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Chronic kidney disease is an urgent public health problem in the U.S., affecting 15% of all adults, and more than 740,000 have progressed to end-stage renal disease (ESRD), requiring life-sustaining renal replacement therapy (RRT). ESRD has devastating health, quality-of-life, and economic consequences, rendering most patients unable to maintain employment and costing Medicare $36 billion in 2017. Arguably, the most disadvantaged subgroup is the subset of patients that received no or minimal pre-ESRD nephrology care, which currently accounts for one third of the total ESRD population. This subgroup suffers increased morbidity and mortality, and has limited access to kidney transplantation, the optimal RRT. Despite this subgroup representing a large minority of the ESRD patient population, there has been no U.S.-based examination of their ESRD diagnosis experiences, coping styles and strategies, and RRT decision-making preferences. Therefore, we conducted a study that compared the ESRD diagnosis experiences, coping styles and strategies, and RRT decision-making preferences among patients with varying amounts of pre-ESRD nephrology care. We also assessed nephrologists’ current practices and perspectives on the manner and timing of RRT education for patients with varying amounts of pre-ESRD care. This mixed methods study provides a comprehensive understanding of the diagnosis experiences, coping styles and strategies, and RRT decision-making preferences of patients facing sudden and unexpected ESRD diagnosis. The study contributes important knowledge about this subgroup of patients that can influence and improve health care delivery. The results of this research will inform future intervention-based investigations to improve care for patients with minimal or no pre-ESRD nephrology care. / Public Health

Hyperhomocysteinemia (hHcys) is a widely known pathogenic factor in the progression of end-stage renal disease (ESRD) and it is also associated with an increased risk for injurious cardiovascular pathologies during ESRD. HHcys is linked to the formation and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, characterized as a critical early mechanism initiating the inflammatory response. NADPH oxidase (NOX)-derived reactive oxygen species (ROS) mediate the activation of the NLRP3 inflammasome in podocytes in response to elevated levels of homocysteine (Hcys) in vitro and in vivo. However, it remains unknown how NLRP3 inflammasome activation is triggered by NOX. The aim of the present study sought to determine the signaling cascade that triggers glomerular injury and sclerosis during hHcys mediated by Vav2, a guanine nucleotide exchange factor (GNEF). Using both genetic and pharmacological interventions of Vav2, we first tested whether this GNEF is involved in hHcys-induced NLRP3 inflammasome activation in podocytes by its role in activation of the Rac-1-NOX complex. Further, we explored whether pharmacological targeting of Vav2 activation may regulate NLRP3 inflammasome signaling pathway during hHcys-induced glomerular injury. We found that mice with hHcys (on the FF diet) or oncoVav2 (a constitutively active form of Vav2) transfection in the kidney exhibited increased colocalization of NLRP3 with apoptosis-associated speck-like protein (ASC) or caspase-1 and elevated IL-1β levels in glomeruli, indicating the formation and activation of the NLRP3 inflammasome. This glomerular NLRP3 inflammasome activation was accompanied by podocyte dysfunction and glomerular injury, even sclerosis. Local transfection of Vav2 shRNA plasmids significantly attenuated hHcys-induced NLRP3 inflammasome activation, podocyte injury, and glomerular sclerosis. In cultured podocytes, Hcys treatment and oncoVav2 transfection increased NLRP3 inflammasome formation and activation. This NLRP3 activation was inhibited by Vav2 shRNA, associated with reduction of Rac-1 activity and ROS production. Administration of NSC23766, a Rac-1 inhibitor substantially attenuated inflammasome formation, desmin expression and decreased podocin expression in glomeruli of hHcys mice. These results suggest that elevated Hcys levels activate Vav2 and thereby increase NOX activity, leading to ROS production. ROS trigger NLRP3 inflammasome activation, podocyte dysfunction and glomerular injury. Therefore, the present study defines a novel mechanism underlying hHcys-induced NLRP3 inflammasome activation and its progression to ESRD.

