In our second paper, we examined different methods of modelling longitudinal BP and its association with time to mortality and ESKD. We found that elevations in SBP and DBP, in particular, when expressed as current (most recent visit), lag (previous visit), and cumulative exposure were significantly associated with increased risk of ESKD while low SBP (current, lag and cumulative exposure) was significantly associated with increased risk of mortality. Baseline BP measures were not statistically significantly associated with any outcomes. In patients with more moderate ranges of SBP (121-140) or DBP (60-85) at baseline, a subsequent rise to >160 or > 85 respectively, was associated with an increased risk of ESKD. Thus, longitudinal BP measures in late-stage CKD are significantly associated with adverse outcomes and convey important information beyond baseline BP measures.

The aim of the study was to evaluate the effects of patient education on measures of compliance amongst patients with End Stage Renal Disease (ESRD) on haemodialysis. The patients included in the study were receiving haemodialysis at the time of recruitment. The primary measure of compliance was interdialytic fluid gain; the data was collected from the patients‟ dialysis records on a monthly basis. Prior to the education program a Kidney Disease Questionnaire (KDQ) was administered to assess baseline knowledge. The percentage change in knowledge score after the education program was also recorded, with any change in knowledge score correlated to any change in compliance behaviours. After providing written consent, study participants (n=51) were randomised to either the intervention (education) group n=26 or control group n=25. The intervention group were participants in a newly developed structured education program conducted over a four - week period. The control group received their normal standard therapy, which included ad hoc education from the nurses in their haemodialysis unit. Compliance in the study group appeared to be affected by gender, and Aboriginality appeared to have a direct influence on compliance. Using the measures of compliance, fluid gains improved by 42% with a 75% improvement in knowledge in the intervention group compared to a 19% improvement in fluid gains in the control group with a 52% improvement in knowledge. Whilst there was some improvement in attendance (missed dialysis) following the education program, a noted trend was all the patients who were non-compliant with attendance were Aboriginal. Whilst the sample was small the results were encouraging; the effect of education on compliance in the ESRD patient was shown in the clinical outcomes as being associated with an improvement in the principal outcome measure of interdialytic session fluid gain. However, the findings also suggest a structured program design may not meet the needs of many of the patients who receive dialysis. Treatment programs need to be designed to encompass the needs of all patient groups with an emphasis on self management, in order to provide adequate health care and maximise clinical outcomes. Recommendations have been made with regard to a more structured, directed approach to patient education programs. Aboriginal patients clearly had the greatest problem with compliance, as did the younger age groups and males. Any future educational program should address social, financial and physical benefit to patients and their care givers which in the longer term will provide cost savings and ultimately improved patient well being. This project demonstrated the usefulness of a formal education program in assisting the majority of participants to improve their knowledge and in some improve their compliance with fluid management and other aspects of ESRD management.

Thesis (M.S.)--University of Toledo, 2006.
"In partial fulfillment of the requirements for the degree of Master of Science in Nursing." Major advisor: Jane C. Evans. Includes abstract. Document formatted into pages: v, 53 p. Title from title page of PDF document. Bibliography: pages 42-43.

The thesis that this dissertation aims to defend is: Certain self-management behaviours in End Stage Renal Disease are predicted by self-efficacy, patient activation, and psychological distress, and in turn predict clinical status. However, self-management is often oversimplified and poorly operationalised, in both the literature and in clinical practice, to adherence and 'good/bad' distinctions that may impede future investigations and interventions. End Stage Renal Disease (ESRD) is a chronic condition associated with significant morbidity and increased risk of death. It is commonly treated with haemodialysis, a life sustaining treatment that last approximately four hours, repeated in a healthcare centre or at home, at least three times a week. ESRD also necessitates adherence to a complex set of dietary and fluid intake guidelines, in addition to a complex medication regimen, if the person is to avoid a further increase in the risk of severe symptoms and death. Chronic illness self-management is more than just adherence to prescribed medical treatments however, and requires an individual to preserve their emotional wellbeing, maintain social support networks, and continue to function in a variety of social roles and situations. While this has long been recognised in the theoretical literature about self-management, these concepts are often not well translated into clinical practice or empirical investigations of self-management behaviour in ESRD. When operationalising self-management, some investigations treat the 'behaviour' element of self-management as being limited to dialysis, medication, and fluid adherence, or are ignored in favour of psychological correlates such as self-efficacy. A frequent criticism of the self-management literature is that self-efficacy is often treated as an outcome, rather than a psychological component of changes in behaviour, wellbeing, or clinical outcomes. The investigations presented in this dissertation seek to investigate self-management in terms of specific behaviours that go beyond adherence. In doing so, they explore two different types of self-management behaviour, here termed 'cooperative' and 'defensive' self-management. These behaviours can then be examined in relation to adherence and self-efficacy, as well as other theoretically related factors including patient activation, psychological distress, and illness perceptions. The first three chapters set out the background to the empirical investigations reported in this dissertation. Chapter one covers the background on ESRD and its treatment. Chapter two describes the current state of the conceptual and empirical literature concerning self-management. Chapter three combines a narrative review of empirical investigations into self-management in ESRD, and a review of publically available resources concerning self-management in ESRD. Chapter four describes the methods used in the following empirical chapters. Chapters five, six, seven and eight report original empirical investigations on self-management in ESRD. Chapter nine is a discussion of the combined findings, and their implications in the wider clinical and academic context. Chapter 5 presents the results of a series of focus groups conducted with people on in-centre haemodialysis for ESRD, and the healthcare professionals involved in their care. These explored what each group understood by 'self-management', the behaviours and tasks that were important, and the practical, social, and emotional facilitators and barriers. A series of interviews conducted with patients eighteen months later revisited these concepts, focusing on motivations for engaging in self-management behaviours. The combined findings revealed that patient and HCP concepts around self-management overlap, but have a different focus, with HCPs seeing self-management as being about adherence, and patients seeing it as a complex balancing act to maintain their health, emotional wellbeing, and social roles. HCPs identified some patients as 'good' and others as 'bad'. Chapter 6 presents the results of a cross-sectional investigation of self-management behaviour and theoretically related psychological factors, including self-efficacy and psychological distress. Self-management was operationalised using an available scale that covered a variety of the behaviours patients and HCPs identified as important in chapter 5, which included both 'cooperative' and 'defensive' subscales. Self-efficacy, patient activation, and psychological distress were related to 'defensive' behaviours, with higher levels of psychological distress being related to the performance of more defensive behaviours. Higher self-efficacy was related to less frequent performance of defensive behaviours. A novel finding was that psychological distress mediated the relationship between self-efficacy and self-management behaviours. The implication that some proactive self-management behaviours may be associated with poorer emotional wellbeing is discussed. Chapter 7 presents the results of an 18 month longitudinal study of self-management behaviour and clinical markers of adherence. It also reports a survival analysis in the same cohort followed up to 30 months. Higher frequency of cooperative self-management behaviours were associated with lower levels of adherence as indicated by clinical markers. This may be due to the dialysis units in which the study took place, and may in fact reflect how self-management support was conducted in the units at the time of the study. Higher self-efficacy was found to be associated with lower mortality over 30 months after controlling for factors such as age and residual kidney function, an original and potentially important finding. The findings in chapters 6 and 7 raised additional questions about how self-management behaviours are measured and what those measurements indicate. To further investigate, and lay the groundwork for a new scale and general guidelines on the operationalisation of self-management in ESRD, a series of cognitive interviews were conducted. These are reported in chapter 8. They were conducted with people on home haemodialysis, a population whose engagement in a whole range of self-management behaviours is likely to be high. The role of social and emotional factors in the scale and behaviours discussed was also explored. The chapter concludes with a series of suggestions for measuring self-management behaviour in ESRD. This dissertation will explore the concept of self-management for people on haemodialysis, the behaviours involved, and their relationship with psychosocial and clinical status.

