Academic literature on the topic 'End Stage Kidney Disease (ESKD)'

Background and Purpose— People with end-stage kidney disease (ESKD) are at greater risk of stroke. We aimed to compare stroke mortality between the ESKD population and the general population. Methods— We included all patients with incident ESKD in Australia, 1980 to 2013, and New Zealand, 1988 to 2012. The primary cause of death was ascertained using data linkage with national death registers. We produced standardized mortality ratios for stroke deaths, by age, sex, and calendar year. Results— We included 60 823 patients with ESKD, where 941 stroke deaths occurred during 381 874 person-years. Patients with ESKD had >3× the stroke deaths compared with the general population (standardized mortality ratio, 3.4; 95% CI, 3.2–3.6), markedly higher in younger people and women. The greatest excess was in intracerebral hemorrhages (standardized mortality ratio, 5.2; 95% CI, 4.5–5.9). Excess stroke deaths in patients with ESKD decreased over time, although were still double in 2013 (2013 standardized mortality ratio, 2.1; 95% CI, 1.5–2.9). Conclusions— People with ESKD experience much greater stroke mortality with the greatest difference for women and younger people. However, mortality has improved over time.

BackgroundCKD progression can be a cause and potentially a consequence of anemia. Previous studies suggesting that anemia is associated with CKD progression have not used methodologic approaches to address time-dependent confounding.MethodsWe evaluated the association of anemia (defined using World Health Organization criteria of hemoglobin <12 g/dl in women and <13 g/dl in men) with incident ESKD and all-cause death in individuals with CKD using data from the Chronic Renal Insufficiency Cohort Study. Marginal structural models were used to account for time-dependent confounding.ResultsAmong 3919 participants, 1859 (47%) had anemia at baseline. Over median follow-up of 7.8 years, we observed 1010 ESKD events and 994 deaths. In multivariable analyses, individuals with anemia had higher risk for ESKD compared with those without (HR, 1.62; 95% CI, 1.24 to 2.11). In stratified analyses, the increased risk for incident ESKD with anemia was observed in males (HR, 2.15; 95% CI, 1.53 to 3.02) but not females (HR, 1.20; 95% CI, 0.82 to 1.78). The association between anemia and ESKD was significant among all racial/ethnic groups except non-Hispanic blacks (non-Hispanic white, HR, 2.16; 95% CI, 1.53 to 3.06; Hispanic, HR, 1.92; 95% CI, 1.04 to 3.51; others, HR, 2.94; 95% CI, 1.16 to 7.44; non-Hispanic black, HR, 1.39; 95% CI, 0.95 to 2.02). There was no association between anemia and all-cause death.ConclusionsIn this cohort, anemia was independently associated with increased risk for incident ESKD. Future work is needed to evaluate the mechanisms by which anemia leads to CKD progression as well as the effect of novel therapeutic agents to treat anemia.

Abstract Objectives To determine how often end-stage kidney disease (ESKD) is implicated as a cause of death (COD) at autopsy. Methods We searched our autopsy database (2007-2017) using queries “end-stage renal disease,” “end-stage kidney disease,” “ESRD,” “chronic renal disease,” and “chronic kidney disease.” Final diagnosis and summaries were reviewed to determine if ESKD was appropriately correlated with the COD. Cases in which the COD was unrelated to kidney function were excluded. Results Eighty-five patients with a history of ESKD and histologic confirmation thereof were identified. Their CODs were cardiovascular (36%), infection/sepsis (41%), pulmonary (6%), gastrointestinal/hepatic (2%), central nervous system (3%), other systemic disease (7%), and unspecified (5%). ESKD was implicated as a contributing COD in 24 (28%) cases. Conclusions ESKD is often overlooked at autopsy, particularly in patients with cardiovascular or infectious disease. Accurate documentation of ESKD contributing to mortality is important for education, counseling, record maintenance, and directing research efforts.

