Increased tubulointerstitial recruitment of human CD141(hi) CLEC9A(+) and CD1c(+) myeloid dendritic cell subsets in renal fibrosis and chronic kidney disease

Dendritic cells (DCs) play critical roles in immune-mediated kidney diseases. Little is known, however, about DC subsets in human chronic kidney disease, with previous studies restricted to a limited set of pathologies and to using immunohistochemical methods. In this study, we developed novel protocols for extracting renal DC subsets from diseased human kidneys and identified, enumerated, and phenotyped them by multicolor flow cytometry. We detected significantly greater numbers of total DCs as well as CD141(hi) and CD1c(+) myeloid DC (mDCs) subsets in diseased biopsies with interstitial fibrosis than diseased biopsies without fibrosis or healthy kidney tissue. In contrast, plasmacytoid DC numbers were significantly higher in the fibrotic group compared with healthy tissue only. Numbers of all DC subsets correlated with loss of kidney function, recorded as estimated glomerular filtration rate. CD141(hi) DCs expressed C-type lectin domain family 9 member A (CLEC9A), whereas the majority of CD1c(+) DCs lacked the expression of CD1a and DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), suggesting these mDC subsets may be circulating CD141(hi) and CD1c(+) blood DCs infiltrating kidney tissue. Our analysis revealed CLEC9A(+) and CD1c(+) cells were restricted to the tubulointerstitium. Notably, DC expression of the costimulatory and maturation molecule CD86 was significantly increased in both diseased cohorts compared with healthy tissue. Transforming growth factor-β levels in dissociated tissue supernatants were significantly elevated in diseased biopsies with fibrosis compared with nonfibrotic biopsies, with mDCs identified as a major source of this profibrotic cytokine. Collectively, our data indicate that activated mDC subsets, likely recruited into the tubulointerstitium, are positioned to play a role in the development of fibrosis and, thus, progression to chronic kidney disease.

Adherence to fish oil intervention in patients with chronic kidney disease

Objective: With growing recognition of the role of inflammation in the development of chronic and acute disease, fish oil is increasingly used as a therapeutic agent, but the nature of the intervention may pose barriers to adherence in clinical populations. Our objective was to investigate the feasibility of using a fish oil supplement in hemodialysis patients. ---------- Design: This was a nonrandomized intervention study.---------- Setting: Eligible patients were recruited at the Hemodialysis Unit of Wesley Hospital, Brisbane, Queensland, Australia. Patients The sample included 28 maintenance hemodialysis patients out of 43 eligible patients in the unit. Exclusion criteria included patients regularly taking a fish oil supplement at baseline, receiving hemodialysis for less than 3 months, or being unable to give informed consent.---------- Intervention: Eicosapentaenoic acid (EPA) was administered at 2000 mg/day (4 capsules) for 12 weeks. Adherence was measured at baseline and weekly throughout the study according to changes in plasma EPA, and was further measured subjectively by self-report.---------- Results: Twenty patients (74%) adhered to the prescription based on changes in plasma EPA, whereas an additional two patients self-reported good adherence. There was a positive relationship between fish oil intake and change in plasma EPA. Most patients did not report problems with taking the fish oil. Using the baseline data, it was not possible to characterize adherent patients.---------- Conclusions: Despite potential barriers, including the need to take a large number of prescribed medications already, 74% of hemodialysis patients adhered to the intervention. This study demonstrated the feasibility of using fish oil in a clinical population.

Compliance, peritoneal dialysis and chronic kidney disease : lessons from the literature

Poor patient compliance with peritoneal dialysis (PD) has significant adverse effects on morbidity and mortality rates in individuals with chronic kidney disease (CKD). It also adds to the resource burdens of healthcare services and providers. This paper explores the notion of PD compliance in patients with CKD with reference to the relevant published literature. The analysis of the literature reveals that ‘PD compliance’ is a complex and challenging construct for both patients and health professionals. There is no universal definition of compliance that is widely adopted in practice and research, and therefore a lack of consensus on how to determine ‘compliant’ patient outcomes. There are also multiple and interconnected determinants of PD compliance that are context-bound, which healthcare professionals must be aware of, and which makes producing consensus of measuring PD compliance difficult. The complexity of the interventions required to produce even a modest improvement in PD compliance, which are described in this paper, are significant. Compliance with PD and other treatments for CKD is a multidimensional, context-bound concept, that to date has tended to efface the role and needs of the renal patient. We conclude the paper with the implications for contemporary practice.

A longitudinal study of health-related quality of life, fatigue and physical activity in chronic kidney disease patients

This study assessed the health-related quality of life (HRQoL), fatigue and physical activity levels of 28 persons with chronic kidney disease (CKD) on initial administration of an erythropoietin stimulating agent, and at 3 months, 6 months and 12 months. The sample comprised of 15 females and 13 males whose ages ranged from 31 to 84 years. Physical activity was measured using the Human Activity Profile (HAP): Self-care, Personal/Household work, Entertainment/Social, Independent exercise. Quality of life was measured using the SF-36 which gives scores on physical health (physical functioning, role-physical, bodily pain and general health) and mental health (vitality, social functioning, role-emotional and emotional well-being). Fatigue was measured by the Fatigue Severity Scale (FSS). Across all time points the renal sample engaged in considerably less HAP personal/household work activities and entertainment/social activities compared to healthy adults. The normative sample engaged in three times more independent/exercise activities compared to renal patients. One-way Repeated measures ANOVAs indicated a significant change over time for SF-36 scales of role physical, vitality, emotional well-being and overall mental health. There was a significant difference in fatigue levels over time [F(3,11) = 3.78, p<.05]. Fatigue was highest at baseline and lowest at 6 months. The more breathlessness the CKD patient reported, the fewer activities undertaken and the greater the reported level of fatigue. There were no significant age differences over time for fatigue or physical activity. Age differences were only found for SF-36 mental health at 3 months (t=-2.41, df=14, p<.05). Those younger than 65 years had lower emotional well-being compared to those aged over 65. Males had poorer physical health compared to females at 12 months. There were no significant gender differences on mental health at any time point. In the management of chronic kidney disease, early detection of a person’s inability to engage in routine activities due to fatigue is necessary. Early detection would enable timely interventions to optimise HRQoL and independent exercise.