Background: Chronic kidney disease (CKD) affects approximately 26 million individuals in the United States and is a top priority in the objectives for Healthy People 2020. Despite efforts to improve awareness, discussion of CKD is often minimal or ineffective in the primary care setting. This leads to a lack of patient awareness and knowledge of self-care skills to prevent or slow progression of the disease. A lack of communication of has been attributed to the provider's lack of confidence and knowledge to discuss CKD and to avoid unnecessary stress. Purpose: The purpose of the DNP project is to provide a systematic review of patient-provider communication processes used to influence self-management or behavioral change in primary care and propose a tool to enhance communication and slow progression of CKD. Methods: A systematic review was conducted following the method guidelines of the Cochrane Collaboration. Six electronic databases were searched. Inclusion criteria were adult humans, primary research studies, systematic and literature reviews, focus on communication of self-management or behavioral change strategies, primary outcomes of improving self-management and/or patient outcomes and availability of full-text online or by request. Outcomes: Of the 5765 articles initially identified, 28 studies met inclusion criteria. The studies revealed a lack of evidence directed towards CKD and communication was not directly addressed in a majority of the studies. Interventions most successful in improving patient outcomes were individualized, elicited collaboration or interaction with the patient and provider, were motivational or encouraging and aided in barrier identification and problem solving. A communication tool was developed from the evidence in order to stimulate more meaningful conversation between the patient and provider.

Hyperphosphataemia occurs in end-stage kidney disease and is managed by diet, drinks, drugs, and dialysis. Adherence to the 4Ds is challenging for patients. This thesis reports a pragmatic randomised controlled trial that evaluated the effectiveness of an innovative educational intervention "Taking control of your phosphate with the 4Ds" to improve adherence to phosphate control in adults receiving haemodialysis. The 4Ds, a bundled self-management intervention, was effective in improving patient's confidence about phosphate control methods. Importantly, the intervention was brief and feasible for nurses to deliver during haemodialysis treatment.

Purpose: To evaluate the diagnostic performance of Coronary Computed Tomography Angiography (CCTA) in predicting Myocardial Perfusion Scintigraphy (MPS) perfusion defects in low likelihood patients with End Stage Renal Disease (ESRD) awaiting transplant. Materials and Methods: In total, 131 consecutive patients with ESRD awaiting transplant were prospectively enrolled in this study (86 men; 54±9years). All patients underwent MPS as per standard of care and in addition non-enhanced CT for calcium scoring (CAC score) and Coronary Computed Tomography Angiography (CCTA). Results: The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CAC score in predicting MPS perfusion defects were 88%, 35%, 28% and 92%, respectively. The sensitivity, specificity, PPV and NPV of CCTA in predicting MPS perfusion defects at the patient level were 55%, 87%, 57% and 87%, respectively, and 48%, 92%, 41% and 94% at the vessel level. The diagnostic performance of CCTA in predicting MPS perfusion defects improved when patients with CAC score higher than 1000 (15/70, 21%) were excluded from the analysis. In patients with positive CAC score up to 1000 sensitivity, specificity, PPV and NPV at the patient level were 60%, 93%, 75% and 86% respectively. These were 53%, 91%, 36% and 95%, respectively, at the vessel level. Conclusion: Non-enhanced CT for CAC score and CCTA can be considered useful diagnostic tools in the ESRD population, particularly in identifying patients without coronary artery disease. This approach however had limitations in the presence of high CAC score.

The aim of this study sets out to better understand nephrology nurses’ lived experiences of dying and deaths of patients with ESKD following withdrawal of dialysis. A qualitative research design using an interpretative phenomenological approach was used to explore the experiences of a purposive heterogeneous sample of eight nephrology nurses who were working in private dialysis units. Information was gathered by phenomenological conversations and feed-back sessions. Colaizzi’s phenomenological method was employed to formulate four main themes: 1. Emotional trauma 2. Detachment 3. Loss of altruistic values in nursing 4. being-with-death For the participants in this study, emotional trauma was the most significant. The participants experienced a sense of powerlessness which caused emotions of hopelessness and anger and subsequently a sense of premature mourning and detachment. This state of hopelessness proved to be an obstacle in patient care, resulting in the altruistic values of nursing to be no longer applied. The participants’ ontological confrontation of being-with-death was evident, as they came to terms with the reality of their own death. Recommendations are offered to address the educational aspects of death and dying for nephrology nurses. This study endorses the need for further research into patients with ESKD ‘end-of-life’ which can influence how healthcare professionals should treat these patients during this phase.