Background and objectivesWe investigated the incidence of ESKD after surgical management of kidney cancer in the Australian state of Queensland, and described patterns in the initiation of kidney replacement therapy resulting from kidney cancer across Australia.Design, setting, participants, & measurementsAll newly diagnosed cases of kidney cancer in the Australian state of Queensland between January of 2009 and December of 2014 were ascertained through the Queensland Cancer Registry. There were 2739 patients included in our analysis. Patients who developed ESKD were identified using international classification of disease–10–coded hospital administrative data. Incidence rate and 3-year cumulative incidence were calculated, and multivariable Cox proportional hazards models were used to identify factors associated with ESKD. Additional descriptive analysis was undertaken of Australian population data.ResultsThe incidence rate of ESKD in all patients was 4.9 (95% confidence interval [95% CI], 3.9 to 6.2) per 1000 patient-years. The 3-year cumulative incidence was 1.7%, 1.9%, and 1.0% for all patients, and patients managed with radical or partial nephrectomy, respectively. Apart from preoperative kidney disease, exposures associated with increased ESKD risk were age≥65 years (adjusted hazard ratio [aHR], 2.0; 95% CI, 1.2 to 3.2), male sex (aHR, 2.3; 95% CI, 1.3 to 4.3), preoperative diabetes (aHR, 1.8; 95% CI, 1.0 to 3.3), American Society of Anesthesiologists classification ≥3 (aHR, 4.0; 95% CI, 2.2 to 7.4), socioeconomic disadvantage (aHR, 1.6; 95% CI, 0.9 to 2.7), and postoperative length of hospitalization ≥6 days (aHR, 2.1; 95% CI, 1.4 to 3.0). Australia-wide trends indicate that the rate of kidney replacement therapy after oncologic nephrectomy doubled between 1995 and 2015, from 0.3 to 0.6 per 100,000 per year.ConclusionsIn Queensland between 2009 and 2014, one in 53 patients managed with radical nephrectomy and one in 100 patients managed with partial nephrectomy developed ESKD within 3 years of surgery.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_09_28_CJASNPodcast_18_1_.mp3

Background: It was recently reported that the severity of coronary and carotid atherosclerosis in patients with end-stage kidney disease (ESKD) has improved over the last two decades. However, the frequency of coronary artery events observed at the initiation of dialysis remains high. Summary: Recently, 5 different clinical types of acute myocardial infarction (MI) were introduced in the third universal definition of MI. Type 2 MI, known as secondary MI, is a more heterogeneous entity, where a condition other than coronary artery narrowing contributes to an acute imbalance in oxygen supply and demand. In patients with chronic kidney disease, it has been demonstrated that type 2 MI is more common than type 1 MI, which is associated with coronary occlusive disease. It is suspected that patients with ESKD also often have type 2 MI. Factors associated with incremental increases in oxygen demand may cause myocardial ischemia in ESKD. Key Messages: Significant epicardial coronary narrowing might not be a necessary precursor of myocardial ischemia in ESKD. To prevent ischemic heart disease and improve prognosis in patients with ESKD, we need to pay attention not only to coronary stenotic lesions, but also to the factors associated with the induction of an imbalance in myocardial oxygen supply and demand.

Background: Cardiorenal syndrome (CRS) in patients with end-stage kidney disease (ESKD) represents mainly cardiovascular disease (CVD) due to various complications associated with renal dysfunction—defined as type 4 CRS by Ronco et al.—because the effect of cardiac dysfunction on the kidneys does not need to be taken into consideration, unlike in non-dialysis dependent chronic kidney disease (CKD). Summary: Patients with ESKD are often in a state of chronic inflammation due to the upregulation of proinflammatory cytokines. Chronic inflammation leads to malnutrition and consequently to vascular endothelial dysfunction and vascular calcification, which is referred to as malnutrition-inflammation-atherosclerosis (MIA) syndrome and acts as a major risk factor for CVD. Anemia also plays a crucial role in CVD, and individuals with erythropoietin-resistant anemia have a particularly high risk of CVD. However, caution is emphasized because not only anemia itself, but also the overtreatment of anemia with erythropoiesis-stimulating agents aimed at elevating hemoglobin to ≥13 g/dl can also increase the risk of CVD. In CKD-mineral and bone disorder (CKD-MBD), phosphate load triggers the interactions between various factors such as calcium, parathyroid hormone, vitamin D, and fibroblast growth factor 23, promoting vascular calcification and thus becoming a risk factor for CVD. Key Messages: In addition to traditional atherosclerosis risk factors such as hypertension, diabetes, and dyslipidemia, the involvement of MIA syndrome, anemia, and CKD-MBD accompanying CKD have also become a focus for investigation as major players in CRS in patients with ESKD.