The progression of End Stage Renal Disease (ESRD) among type II diabetics is preventable, yet complications continue to plague many. Reports show that 29.1 million people (9.3%) in the United States have diabetes, and 40% of those individuals develop ESRD. Four research questions explored the relationship between ESRD, health literacy, and healthcare. Data from 2010-2015 from the National Institute of Health (NIH) was quantitatively analyzed. The conceptual framework was the revised health service utilization theory. The target population included 3939 diverse males and females between the ages of 20-75 diagnosed with type II Diabetes. Results from Chi-square, cross-tabulation, binary, and multinomial logistic regression revealed that there is a statistically significant relationship between inadequate health literacy and ESRD (p= <0.05), inadequate health literacy and healthcare services (p= <0.05), and healthcare services and development of ESRD (p=<.001). Findings exposed significant demographic co-factor differences. Males developed ESRD more than females, and African American and Hispanic populations were almost 2 times more likely than Caucasians to develop ESRD. As participants age, odds for developing ESRD increase about 2-3 times. Both race and education were significant predictors of inadequate health literacy. African Americans and Hispanics were 3 times more likely to have inadequate health literacy than Caucasian participants. Lower education increased the odds of having inadequate health literacy approximately 7.6 times. Results show that Caucasian participants had higher education levels and private health insurance, whereas African Americans and Hispanics had lower education and no insurance or Medicaid. Implications from this research show that social determinants among vulnerable populations are impacting an individual's health literacy and ability to adequately manage their health. Evidence from this study generates social change through recognition that health literacy is fundamental when attempting to prevent chronic disease complications and promote positive health.

The management and treatment of chronic diseases, such as end-stage renal disease, is often unproductive because of patients' poor adherence to treatment. The chronic care model toolkit is an Agency for Healthcare Research and Quality supported framework, associated with improved outcomes in patients living with chronic disease. The purpose of this project was to develop and plan an educational program using the chronic care model toolkit for the interdisciplinary clinical staff of a renal hemodialysis center. The goal of this project was to adapt team building between patients and their clinicians through the use of the chronic care model in order to improve patients' adherence to treatment. The educational program materials were developed, including a plan for future implementation over 6 weeks in 2-hour twice-weekly sessions. Program planning accounted for the mixed roles and responsibilities of the interdisciplinary clinical team members, who will share their knowledge among the team and act as patient advisors. The pretest and posttest materials were developed from the toolkit Team Health Audit Questionnaire, which can be used to evaluate staff learning after the program is delivered. Existing clinical metrics are tracked through a Quality Assessment Performance Improvement measure, which will be used to evaluate potential long term influences of the program on patient adherence and outcomes. The project may contribute to social change in practice by enhancing teamwork that has the potential to improve clinical outcomes. Future research should include longitudinal studies on team building using the chronic care model toolkit to determine if its adaption enhances team effort and contributes to a collaborative workforce that improves clinical outcomes.

<p>Diabetes mellitus (DM) is one of the leading causes of end stage renal failure. An increased susceptibility to renal ischemia/reperfusion (I/R)-injury was found in DM rats. Unilateral renal ischemia for as short as 20 minutes led to an irreversible progressive injury in DM kidneys, whereas the injury in non-DM kidneys was almost reversible. The renal I/R injury was characterized by anuria, infiltration of inflammatory cells, tubular atrophy, dilation of the remaining tubuli and tubulointerstitial fibrosis. Necrotic areas were found in the inner parts of the outer medulla and in the papilla. The renal medulla was the most vulnerable part of the kidney. This was seen both by the extent of fibrosis four and eight weeks after I/R and by the presence of TUNEL-positive (apoptotic) cells 6h after ischemia. Increased accumulation of HA and enhanced CD44 expression was seen after I/R in DM kidneys.</p><p>Treatment with long acting insulin 7-14 days before I/R, decreased the number of apoptotic cells in the renal medulla and protected renal function and morphology after the insult, while insulin treatment after the injury did not have any protective effect. Short acting insulin given 2-6 hours before I/R partially protected renal function but did not improve the morphological picture.</p><p>Treatment with the angiotensin II receptor type 1 blocker candesartan, the PAF-antagonist UR-12670, the immunosuppressive agents tacrolimus and cyclosporin A, or prednisolone did not improve the outcome of the renal I/R injury in DM. Injection of cobalt protoporphyrin (CoPP) intraperitoneally in order to induce an over-expression of heme oxygenase-1 (HO-1) resulted in a trend towards a better function in DM kidneys after I/R. However, the induction of HO-1 by intraperitoneal CoPP injection was not achieved in all rats, when examined by western blot.</p><p>In conclusion, unilateral renal I/R leads to a severe progressive injury in DM kidneys. Insulin treatment before ischemia, but not after, reduces the renal injury in DM rats. Studies using a more reliable administration of CoPP are required to decide if induction of HO-1 protects against renal I/R injury in DM.</p>