Cadmium and lead accumulate in humans and can have toxic effects. Exposure to cadmium is well known to cause kidney damage. Cadmium binds to metallothioneins, proteins that play a role in cadmium transport. Lead exposure’s main effect is on the central nervous system, but associations with kidney disease have also been found, although it is unknown if the latter is a causal association. The main source of both metals within the non-smoking population is from the diet. This thesis aims to 1) compare the biomarkers lead and cadmium concentration in whole-blood, plasma and urine with regard to their ability to discriminate between individuals with different mean concentrations, and to describe the effect of urinary dilution, 2) estimate the association between end-stage renal disease and blood concentrations of cadmium, lead and mercury, using prospectively collected samples for exposure evaluation, 3) use longitudinal data on kidney function makers to evaluate kidney recovery after a substantial decrease in cadmium exposure, and 4) assess the influence of metallothionein polymorphisms (MT1A rs11076161, MT2A rs10636 and MT2A rs28366003) on cadmium-associated kidney toxicity and recovery due to a reduction in Cd exposure. Repeated sampling of whole-blood, plasma and urine was conducted on 48 occupationally lead-exposed men and 20 individuals under normal environmental lead exposure, for estimation of the day-to-day and between individual-variation. Prospective samples were obtained for 118 cases that later in life developed end-stage renal disease, and 378 matched controls. Erythrocyte cadmium, lead, and mercury concentrations were determined and the risk of developing end-stage renal disease associated with metal concentrations was estimated. For evaluation of kidney recovery after a reduction in cadmium exposure and to test for gene-environment interactions, follow-up data on N-acetyl-β‑d-glucosaminidase, β2‑microglobulin, albumin, and gene polymorphisms were obtained for 412 individuals within the Chinese population and the relation to blood and urinary cadmium was assessed. The concentration of lead in blood was found to be the biomarker with the largest fraction of the total variance attributable to between-individual variation, and was therefore the biomarker with the best ability to discriminate between individuals with different mean concentrations, both for individuals under occupational and normal environmental exposure (91 and 95%, respectively). Adjusting for urinary dilution had a great effect on the fraction of the total variance attributable to between-individual variation among individuals with normal lead exposure but only a minor effect among those who were occupationally exposed. Variance analysis showed that blood concentrations were also the best discriminating biomarker for cadmium. Erythrocyte lead was, in a univariate model, associated with an increased risk of developing end-stage renal disease [odds ratio (OR) = 1.54 for an interquartile range increase, with a 95% confidence interval (CI) = 1.18-2.00], while erythrocyte mercury was negatively associated (OR = 0.75 for an interquartile range increase, with a 95% CI = 0.56-0.99). For erythrocyte cadmium, the OR was 1.15 with a 95% CI of 0.99-1.34. Associations with lead and cadmium were only seen among men. In the study on kidney recovery, the proportion of individuals with albumin level above the 95th percentile decreased between baseline and follow up, but no decrease was found for the tubular markers N-acetyl-β‑d-glucosaminidase and β2-microglobulin. Metallothionein polymorphisms modified cadmium-associated effects on N-acetyl-β‑d-glucosaminidase and β2-microglobulin levels but did not modify cadmium-associated change in any of the kidney function markers between baseline and follow up after a substantial decrease in exposure. Blood concentrations of lead and cadmium are the biomarkers with the best ability to discriminate between individuals with different mean concentrations. Adjustment for urinary dilution has great influence on the fraction of the total variance attributed to between individual variation among urine samples with low lead concentrations, but only a small influence on samples with high lead concentrations. This suggests a difference in excretion. The association between end-stage renal disease and low-level lead exposure, as assessed through prospective erythrocyte samples, gives reason for concern, although further studies are needed to determine causality. A cadmium-associated increase in albumin is reversible after a substantial reduction in exposure, but this is not the case for the observed tubular effects. The tubular kidney effects of cadmium might be modified by the MT1A rs11076161 polymorphism.
För att bedöma exponering för kadmium och bly mäts ofta deras koncentrationer i blod eller urin. Dessa studerades i longitudinella data för 48 blyarbetare och 20 individer med normal miljömässig exponering. Blod- och urinprover togs var annan till var tredje månad. Kadmium- och blykoncentrationer mättes sedan i helblod, plasma och urin. Koncentrationer av bly i blod var den biomarkör som hade den största andelen av den totala variationen som kunde förklaras av skillnader mellan individer, och var därför den biomarkör med den bästa förmågan att särskilja på individer med olika medelkoncentration, både för individer med yrkesexponering och normal miljömässig exponering (91 respektive 95% av variansen berodde på vilken individ blodprovet kom ifrån). Justering för urinens utspädning av bly i urin förbättrar oftast urins användbarhet som biomarkör. För bly stämde detta bara hos dem som inte var blyarbetare. Blodkoncentrationer var också den biomarkör med störst andel av den totala variation som kunde förklaras med skillnader mellan individer för kadmium. Kadmium och bly ackumuleras i njure respektive ben och kan ha toxikologiska effekter. Det är välkänt att höga exponeringsnivåer av kadmium orsakar njurskada och även vid lägre exponeringsnivåer har studier funnit samband med markörer för njurfunktion. Exponering för bly påverkar i första hand det centrala nervsystemet. Studier har dock funnit samband mellan koncentrationer av bly i blod och njurens glomerulära filtrationshastighet. Det är oklart både om dessa associationer, vid låga exponeringsnivåer, är viktiga för hälsan och om de verkligen beror på att kadmium och bly orsakar njurskada. För att studera end-stage renal disease användes prospektiva kohorter där personer lämnat blodprov för forskning: Västerbottens interventionsprogram med prover som tagits vid Västerbottens hälsoundersökningar, MONICA-undersökningar i Norr- och Västerbotten, mammografiundersökningarna i Västerbotten och Malmö kost cancer. Sammanlagt ingick över ett hundra tusen individer i dessa kohorter. Med hjälp av det Svenska njurregistret identifierades sedan 118 personer som senare i livet fått end-stage renal disease. Dessa jämfördes med 378 kontroller. För dessa 496 personer tinades blodprovet (närmare bestämt röda blodkroppar) upp och analyserades för kadmium och bly. För att undersöka njurens förmåga till återhämtning studerades tre områden i Kina varav ett tidigare varit kraftigt kadmiumexponerat. Erytrocytkoncentrationer av bly var, utan att ta hänsyn till några andra variabler, associerat med en ökad risk för att utveckla end-stage renal disease (med oddskvoten 1.54 för en interquartile range ökning av erytrocytbly, med ett 95% konfidensintervall 1.18-2.00). Sambanden kvarstod också efter att ha tagit hänsyn till övriga variabler. För erytrocytkadmium var oddskvoten 1.15 med 95% konfidensintervall 0.99-1.34, och sambandet försvagades när hänsyn togs till andra variabler. Associationerna sågs bland män men inte bland kvinnor. Eftersom kadmium vid höga nivåer orsakar njurskada är det också av intresse att studera om påverkan på njuren går över om exponeringen minskas. Totalt följdes 412 individer upp med mätningar av markörer för njurfunktion och kadmiumkoncentrationer i blod och urin. Första undersökningen gjordes 1998, då man just hade slutat äta kadmiumförorenat ris. En andra undersökning gjordes 2006. Andelen individer med avvikande albuminvärde i urin var lägre vid uppföljningen jämfört med vid baslinjen, men ingen minskning sågs för markörer för tubulär förmåga att återta proteiner. Åttioprocent av kadmium i celler är bundet till proteinet metallotheonin, vilket skyddar mot cellskada, men har också en roll i transporten av kadmium från levern till njurarna. En tidigare studie har visat att njurens känslighet för kadmiumexponering var associerad med genetiska skillnader i detta protein. För att studera genetiska associationer studerades de 412 personerna i den kinesiska studien [då också individernas genotyper av metallotheonin-polymorfierna MT1A rs11076161 (G/A), MT2A rs10636 (G/C) och MT2A rs28366003 (A/G) bestämdes]. Genetiken spelade roll för sambandet mellan förmåga att återta proteiner och kadmium men påverkade inte förändring av njurfunktion efter att man slutat äta kadmiumförorenat ris. Kadmium- och blykoncentrationer i blod är de biomarkörer, av koncentrationer i blod, plasma och urin, med den bästa förmågan att skilja på individer med olika medelkoncentrationer. Justering för urinutspädning påverkade andelen av den totala variationen som kunde förklaras av skillnader mellan individer i stor utsträckning för individer med normal miljömässig exponering men inte bland yrkesexponerade, vilket tyder på en skillnad i hur utsöndringen går till. Associationen mellan end-stage renal disease och låg exponering för bly, uppmätta i prospektiva erytrocytprover, ger orsak till oro, men ytterligare studier behövs för att kunna utvärdera om detta är ett kausalt samband. En kadmiumrelaterad skada av den glomerulära filtrationen är reversibel efter en kraftig reducering i exponering, men detta är inte fallet för tubulär skada. De tubulära njureffekterna av kadmiumexponering kan påverkas av metallotheonin-polymorfier.

Thesis (Ph.D. )--University of Tennessee Health Science Center, 2008.
Title from title page screen (viewed on May 16, 2008 ). Research advisor: Mona N. Wicks, PhD. Document formatted into pages (vii, 87 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 63-73).

Relative changes are detectable in the blood of end-stage renal disease (ESRD) patients during hemodialysis (HD) treatment using optical spectroscopy. However, the potential impacts of several confounding factors that could affect the detection of these changes have not been evaluated. The objectives of this thesis were to: 1) investigate how the variations and/or changes in acid-base and oxygen parameters during HD treatment can affect the optical signature of whole blood of ESRD patients, 2) to investigate the effect of heparin on the optical properties of whole blood and its impact on our method. Blood samples were drawn from 23 ESRD patients at 5 time points during a 4 hour HD treatment and sent for blood gas and blood spectroscopy analyses. No significant correlations were found between the changes in the blood transmittance spectra and acid-base and oxygen parameters. This indicates that the perturbations in these parameters due to HD procedures do not confound the detection of changes in the blood transmittance spectra of ESRD patients during HD treatment. Additionally, the effect of heparin in modifying the optical properties of whole blood does not confound the detection of changes in the blood of ESRD patients due to HD treatment using whole blood-based optical spectroscopy. ANOVA revealed significant (P<0.05) measurable changes in the blood transmittance spectra of ESRD patients during HD treatment. Significant spectral differences (P<0.05) were found between ESRD patients. The lack of uniform spectral characteristics across patients is