In patients with end-stage kidney disease (ESKD), when there maybe situations where dialysis does not offer benefits in terms of survival or health-related quality of life, dialysis should not be viewed as the default therapy. Such patients can be offered comprehensive conservative care as an alternative to dialysis. Conservative (nondialytic) management of ESKD includes careful attention to fluid balance, treatment of anemia, correction of acidosis and hyperkalemia, blood pressure, and calcium/phosphorus metabolism management and dietary modification. Individualized symptom management and supportive care are crucial to maximize the quality of life. We propose that model of comprehensive conservative care in ESKD should manage both diseases as well as provide supportive care. Facilitating implementation of comprehensive conservative care requires coordination between nephrology and palliative care at patient, professional, administrative, and social levels to maximize benefit with the motto to improve the overall quality of life.

Atrial fibrillation (AF) is the most common arrhythmia in the general population and it has been found to have a higher prevalence in end-stage kidney disease (ESKD). It is associated with a higher risk of stroke and mortality compared to those without AF. Patients with ESKD have generally been excluded from randomized controlled trials (RCTs) evaluating the efficacy of anticoagulation in reduction of stroke risk. Current observational evidence for anticoagulation for AF in the ESKD population has yielded conflicting results, but in aggregate favours a lack of benefit in stroke risk reduction with an increase in bleeding risk. There are also reports that warfarin use in ESKD patients on dialysis is associated with greater International Normalised Ratio (INR) variability and increased risk of vascular calcification and calciphylaxis (uraemic calcific arteriolopathy). RCTs are required to assess the net clinical benefit of anticoagulation in this group.

Patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) experience an increased risk of cerebrovascular disease and cognitive dysfunction. Hemodialysis (HD), a major modality of renal replacement therapy in ESKD, can cause rapid changes in blood pressure, osmolality, and acid-base balance that collectively present a unique stress to the cerebral vasculature. This review presents an update regarding cerebral blood flow (CBF) regulation in CKD and ESKD and how the maintenance of cerebral oxygenation may be compromised during HD. Patients with ESKD exhibit decreased cerebral oxygen delivery due to anemia, despite cerebral hyperperfusion at rest. Cerebral oxygenation further declines during HD due to reductions in CBF, and this may induce cerebral ischemia or “stunning.” Intradialytic reductions in CBF are driven by decreases in cerebral perfusion pressure that may be partially opposed by bicarbonate shifts during dialysis. Intradialytic reductions in CBF have been related to several variables that are routinely measured in clinical practice including ultrafiltration rate and blood pressure. However, the role of compensatory cerebrovascular regulatory mechanisms during HD remains relatively unexplored. In particular, cerebral autoregulation can oppose reductions in CBF driven by reductions in systemic blood pressure, while cerebrovascular reactivity to CO2 may attenuate intradialytic reductions in CBF through promoting cerebral vasodilation. However, whether these mechanisms are effective in ESKD and during HD remain relatively unexplored. Important areas for future work include investigating potential alterations in cerebrovascular regulation in CKD and ESKD and how key regulatory mechanisms are engaged and integrated during HD to modulate intradialytic declines in CBF.