Diabetes mellitus (DM) is one of the leading causes of end stage renal failure. An increased susceptibility to renal ischemia/reperfusion (I/R)-injury was found in DM rats. Unilateral renal ischemia for as short as 20 minutes led to an irreversible progressive injury in DM kidneys, whereas the injury in non-DM kidneys was almost reversible. The renal I/R injury was characterized by anuria, infiltration of inflammatory cells, tubular atrophy, dilation of the remaining tubuli and tubulointerstitial fibrosis. Necrotic areas were found in the inner parts of the outer medulla and in the papilla. The renal medulla was the most vulnerable part of the kidney. This was seen both by the extent of fibrosis four and eight weeks after I/R and by the presence of TUNEL-positive (apoptotic) cells 6h after ischemia. Increased accumulation of HA and enhanced CD44 expression was seen after I/R in DM kidneys. Treatment with long acting insulin 7-14 days before I/R, decreased the number of apoptotic cells in the renal medulla and protected renal function and morphology after the insult, while insulin treatment after the injury did not have any protective effect. Short acting insulin given 2-6 hours before I/R partially protected renal function but did not improve the morphological picture. Treatment with the angiotensin II receptor type 1 blocker candesartan, the PAF-antagonist UR-12670, the immunosuppressive agents tacrolimus and cyclosporin A, or prednisolone did not improve the outcome of the renal I/R injury in DM. Injection of cobalt protoporphyrin (CoPP) intraperitoneally in order to induce an over-expression of heme oxygenase-1 (HO-1) resulted in a trend towards a better function in DM kidneys after I/R. However, the induction of HO-1 by intraperitoneal CoPP injection was not achieved in all rats, when examined by western blot. In conclusion, unilateral renal I/R leads to a severe progressive injury in DM kidneys. Insulin treatment before ischemia, but not after, reduces the renal injury in DM rats. Studies using a more reliable administration of CoPP are required to decide if induction of HO-1 protects against renal I/R injury in DM.

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

End stage renal disease (ESRD) patients have an excess cardiovascular risk, above that predicted by traditional risk factor models. Despite the advances in both Cardiovascular disease (CVD) management and renal replacement therapy (RRT), there still is a major burden of cardiovascular mortality and morbidity in the chronic kidney disease (CKD) population. Declining renal function itself represents a continuum of cardiovascular risk and in those individuals who survive to reach ESRD, the risk of suffering a cardiac event is uncomfortably and unacceptably high. Pro-thrombotic status may contribute to this increased risk. Global thrombotic status assessment, including measurement of occlusion time (OT) the time taken to form an occlusive platelet rich thrombus and thrombolytic status (time taken to lyse such thrombus) as assessed by measuring Lysis Time (LT), may identify vulnerable patients. The aim of this study was to assess overall thrombotic status in ESRD and relate this to cardiovascular and peripheral thrombotic risk. Small sub studies were also planned to establish the effect of RRT modality on the thrombotic status.

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