The objective of the study is to analyze the factors associated with the severity of pruritus in patients with terminal chronic kidney disease undergoing hemodialysis. The methodology used is based on a cross-sectional study in patients receiving hemodialysis at the Centro Nacional de Salud Renal. Severe pruritus was defined as a score on the visual analogue scale greater than or equal to 7, and the strength of association with the possible risk factors was assessed by calculating prevalence ratios. Regarding the results, 264 patients were included, 59.9% were male, with a mean time on hemodialysis of 10.26 ± 7.14 years. 75% experienced pruritus, of this group, 1 in 3 presented severe pruritus. Hyperphosphatemia and the use of antihistamines were associated with a higher prevalence of severe pruritus (RP 1.71, 95% CI 1.09-267 and RP 2.39, 95% CI 1.51-3.75, respectively). The positive serology for Hepatitis C Virus was described as a protective factor for presenting severe pruritus (RP 0.55, 95% CI 0.33 - 0.89). In conclusion, severe uremic pruritus is a frequent problem in patients with chronic terminal kidney disease who have hyperphosphatemia and treatment with antihistamines independently of the time they have been on hemodialysis.
Revisión por pares

The high levels of end-stage renal disease among Indigenous Australians, particularly in remote areas of the country, are a serious public health concern. The magnitude of the problem is reflected in figures from the Australian and New Zealand Transplant and Dialysis Registry that show that Indigenous Australians experience end-stage renal disease at a rate almost 9–10 times higher than other non-Indigenous Australians. A majority of Indigenous Australians have to relocate to receive appropriate renal dialysis treatment. In some Australian states, renal treatment is based on self-care dialysis which allows those Indigenous Australians to be treated back in their community. Evidence clearly shows that reuniting renal patients with community and family improves overall health and well-being for those Indigenous Australians. With the appropriate resources, training, and support, self-care management of renal dialysis treatment is an effective way for Indigenous people with end-stage renal failure to be treated at home. In this context, the study was used to gain insight and further understanding of the impact that end-stage renal disease and renal dialysis treatment has had on the lives of Indigenous community members. The study findings are from 14 individually interviewed people from South East Queensland. Data from the interviews were analysed using a combination of thematic and content analysis. The study methodology was based on qualitative data principles where the Indigenous community members were able to share their experiences and journeys living with end-stage renal disease. Many of the experiences and understanding closely relate to the renal disease pattern and the treatment with other outside influences, such as social, cultural, and environmental influences, all having an equal impact. Each community member’s experience with end-stage renal disease is unique; some manage with family and medical support, while others try to manage independently. From the study, community members who managed their renal dialysis treatment independently were much more aware of their renal health status. The study provides recommendations towards a model of care to improve the health and well-being is based on self-care and self-determination principles.

This study explored multiple aspects of social support from patients, caregivers and healthcare staff’s perspectives in the Vietnamese haemodialysis context. The study identified the interconnection of roles of patients, caregivers and healthcare staff as members of caregiving triad or support network in providing support in haemodialysis. Contextual factors including financial burden and family culture were found to be important factors affecting the provision of social support. This study’s novel contribution could lead to improving the provision of social support for people on haemodialysis which is crucial due to the growing global burden of end stage kidney disease.

La Polykystose Rénale Autosomique Dominante (PKRAD) est une des pathologies héréditaires les plus fréquentes et affecte environ un individu sur 1000. Elle se caractérise par une importante variabilité clinique, notamment dans l’âge de survenue de l’insuffisance rénale terminale. Deux gènes sont en cause : le gène PKD1 situé sur le chromosome 16 (85% des cas) et le gène PKD2 situé sur le chromosome 4 (15% des cas). Les progrès majeurs dans la compréhension des mécanismes moléculaires impliqués ont permis le développement de stratégies thérapeutiques spécifiques, et de nouvelles questions surgissent : quels patients traiter ? Quand débuter les traitements ? La cohorte Genkyst, qui vise à inclure tous les patients suivis pour PKRAD dans la région Grand Ouest, nous a d’abord permis de décrire la variabilité génétique rencontrée dans la PKRAD. Nous avons ensuite démontré l’existence de fortes corrélations génotype-phénotype, en rapportant l’influence sur l’âge de survenue de l’insuffisance rénale terminale non seulement du gène en cause, mais aussi du type de mutation pour le gène PKD1. Enfin, l’analyse des données cliniques et génétiques de 1341 patients nous a permis de développer un algorithme pronostique, baptisé le PROPKD score, permettant de stratifier le risque de progression vers l’insuffisance rénale terminale. Nous espérons que ces travaux participeront à l’individualisation de la prise en charge des patients atteints de PKRAD, ce qui est un enjeu crucial à l’arrivée des nouveaux traitements
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most frequent Mendelian inherited disorders, and affects approximately one individual out of 1000. ADPKD is marked by a high clinical variability, especially regarding age at end-stage renal disease (ESRD). Two genes are identified: PKD1 located on the chromosome 16 (85% of the pedigrees) and PKD2 located on the chromosome 4 (15% of the pedigrees). Substantial progress in understanding the cellular mechanisms underlying ADPKD has triggered the development of targeted therapies, and new questions are arising: which patients should be treated? When should we begin these treatments? Thanks to Genkyst cohort, which aims to include all consenting ADPKD patients from the western part of France, we first described the important allelic variability encountered in ADPKD. Secondly, we demonstrated the important influence of not only the gene involved, but also of PKD1 mutation type. Last, the analysis of clinical and genetic characteristics of 1341 patients from the Genkyst cohort allowed us to develop a prognostic algorithm, named the PROPKD score for predicting renal outcome in ADPKD. Our hope is that these works will participate in the development of individualized medicine in ADPKD, which is crucial in the context of the emerging targeted therapies