Background. Anemia and pancytopenia are not uncommon in patients with chronic kidney disease (CKD). Nevertheless, there is insufficient literature analyzing bone marrow pathology in patients with CKD or end-stage kidney disease (ESKD) receiving dialysis. Methods. This observational cohort study included 22 patients with ESKD and 23 patients with CKD that received bone marrow biopsy and aspiration at Chang Gung Memorial Hospital. Demographic, hematological, and biochemical data were collected at the time of bone marrow study for analysis. Results. Bone marrow aspiration demonstrated that patients with ESKD had a lower percentage of blasts than patients with CKD (0.52 ± 0.84 versus 1.06 ± 0.78 %, p = 0.033). Bone marrow biopsy revealed that the overall incidence of hypocellular bone marrow was 55.6%. Furthermore, patients with ESKD had higher proportion of hypocellular bone marrow than patients with CKD (72.7% versus 39.1%, p = 0.023). In a multivariate logistic regression model, it was revealed that ESKD status (odds ratio 9.43, 95% confidence interval 1.66–53.63, p = 0.011) and megakaryocyte count within bone marrow (odds ratio 0.48, 95% confidence interval 0.29–0.79, p = 0.004) were significant predictors for bone marrow hypocellularity. Conclusion. Bone marrow hypocellularity is common in patients with kidney dysfunction. Hypocellular marrow occurs more frequently in patients with ESKD than patients with CKD.

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.

Background:End Stage Kidney disease (ESKD) patients must follow unique dietary restrictions. The most onerous of these is the need to restrict fluid intake. The ramifications of poor fluid control include increased mortality and morbidities, frequent hospitalizations with diagnoses of heart failure and pulmonary edema, increased hospital length of stay, and increased total cost of care. Fluid intake control is a bedrock component of treatment for ESKD Patients, but continues to be a major challenge for patients, healthcare providers, and organizations. The ramifications of poor fluid control include increased mortality and morbidities, frequent hospitalizations and increased total cost of care. The goal of this work is to investigate the feasibility of leveraging smartwatch technology to monitor fluid consumption of ESKD patients outside of the clinic. Adequate assessment of fluid intake of patients with ESKD on HD and offering timely feedback to patients and clinicians has the potential of curbing the extra fluid intake, hence reduce mortality and morbidity, and hopefully cut the costs of the need of frequent hospitalizations and/or extra dialysis treatments.Methods:We have designed a smartwatch app called Fluisense (available on Android play store,, https://play.google.com/store/apps/details?id=com.mob.fluisense) to help ESKD patients monitor their fluid intake. Fluisense helps patients record Fluid intake logs in an intuitive manner. Fluisense also collects sensor data such as mobility, acceleration, and heart rate to investigate biomarkers indicative of fluid overload. To the best of our knowledge, this is the first work leveraging smartwatches to monitor fluid accumulation of ESKD patients.N=15 ESKD patients were given an Android smartwatch with Fluisense pre-installed and were asked to log their fluid intake through the app by choosing from a list of predefined volumes each time they consume any liquid. The app computed and displayed the self-reported daily volume intake to help patients monitor their own fluid consumption. Patients received text messages twice a day (9am and 8pm) to remind them to use the watch. We also recorded patients’ weights before and after each of the thrice weekly dialysis sessions. The sum of self-reported interdialytic fluid intake was computed and compared against the interdialytic weight gain recorded in the clinic.Results: Patients recorded Fluids in 214 days out of 259 total days (i.e., 83% compliance rate). The average self-reported interdyalitic fluid consumption is 51 oz +/-64, and the average interdialytic weight gain is 2.67 kg +/- 1.56. We found a moderate but significant correlation between the self-reported fluid volumes and the interdialytic weight gain (r=0.363, P<0.001, r2=0.06). A deep learning method has also been designed to predict the interdialyctic weight gain from sensor data. Results validated through leave one subject out cross validation show an F1 score of 91 at predicting the level of weight change.Conclusion: Leveraging smartwatch-based sensing technology is a promising solution for fluid monitoring of ESKD patients. This can be related to the ease of utilization of this technology and the ecological validity of its measurements given they are collected close to when they happen, reducing recall biases.