La maladie rénale chronique (MRC) affecte environ 10% de la population adulte et est associée à un risque élevé de progression vers l’insuffisance rénale terminale (IRT), d’événements cardiovasculaires et de décès précoce. Des mesures sont recommandées pour prévenir la progression et les complications de la MRC, mais elles sont souvent basées sur un niveau de preuve faible ou sur la seule opinion d’experts. Dans cette thèse, nous avons utilisé des données observationnelles pour évaluer les pratiques cliniques dans deux domaines clés de la MRC : les abords artérioveineux (AV) en hémodialyse et le contrôle de l’hypertension artérielle (HTA) dans la MRC non terminale. Avec le registre national REIN des traitements de suppléance de l'IRT, nous avons montré que seuls 56% des 53 092 patients adultes incidents en hémodialyse de 2005 à 2013 avaient une voie d’abord AV (fistule ou pontage) créée, telle que recommandée, avant le démarrage de la dialyse, dont 16% étaient non fonctionnelles, nécessitant l'utilisation d'un cathéter associé à une sur-mortalité. La conversion en abord AV fonctionnel était associée à un meilleur pronostic, mais concernait dans les trois premières années de dialyse moins de deux patients sur trois ayant démarré sur cathéter. Dans l’étude de cohorte CKD-REIN, chez 1658 patients avec une MRC modérée à sévère, nous avons mis en évidence un moins bon contrôle de l'HTA et des niveaux de pression artérielle systolique plus élevés en lien avec des apports élevés en sodium, mais pas avec des apports faibles en potassium, évalués sur échantillon urinaire ponctuel. Le ratio sodium/potassium urinaire n'était pas plus discriminant que le sodium seul. Enfin, grâce au réseau International Network of Chronic Kidney Disease cohorts (iNET-CKD), qui inclut 17 cohortes sur 4 continents (N=34 602 patients avec un débit de filtration glomérulaire estimé < 60 mL/min/1,73 m2) nous avons mis en lumière le contrôle médiocre de l’HTA en général dans la MRC au regard des recommandations, avec d'importantes variations entre pays (27 à 61% de pression artérielle ≥140/90 mm Hg) expliquées en partie par les caractéristiques des patients et associées à des profils de traitements antihypertenseurs très différents. En conclusion, cette thèse pointe des écarts importants aux recommandations dans la prise en charge de la MRC en vie réelle et des pistes de prévention des complications liées aux abords AV et un meilleur contrôle de l'HTA
Chronic kidney disease (CKD) affects about 10% of the adult population and is associated with high risk of end-stage kidney disease (ESKD), cardiovascular complications, and premature death. Guidelines recommend a number of measures for the prevention of CKD progression and complications, but these recommendations are often based on low evidence or expert opinion. In this thesis, we used observational data to assess clinical practices in two key areas of CKD: arteriovenous (AV) access for hemodialysis, and hypertension control in moderate to severe CKD. Using data from the French REIN registry of renal replacement therapy for ESKD, we showed that only 56% of the 53,092 adult incident patients on hemodialysis from 2005 through 2013 had an AV access (either fistulae or grafts) created at hemodialysis initiation as recommended, of which 16% were nonfunctional, requiring catheter use associated with high mortality risk. Conversion into functional AV access was associated with better outcome, but less than two out of three patients starting hemodialysis with a catheter experienced this conversion within 3 years after dialysis start. In the CKD-REIN cohort study, among 1658 patients with moderate to severe CKD, we found less hypertension control and higher systolic blood pressure to be associated with higher sodium intake assessed from spot urine, but not with lower potassium intake. Spot urinary sodium/potassium ratio did not appear to add value than sodium alone for patient monitoring. Finally, using data from the International Network of Chronic Kidney Disease cohorts (iNET-CKD), including 17 cohort studies over 4 continents (N=34,602 patients with an estimated glomerular filtration rate < 60 mL/min/1.73 m2), we highlighted a global poor hypertension control in CKD with regards to recommendations, with large variations across countries (from 27 to 61% blood pressure ≥140/90 mm Hg). These variations are partly explained by patients’ characteristics, and associated with very different antihypertensive treatment profiles. In conclusion, this thesis points out major gaps between guideline recommendations and CKD management in real life, and provide clues for the prevention of AV access-related complications and better hypertension control

Kidney failure is an important cause of morbidity and mortality, frequently associated with chronic inflammation of glomeruli and immune hypersensitivity reactions. In this study we aimed to determine if there was an association between HLA alleles and end stage kidney diseases. Towards this objective, we analyzed 87 patients with an average age of 51 years and a mean of 4.5 years of hemodialysis. The main clinical diagnosis of kidney failure in this group was hypertension (38%), diabetes (25%) and glomerulopathies (23%). As a control, we utilized the HLA typing data of 17,541 voluntary marrow donors from the Brazilian national registry. HLA typing was determined by SSO kits (One Lambda, Inc.) and flow cytometry (Luminex technology). Our results demonstrated that, when compared to the normal population, there was a significant association of: 1) hypertension with HLA-A*23 (p=0.014), HLA-A*30 (p<0.001) and HLA-B*41 (p=0.016); 2) diabetes with HLA-A*23 (p=0.004), HLA-A*30 (p=0.033), HLA-B*41 (p=0.023), HLA-B*81 (p=0.020), HLADRB 1*1 (p=0.030) and HLA-DRB1*3 (p=0.013); and 3) glomerulopathies with HLA-A*32 (p<0.001), HLA-B*13 (p<0.001), HLA-B*14 (p=0.004), HLA-DRB1*4 (p=0.030), HLADRB 1*11 (p=0.008) and HLA-DRB1*15 (p<0.001). There was an association between allele frequency and protection against kidney disease in the following situations: 1) hypertension with HLA-A*3 and HLA-DRB1*4; 2) diabetes with HLA-DRB1*11; 3) glomerulopathies with HLA-DRB1*1 and HLA-DRB1*13. In conclusion, HLA alleles may be an important marker of prognosis in chronic renal disease.
A insuficiência renal, frequentemente associada com inflamação glomerular crônica e com reações de hipersensibilidade, é importante causa de morbidade e mortalidade. O objetivo deste estudo foi determinar se havia associação entre alelos HLA e doença renal crônica terminal. Foram analisados 87 pacientes com idade média de 51 anos e realizando hemodiálise há, em média, 4,5 anos. Os principais diagnósticos clínicos da insuficiência renal neste grupo foram hipertensão (38%), diabetes (25%) e glomerulopatias (23%). Como controle foram utilizados dados de tipagens de HLA de 17.541 doadores voluntários de medula óssea do registro nacional Brasileiro. A tipagem de HLA foi determinada através de kits SSO (One Lambda, Inc) e citometria de fluxo (tecnologia Luminex). Nossos resultados demonstraram que, quando comparado com a população normal, havia associação significativa de: 1) hipertensão com HLA-A*23 (p=0,014), HLA-A*30 (p<0,001) e HLAB* 41 (p=0,016); 2) diabetes com HLA-A*23 (p=0,004), HLA-A*30 (p=0,033), HLA-B*41 (p=0,023), HLA-B*81 (p=0,020), HLA-DRB1*1 (p=0,030) e HLA-DRB1*3 (p=0,013); 3) glomerulopatias com HLA-A*32 (p<0,001), HLA-B*13 (p<0,001), HLA-B*14 (p=0,004), HLA-DRB1*4 (p=0,030), HLA-DRB1*11 (p=0,008) e HLA-DRB1*15 (p<0,001). Houve associação entre a frequência de alelos e proteção contra doença renal nas seguintes situações: 1) hipertensão com HLA-A*3 e HLA-DRB1*4; 2) diabetes com HLA-DRB1*11; 3) glomerulopatias com HLA-DRB1*1 e HLA-DRB1*13. Conclusão: alelos HLA podem ser importantes marcadores do prognóstico em doença renal crônica.
Doutor em Imunologia e Parasitologia Aplicadas

Les conditions de sécurité sanitaire encadrant les pratiques d'hémodialyse (HD) et d'hémodiafiltration (HDF) n'intègrent pas les risques liés à des micropolluants comme les perturbateurs endocriniens (PE). Les patients dialysés présentent un risque de surexposition au Bisphénol A (BPA), reconnu comme PE, en raison de sa présence dans les dispositifs médicaux utilisés lors de la dialyse et du risque d'accumulation liée à leur état rénal.Nos premiers travaux ont confirmé la présence du BPA dans les dialyseurs et démontré pour la 1ère fois que l'eau utilisée en HD était également une source de contamination importante en BPA, via la production du dialysat. De plus, nous avons mis en évidence dans l'eau de dialyse la présence de dérivés chlorés du BPA (ClxBPA), sous-produits de chloration de l'eau connus pour leur activité œstrogénique supérieure au BPA. Nous avons ensuite montré que l'HDF entrainait un risque d'exposition aux PE plus important que l'HD, via la contamination du liquide de substitution perfusé chez le patient. Ces résultats permettront aux industriels de prendre en compte le risque de contamination à ces PE ainsi qu'aux médecins et pharmaciens impliqués dans la prise en charge des patients dialysés.Peu de données sont disponibles concernant l'impact clinique d'une telle exposition chez le patient dialysé et aucune étude n'a intégré le risque lié aux ClxBPA. C’est pourquoi, nous avons développé des biomarqueurs d'exposition en mettant au point des méthodes de dosage ultrasensibles du BPA et des ClxBPA dans les urines et le plasma. Ces biomarqueurs permettront d'étudier l'impact des différentes techniques de dialyse sur l'exposition des patients à ces PE
The health safety conditions for the practice of hemodialysis (HD) and hemodiafiltration (HDF) do not integrate the risks associated with micropollutants such as endocrine disruptors (ED). Dialysed patients are at risk of overexposure to Bisphenol A (BPA), a well-recognized ED, due to its occurrence in medical devices used during dialysis and to the risk of accumulation due to their renal impairment.In a first step we have confirmed BPA contamination in dialyzers and demonstrated, for the first time, that the water used in HD was a significant source of BPA contamination, via dialysate production. Furthermore, we highlighted the presence of chlorinated derivatives of BPA (ClxBPA), by-products of water chlorination known to have higher oestrogenic activity than BPA, in dialysis water. Then, We have demonstrated that HDF leads to a higher risk of exposure to ED than HD, via the contamination of the liquid of substitution perfused in patient. These results will allow manufacturers to take into account the risk of contamination to these ED as well as physicians and pharmacists involved in patient care.Very few data are available regarding the clinical impact of such exposition on dialysed patient and no study has included the risk arising from ClxBPA. Therefore, we have performed exposure biomarkers using ultra-sensitive analytical methods to determine BPA and ClxBPA concentration in urine and plasma. These biomarkers will allow studying the impact of different dialysis techniques on patient exposure to these ED

La prise en compte de la notion de la qualité de vie (QDV) du patient est révélatrice d'un changement profond dans la pratique médicale, notamment en néphrologie, pour les patients atteints d'insuffisance rénale chronique terminale (IRCT). Compte tenu de la prévalence, de l'incidence et de la mortalité de cette maladie en France, il paraissait important de pouvoir mesurer de façon pertinente et cohérente la QDV des patients atteints d'IRCT. La QDV liée à la santé constitue un indicateur pour apprécier les conséquences de cette maladie. En 2007, après une étude de revue de la littérature concernant les outils de mesure de la QDV des IRCT, il a été mis en évidence un manque de questionnaires spécifiques validés en langue française. Il existait donc un besoin réel d'évaluer la QDV de ces patients, et plus particulièrement celle des patients porteurs d'un greffon rénal fonctionnel.En 2008, une échelle spécifique a donc été développée et validée pour mesurer la QDV des patients greffés rénaux : le ReTransQol (ou RTQ). Après 5 années d'utilisation du RTQ dans diverses études nationales, cet outil a été amélioré et une nouvelle version a vu le jour: le RTQ V2. Après de nombreuses analyses, cette échelle présente actuellement de bonnes propriétés psychométriques et est validée auprès de diverses populations d'études. Le RTQ V2 sera d'ailleurs utilisé dans des études internationales (Brésil, Allemagne, Canada...), et une validation transculturelle est prévue. Le RTQ V2 est donc un outil de mesure spécifique de la QDV adapté pour une utilisation en routine auprès des patients porteurs d'un greffon rénal fonctionnel
The inclusion of the concept of quality of life (QOL) is indicative of a profound change in the way of practicing medicine, particularly in the field of nephrology for patients with end stage renal disease (ESRD). Given the prevalence, incidence and mortality of this disease in France, it seemed important, even essential, to measure properly, appropriately and consistently, the QOL of patients with ESRD. Health related quality of life (HRQOL) is therefore an important indicator of results to evaluate the consequences of this disease, the effect of medical procedures, treatment effects, or the impact of health policies.In 2007, after a study of literature concerning the assessment of QOL's scales of patients with ESRD, it was revealed a certain lack, quantitative or qualitative, of specific questionnaires for measuring QOL for ESRD patients validated in French, especially for patients with a functioning kidney transplant.In 2008, a specific scale has been developed and validated to measure the QOL of renal transplant recipients: the ReTransQol (Renal Transplant Quality of life questionnaire). After 5 years of use and application of ReTransQol in different national studies, this tool has been improved and a new version was created: the ReTransQol V2 (or RTQ V2). After lots of analysis, this scale has currently good psychometric properties and has been validated in various populations. The RTQ V2 is also used in international studies (Brazil, Germany, Canada ...), and a cross-cultural validation of the scale is planned.The ReTransQol V2 is a specific tool to assess the HRQOL and is suitable for a routine use among renal transplant recipients

碩士
國防醫學院
公共衛生學研究所
103
Background: Chronic kidney disease (CKD) is a large and growing problem. It is also associated with increased risk of cardiovascular disease and end-stage renal disease (ESRD), which are potentially preventable through early identification and treatment of individuals at risk. Purpose: The aim of this study is to investigate the risk factors of dialysis therapy among patients with CKD stages 1-5, enrolled in Taiwan’s pre-ESRD disease management program. Material and methods: A total of 2310 patients with CKD at stages 1 to 5 were identified from nephrology clinics at the Tri-Service General Hospital from 2006 to 2013. Prognosis records of all patients were extracted from the baseline to ESRD diagnosed.To ensure the progression of CKD, we excluded 60 patients who are hereditary kidney disease. It is a population-based study.The primaryoutcome was progression to chronic dialysis (ESRD). Predictors for this outcome were evaluated using cause-specific Coxproportional hazards models. Results: In our study, the hazard ratios of these characteristics include age, serum creatine, urea nitrogen and diabetes are significant higher between these patients of the cohort. In CKD stage 3, serum albumin, hemoglobin, diabetes and hyperlipidemia are risk factors to dialysis. In CKD stage 4, age, hemoglobin, serum creatine and diabetes are risk factors to dialysis. In CKD stage 5, serum creatine, serum calcium, diabetes and hypertention are risk factors to dialysis. Conclusion: This study identified the risk factors of CKD progressing to ESRD in this program, suggesting that a more effective pre-ESRD disease management program would be more than just a renal program. It is hoped that if implemented widely, the comprehensive protective strategy might not only delay the need for renal dialysis treatment but might actually prevent patients from ever reaching ESRD.

碩士
國立臺灣大學
會計與管理決策組
103
Since the launch of the National Health Insurance (NHI) program in Taiwan, the financial issue of healthcare has gained great importance especially under the global budget system. Any treatment plan following evidence-based medicine (EBM) should also base on a reasonable budget. Therefore, in the present work, we evaluate the economical reasonability of National Health Insurance Chronic Kidney Diseases Comprehensive Care System Plan from both microeconomic and macroeconomic perspectives in order to strike a balance between and create a win-win situation. In Chapter 3 and 5, we evaluate the cost-effectiveness of Pre-ESRD patient care and health education programs in delaying the progress of chronic kidney diseases from a macroeconomic perspective using the data from National Health Insurance Research Database. We first review the report of Dr. Shang-Zhi Huang (2014). It was reported that comparing the patients under Pay for Performance (P4P) plan with control group (non-P4P), patients in P4P(Pay for Performance) group had better clinical outcomes including survival rate (p<0.01), delayed onset of dialysis (p<0.01), and higher rate of peritoneal dialysis (p<0.01) but cost significantly more medical resources including outpatient expenditure (p<0.001) and emergency expenditure (p<0.001) after 5-year follow-up. However, in the present work, after calibrating the medical expenditure with survival curve and performing re-evaluation on the reasonability of expenditure items, we showed that the high-cost of P4P plan came from its lower mortality rate and higher rate of dialysis. Furthermore, after subtracting the cost for dialysis, the medical expenditures between 2 groups have no differences (p=0.8084). In Chapter 4, we discussed the care process of a chronic kidney disease patient under the Pre-ESRD patient care and health education programs and performed a cost analysis from the perspective of a primary-care physician. After considering the personnel cost, material cost, equipment depreciation and overhead cost, we showed that a primary-care physician participating the Pre-ESRD program could hardly strike a balance between income and expenditure. Dialysis cost about 35 billion dollars annually in Taiwan, representing 5.8% of annual health insurance global budget, and is an important resource-utilizing disease. The burden of chronic kidney diseases mainly comes from dialysis and the complications of CKD including cardiovascular diseases and diabetes. We recommended that effective management of kidney disease is the only possible way to improve the cost-effectiveness of the comprehensive medical care program for early-stage kidney disease.