Hemodialysis (HD) is a necessary treatment for end-stage kidney disease (ESKD) patients in order to prevent cardiovascular morbidity and mortality that may be related to the hemodynamic effects of rapid ultrafiltration. Despite significant advances in HD technology, only half of ESKD patients treated with HD survive more than 3 years. Fluid management remains one of the most challenging aspects of HD care, with serious implications for morbidity and mortality. In this paper, we develop a novel algorithm to design real time optimal, robust ultrafiltration rates based on actual HD data to identifying the parameters of a fluid volume model of an individual patient during HD. Our design achieves, if exists, an optimal ultrafiltration profile for the identified nominal model under maximum ultrafiltration and hematocrit constraints and guarantees that these constraints are satisfied over a pre-defined set of parameter uncertainty. We demonstrate the robust performance of our algorithm through a combination of clinical data and simulations.

Kidney failure is a major issue in the United States. The numbers of kidney failure patients are rapidly increasing with the simultaneous rise in diabetes, obesity and hypertension1. Kidney transplantation has shown excellent results, but insufficiency of donors has been a limiting factor. Most end-stage renal disease (ESRD) patients depend on hemodialysis (HD) for survival which is highly expensive. On an average ESRD patients receive 3 dialysis treatment a week and 4 hours per treatment, i.e., approximately 12 hours a week. Technology has not yet reached to a state where all the kidney functions can be mimicked. The only major kidney function being performed in HD is toxin removal. Even the toxins are not being continuously removed from the patients. To compensate the toxin and fluid removal of a whole week within 12 hours, high volumes of fluid are removed in HD treatments. Patients suffer due to the high fluid removal in a short period of time. Also the patients are restricted from taking fluids between the HD treatments. More frequent HD can improve both survival rate and life quality of patients with chronic kidney disease since normal people has his kidneys functioning continuously. It is a well known fact that daily dialysis offers many benefits over regular intermittent HD1. But providing daily dialysis is not affordable currently. Therefore, new modes of delivering continuous renal support are required.

Chronic dialysis is a necessary treatment for end-stage kidney disease (ESKD) patients in order to increase life span, with hemodialysis (HD) being the dominant modality. Despite significant advances in HD technology, only half of ESKD patients treated with this modality survive more than 3 years. Fluid management remains one of the most challenging aspects of HD care, with serious implications for morbidity and mortality. Ultrafiltration has been associated with intradialytic hypotension, also associated with adverse outcomes. Therefore, removing a specified fluid volume to achieve an adequate balance without negative outcomes remains a critical challenge to improving patient outcomes. Therefore, it has been suggested that in addition to blood pressure information, routine HD treatments should include blood volume monitoring. Sensors integrated in dialysis machines are able to track the concentration of various blood components, such as hematocrit, with high accuracy and resolution and to derive a relative blood volume (RBV) changes. In this paper, we propose a novel algorithm to design an optimal, robust ultrafiltration rate profile based on identifying the parameters of a fluid volume model of an individual patient during HD and RBV sensor. Our design achieves, if exists, an optimal ultrafiltration profile for the identified nominal model under maximum ultrafiltration and hematocrit constraints, and guarantees that these constraints are satisfied over a pre-defined set of parameter uncertainty. We demonstrate the performance of our algorithm through a combination of clinical data and simulations.