碩士
中國醫藥大學
公共衛生學系碩士班
101
Background: The prevalence of end-stage renal disease (ESRD) in Taiwan has been the highest in the world for more than a decade since 2001. However, studies on the prognosis of chronic kidney disease (CKD) by stage are limited. This study evaluated the risk factors of ESRD and fatality for patients with stages 3, 4 and 5 of CKD. Methods: A total of 4702 patients with CKD at stages of 3-5 were identified from nephrology clinics at the Taichung Veteran General Hospital from December 6, 2001 to December 31, 2011. Prognosis records of all patients were extracted from the baseline to July 31, 2012, ESRD diagnosed, death or loss to follow-up. We used Cox models to identify risk factors associated with ESRD and deaths by stage and age, and used Kaplan-Meier method to measure the cumulative ESRD incidence and fatality for CKD patients. Results: Our study subjects consisted of 64% of male CKD patients, with 60% of patients over 65 years and 39% having diabetes. The incidence of ESRD in CKD patients at stages 3, 4, 5 were 1.95%, 10.6%, 46.7%, with fatalities of 4.56%, 6.23%, 4.69%, respectively. The elderly were at a lower risk for ESRD, but at higher risk for death, than youngers. Diabetic patients were at higher risks than non-diabetic patients for ESRD and death. Patients with hypertension or hyperlipidemia had a lowered risk for death. Conclusion: The risk of ESRD for patients with CKD increases with advanced stage. But the differences in fatality are not so acute. The elderly CKD patients are less prone to ESRD, but at an elevated risk of death.

碩士
臺灣大學
醫療機構管理研究所
98
Objective: To explose the effect of time variables, individual features and economis status, and cross level in paients who have Chronic Kidyne Disease (CKD) to become End Stage Renal Dialysis (ESRD). Method: The study design adpated retrospective study analysis. All variables were abtained from National Health Insurance Database.Time variables meant the vaiables'' status were changed with timet hat were including time, time squared, and CCI. Individual variables were including gender, occupation, living area, salary, and the accessing of health care resource. The CKD samples were patients who the disease was confirm with ICD-9-CM code. Growth model of Hierarchical Linear analysis was used in the study, including random coefficient model, and intercept as outcome model. Result: Excluding the missing data, the CKD samples were 5931. Until 2008, 132 of them were become ESRD. In hierarchical linear analysis, discovering time variables were related to ESRD. When controlling time variables, individual variables were related to intercept as outcome model. It showed that living in south area, proverty and unstable work, and low income were related to ESRD. Conculsion: Time variables and individual variables would cause the patient who has CKD to become ESRD.

碩士
國立臺灣大學
預防醫學研究所
98
Abstract Background: Diabetic patients with chronic kidney disease were at high risk of end stage renal disease. Previous studies showed that HMG-CoA reductase inhibitors (statins) could reduce proteinuria in patients with chronic kidney disease and slow the progression of renal function deterioration. In 2010, one population based cohort study in England revealed that statin increased the risk of acute renal failure. Till now, few studies investigate the effect of statin on the progression of chronic kidney disease to end stage renal disease。Therefore, our aim is try to identify whether statins could slow the progression of chronic kidney disease to end stage renal disease in diabetic patients by using big BNHI (Bureau of National Health Insurance) claim database. Materials and Methods: This is a retrospective cohort study using 2000 National Health Insurance diabetes cohort database. We identified 21719 diabetic patients with chronic kidney disease in 2002. Patients who used statin in 2002 were classified as statin user group and those who did not use statin in 2002 were classified as non-user group. The first statin prescription date in 2002 was defined as index date in statin users. We assigned a day which was chosen by the same distribution in statin users group as index date in non-users. Patients who had cancer or AIDS in 2002 were excluded. Patients who used statins or had end stage renal disease before index date were excluded, too. Total 13272 diabetic patients with chronic kidney disease were analyzed in our study. There were 1637 statin users and 11635 patients were non-users. Patients’ comorbidities and medical resource utilization were used to construct propensity score. Statin user group and non-user group are matched by propensity score. After matching for propensity score, there were 1637 statin users and non-users. Cox proportional hazard model was used to discover the hazard ratio of end stage renal disease and all cause mortality between these 2 groups. Sensitivity analysis was done by excluding patients with follow up time less than one year to test the robustness of study result. Result: End stage renal disease outcome analysis: The follow-up person-years in statin users were 3303.4 and the annual incidence rate was 0.058. The follow-up person-years in non-users were 3749.9 and the annual incidence rate was 0.041. The end stage renal disease hazard ratio between these 2 group was 1.36(1.10-1.68). Sensitivity analysis showed that the hazard ratio is 1.34 (1.07-1.68). Mortality outcome analysis: The follow-up person-years in statin users were 3447.9 and the annual incidence rate was 0.037. The follow-up person-years in non-users were 3926.6 and the annual incidence rate was 0.071. The mortality hazard ratio between these 2 group was 0.51(0.41-0.63). Sensitivity analysis showed that the hazard ratio is 0.45 (0.33-0.61). Conclusion: Our study showed that statins decrease the risk of mortality in diabetic patients with chronic kidney disease. On the other hand, the result of increasing risk of end stage renal disease in statin users needed further investigation because of residual immortal time bias.

碩士
中臺科技大學
醫療暨健康產業管理系碩士班
101
Chronic kidney disease (CKD) and end-stage renal disease (ESRD) have become major health problems over the world in recent years. According to 2012 USRDS annual report, the prevalence and incidence of ESRD was ranked first and fourth respectively in Taiwan in 2010. Kidney transplantation is the most effective and efficient method for ESRD; however, only few waiting patients could obtain cadaver kidneys. Living related kidneys transplantation became a feasible method because the deficiency of cadaver kidneys and too much expenditure resulting in the argument of distributive justice. In this study, hemodialysis and peritoneal dialysis patients in a medical center located in central Taiwan were selected to explore the knowledge, attitude, and practice of living related kidneys transplantation among hemodialysis and peritoneal dialysis patients and other associated factors. Self-administered structured questionnaire was adopted in this study. Self-administered structured questionnaire contained individual patient characteristics, knowledge, attitude, and willingness to living related kidneys transplantation. All the statistics was analyzed with SPSS 18.0 software package. According to the findings, the part of living related kidney transplant knowledge was scored 75.9 points ( the full score is 100 points), which indicates the subjects lack surgical knowledge and kidney transplants legal knowledge. As for the aspect of attitude, the adequacy of obtaining the information about kidney transplantation from a living relative donor was scored the lowest. The subjects’ anxiety about the donor’s surgical risk and postoperative life is apparently higher than that about the anxiety about their own surgical risk. The subjects with different backgrounds, such as those who perform peritoneal dialysis, with education levels above college, economic independence, isolation, in possession of commercial health insurance, organ donation and transplant-related experience, waiting for donor registration, and without comorbidity in diabetes, heart disease and stroke , showed significant differences. The subjects with education levels above college, single, employment currently and willingness to accept kidney transplantation from a living relative donor scored much higher on the attitude. The female subjects, aged 40-49, who live with their families, with economic dependence, without comorbidity in hypertention, have lung disease and poor eyesight, relatives of those who are willing to donate kidney showed great anxiety. As for the female subjects, raising a child, with economic independence, diagnosed with stones comorbidity disease, and with willingness to accept kidney transplantation from a living relative donor, the result of their questionnaires scored higher as well. The finding indicates that ESRD patients’ knowledge on kidney transplantation from a living relative donor is highly related to their attitude toward it. In addition, their attitude and concerns toward it have great impact on their willingness whether to accept kidney transplantation from a living relative donor. According to the findings in this study, the suggestions are as follows:(1) Government health agencies should set up a dedicated unit to promote organ donation by living relatives, and encourage medical institutions to participate in the promotion. Besides, by legislation, the NHI should waive the copayment of predonation tests and donation surgery to reduce donors’ burdens and worries and enhance donor's social welfare measures and medical protection. Moreover, the authorities should hold more campaigns on the knowledge on kidney transplantation from a living relative donor.(2) Medical staff in dialysis units should constantly take the initiative to provide living relative kidney transplant information for the patients who received dialysis treatment for ESRD patients and their families.(3)Transplant-related health education content of the related knowledge in transplant laws, surgical risk and assessment processes can be more clearly explained and linked with the network resources and websites to major hospitals.

by Tong Lai Wah, Christina.
Thesis (M.Phil.)--Chinese University of Hong Kong, 1999.
Includes bibliographical references (leaves 101-112).
Abstracts in English and Chinese.
Title Page --- p.i
Authorization Page --- p.ii
Signature Page --- p.iii
Acknowledgements --- p.iv
Table of Contents --- p.v-viii
List of Figures --- p.ix
List of Tables --- p.x
List of Append --- p.ix xi
Title Page --- p.xii
Abstract --- p.xiii
Chapter 1 --- Introduction --- p.14-15
Chapter 2 --- Literature Review --- p.16-24
Chapter 2.1 --- Introduction
Chapter 2.2 --- End-stage renal disease
Chapter 2.3 --- Continuous ambulatory peritoneal dialysis
Chapter 2.4 --- Patient participation
Chapter 2.4.1 --- Definition of participation
Chapter 2.4.2 --- Benefits of participation
Chapter 2.4.3 --- Problems of patient participation
Chapter 2.4.4 --- Application of patient participation
Chapter 2.5 --- Conclusion
Chapter 3 --- Methodology --- p.25-43
Chapter 3.1 --- Introduction
Chapter 3.2 --- Overview of grounded theory
Chapter 3.3 --- Procedures
Chapter 3.3.1 --- Data generation
Chapter - --- Sampling
Chapter - --- Data gathering
Chapter - --- Data recording
Chapter 3.3.2 --- Data analysis
Chapter - --- Open coding
Chapter - --- Constant comparative analysis
Chapter - --- Categorization
Chapter - --- Axial coding
Chapter - --- Theoretical sensitivity
Chapter - --- Memoing
Chapter 3.3.3 --- Theory construction
Chapter - --- Core category
Chapter 3.4 --- Method application
Chapter 3.4.1 --- Data collection
Chapter - --- Sampling
Chapter - --- Interview
Chapter - --- Recording
Chapter 3.4.2 --- Data analysis
Chapter - --- Open coding
Chapter - --- Constant comparative analysis
Chapter - --- Categorization and Axial coding
Chapter - --- Theoretical sensitivity
Chapter - --- Memoing
Chapter 3.4.3 --- Theoretical construction
Chapter - --- Concept formation
Chapter - --- Concept development
Chapter 3.5 --- Credibility & Trustworthiness
Chapter 3.6 --- Conclusion
Chapter 4 --- Findings --- p.44-72
Chapter 4.1 --- Introduction
Chapter 4.2 --- Core category: Integrative Restructuring
Chapter 4.3 --- Emotional Labour
Chapter 4.3.1 --- Entering the active zone
Chapter (a) --- Conditions to go into active zone
Chapter (b) --- Outcomes of emotional labour
Chapter (c) --- Strategies used for emotional labour
Chapter - --- Letting go of emotions
Chapter - --- Aligning cognitive consistency
Chapter - --- Maximizing ego
Chapter - --- Locating self
Chapter - --- Boosting power
Chapter i. --- Active control
Chapter ii. --- Building positive expectancies
Chapter iii. --- Covariance to positive expectancies
Chapter 4.3.2 --- Retreating into comfort zone
Chapter (a) --- Contexts of comfort zone
Chapter (b) --- Conditions to build comfort zone
Chapter (c) --- Strategies used within comfort zone
Chapter - --- Defending
Chapter - --- Relinquishing
Chapter - --- Anchoring
Chapter 4.3.3 --- Migrating between the two zones
Chapter (a) --- Conditions to initiate the move
Chapter (b) --- Covariance to the movement
Chapter (c) --- Strategies to make progress
Chapter 4.4 --- Conclusion
Chapter 5 --- Discussion --- p.73-92
Chapter 5.1 --- Introduction
Chapter 5.2 --- Theoretical framework
Chapter 5.3 --- Core category: Integrative Restructuring
Chapter 5.4 --- Variables affecting the move to active zone
Chapter 5.4.1 --- Preparations
Chapter 5.4.2 --- Support
Chapter (a) --- Source of support
Chapter (b) --- Context of support
Chapter (c) --- Effects of support
Chapter (i) --- Effects upon support-seekers
Chapter (ii) --- Supporter's reaction to support-giving relationship
Chapter 5.4.3 --- Commitment
Chapter (a) --- Perception of the situation
Chapter (b) --- Cultural influences
Chapter 5.4.4 --- Control
Chapter 5.5 --- Conclusion
Chapter 6 --- Concluding Chapter --- p.93-100
Chapter 6.1 --- Limitations
Chapter 6.2 --- Implications
Chapter 6.2.1 --- Practice
Chapter 6.2.2 --- Research
Chapter 6.2.3 --- Teaching
Chapter 6.2.4 --- Policy Making
Chapter 6.2.5 --- Summary
Chapter 6.3 --- Future research
Chapter 6.4 --- Reflections upon the study
Chapter 6.5 --- Conclusion
References --- p.101-112

The surgical management of renal masses involves either radical nephrectomy (RN) or partial nephrectomy (PN). The relationship between treatment choice and definitive outcomes of CKD are lacking. Our aim was to examine whether PN is associated with a lower risk of end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). We performed a population-based, retrospective cohort study with data from administrative databases in the province of Ontario, Canada. We included individuals with renal cell carcinoma diagnosed between 1995 and 2010. Cox proportional hazards, propensity score, and competing risks models were used to assess the impact of treatment. PN compared to RN reduces the risk of ESRD in a modern cohort of patients (2003-2010). PN is associated with a lower risk of CKD, reduced cardiac morbidity, and improved overall survival. We provide further evidence for the benefit of PN compared to RN, particularly related to definitive outcomes of renal failure.

Using Ontario health administrative data, we identified 12,143 adults with chronic kidney disease (CKD) who received outpatient nephrology care prior to start of renal replacement therapy (RRT) in order to study the effect of care-related factors in predicting late start of predialysis care (PDC, defined as first outpatient nephrology visit <6 months prior to RRT start) and to explore covariates which further quantify the PDC received. Lack of an usual provider of primary care (OR 0.76; 95%CI 0.66, 0.87) predicted late start of PDC. In addition to late start of PDC, number of nephrology visits (OR 0.97 per visit; 95% CI 0.96, 0.98), and having seen a nephrologist in only 1 or 2 of the 6 months prior to RRT start (OR 1.33; 95%CI 1.18, 1.51), were also independent predictors of one-year mortality, suggesting that other measures of PDC are needed to better characterize the care received.