End-Stage Renal Disease (ESRD) is a condition wherein the kidneys are incapable of removing toxins from the body. Over 660,000 Americans suffer from ESRD, with millions more in the early stages, known as chronic kidney disease [1]. The only cure for ESRD is a kidney transplant, but the majority of patients receive dialysis every 2–3 days to filter their blood while on the transplant waitlist. Efficient dialysis requires approximately 600 mL/min of flow, which is commonly achieved by directly connecting an artery to a vein in the arm. Such a shunt may be created with an intervening prosthetic graft or by suturing the vein to the artery directly (termed an arteriovenous fistula, or AVF). Though accepted as the gold standard, AVF’s may take >6 weeks to heal and become useable, and 35–50% will never become accessible [1]. Needle trauma to the AVF can weaken the vessel wall and produce aneurysms or hematomas, which leak blood, potentially causing infection or clotting off the AVF [2]. These complications are costly: hemodialysis patients on average cost Medicare over $84,000 per year, and Medicare is the primary payer for more than 80% of nearly 500,000 dialysis patients in the U.S. [1]. An improved dialysis access method is needed to address the clinical shortcomings and high costs associated with AVF’s. A device has been developed to improve clinical outcomes and to reduce the failure rates associated with AVF’s. This device is a type of vascular access port which integrates with the external wall of the venous portion of the AVF, providing structural support to the vessel and preventing the types of trauma which lead to aneurysmal dilation or hematoma formation. The top and bottom sections are implanted independently within the patient’s soft tissue, allowing them to separate gradually as the AVF dilates during maturation. The result is a palpable and easy-to-access port which should improve AVF longevity (Figure 1). Two unique design features were identified as key to the success of this vascular access port: 1. Type of membrane or seal 2. Proper tissue integration into the implant This technical brief examines the selection of the proper membrane or seal on the port.

End Stage Renal Disease (ESRD) is the degeneration of kidney function to remove uremic toxins from the blood. Currently there are over 484,000 sufferers of ESRD in the United States, with this figure predicted to rise to over 800,000 by 2020 [1]. The total cost of care for patients with ESRD was estimated to exceed 1 billion dollars in the United States [2]. A kidney transplant is the ideal solution for ESRD patients; however with the increasing number of ESRD patients the odds of receiving a donor kidney are poor. The alternative is hemodialysis. This process is involves the extraction of blood from the patient to an extracorporal machine. Blood is pumped at a rate of 350 mL/min to ensure effective dialysis. The blood is then returned to the body cleaned. The gold standard for hemodialysis access is the native arteriovenous fistula [3] with the most common type being the Brescia-Cimino fistula at the wrist [4]. In some subgroups the fistula performs poorly. In diabetics and the elderly, specifically over 70s [2] or can’t be constructed because of unsuitable blood vessels [5]. In this case an alternative is the synthetic AV graft. Made of polytetrafluoroethelyne, it has lower patency rates against the fistula [6] [7] mediated by the susceptibility to thrombosis induced by stenosis development and infection [7].The majority of stenosis development is within the venous anastomosis (kanterman1995). The formation of intimal hyperplasia (IH) leading to stenosis formation is caused by smooth cell proliferation and migration as a result of endothelial cells reacting to shear stress receptors. The development of IH has been linked to local hemodynamics and turbulence in the flow, which in turn are heavily influenced by the geometry of the graft.

End-stage renal disease (ESRD) occurs as a result of any renal injury that chronically decreases renal excretory and regulatory function. ESRD patients are most commonly treated with hemodialysis (HD) to manage their renal failure while awaiting kidney transplant. Current practices for maintenance of HD vascular access consist of arteriovenous fistulas (AVFs) or grafts (AVGs), which are both fraught with problems that compromise the patency and use of these surgically created shunts. The major cause of shunt failure is thrombosis caused by occlusion of the outflow venous anastomosis and draining vein. Intimal hyperplasia (IH), which consists of the thickening of the innermost layer of the vessel wall, is the initial pathological event leading to shunt stenosis/thrombosis and has been associated with the presence of flow disturbances and abnormal wall shear stress (WSS) at the graft-vein anastomosis. Therefore, the improvement of HD via the enhancement of vascular access patency requires the development of a novel vascular access technology preserving the normal hemodynamics of the native vein.

Review question / Objective: The objective of this study is to evaluate the clinical efficacy and safety as well as to summarize the current knowledge of difelikefalin in treatment of patients with CKD-aP based on the available clinical trials. Condition being studied: Chronic kidney disease-associated pruritus (CKD-aP), also known as uremic pruritus, is a condition that significantly reduces the quality of life of patients with end-stage renal disease. There were unmet needs in the treatment of this condition. Difelikefalin is a novel opioid agonist with high selectivity for kappa opioid re-ceptors (KOR) that has been shown to be effective in the treatment of this type of chronic pruritus.