Symptom burden in chronic kidney disease : a review of recent literature

Background: People living with chronic kidney disease (CKD) experience multiple symptoms due to both the disease and its treatment, these symptoms are often under recognized. The majority of studies have focused on an individual symptom; however these symptoms rarely occur in isolation and may instead occur in clusters. Aim of review: This review investigated the total symptom burden in advanced CKD (stages 4 and 5) and identified the key instruments that are used to assess multiple symptoms. Methods: A literature search from 2006 to 2012 was undertaken and a total of 19 articles were included. Result: The most common CKD symptoms were fatigue or lack of energy, feeling drowsy, pain and pruritus. However, symptom assessment instruments varied between studies, often with inconsistent or inadequate symptom dimensions. Conclusion: People with CKD experience a high burden of symptom, although little is known about the burden for people with CKD stage 4 and for those with CKD stage 5 receiving PD. This review recommends that a full range of symptoms be assessed for those at different stages of CKD. Improved understanding of the burden of symptoms could be used as the basis for treatment choices and for identifying priorities which are likely to contribute to a better quality of life and improve the quality of care.

Quality of life, fatigue and activity in Australians with chronic kidney disease : a longitudinal study

Aims and objectives This study sought to determine the relationship between health related quality of life (HRQoL), fatigue and activity levels of people with anaemia secondary to chronic kidney disease (CKD) over a 12 month period following the introduction of an erythropoietin stimulating agent (ESA). Background CKD occurs in five stages and it is a complex chronic illness which severely impacts on an individual’s HRQoL, and ability to perform everyday activities. Fatigue is also a common symptom experienced by people with CKD. Design and methods Using a longitudinal repeated measures design, 28 people with CKD completed the SF-36, human activity profile and fatigue severity scale at the commencement of an ESA and then at 3, 6 and 12 months. Results Over a 12 month period, people reported a significant change in HRQoL in relation to role physical, vitality, mental health/emotional well-being and overall mental health. However activity levels did not significantly improve during that time. Both the amount of breathlessness and level of fatigue were highest at baseline and declined over time. Both fatigue and breathlessness were correlated with less reported general health over time. Conclusion Renal nurses, in dialysis units and CKD outpatient clinics, have repeated and frequent contact with people with CKD over long periods of time, and are in an ideal position to routinely assess fatigue and activity levels and to institute timely interventions. Early detection would enable timely nursing interventions to optimise HRQoL and independent activity. Relevance to Clinical Practice Drawing on rehabilitation nursing interventions could assist renal nurses to minimize the burden of fatigue and its impact on simple everyday activities and a person’s quality of life. These interventions are important for people who are living at home and could assist in lowering the burden on home support services.

Self-management programs in stage 1-4 chronic kidney disease : a literature review.

Background Chronic kidney disease (CKD) is a complex health problem, which requires individuals to invest considerable time and energy in managing their health and adhering to multifaceted treatment regimens. Objectives To review studies delivering self-management interventions to people with CKD (Stages 1–4) and assess whether these interventions improve patient outcomes. Design: Systematic review. Methods Nine electronic databases (MedLine, CINAHL, EMBASE, ProQuest Health & Medical Complete, ProQuest Nursing & Allied Health, The Cochrane Library, The Joanna Briggs Institute EBP Database, Web of Science and PsycINFO) were searched using relevant terms for papers published between January 2003 and February 2013. Results The search strategy identified 2,051 papers, of which 34 were retrieved in full with only 5 studies involving 274 patients meeting the inclusion criteria. Three studies were randomised controlled trials, a variety of methods were used to measure outcomes, and four studies included a nurse on the self-management intervention team. There was little consistency in the delivery, intensity, duration and format of the self-management programmes. There is some evidence that knowledge- and health-related quality of life improved. Generally, small effects were observed for levels of adherence and progression of CKD according to physiologic measures. Conclusion The effectiveness of self-management programmes in CKD (Stages 1–4) cannot be conclusively ascertained, and further research is required. It is desirable that individuals with CKD are supported to effectively self-manage day-to-day aspects of their health.

Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease

Chronic kidney disease (CKD) in ageing is a burden on health systems worldwide. Rat models of age-related CKD linked with obesity and hypertension were used to investigate alterations in oxidant handling and energy metabolism to identify gene targets or markers for age-related CKD. Young adult (3 months) and old (21–24 months) spontaneously-hypertensive (SHR), normotensive Wistar-Kyoto (WKY) and Wistar rats (normotensive, obese in ageing) were compared for renal functional and physiological parameters, renal fibrosis and inflammation, oxidative stress (hemeoxygenase-1/HO-1), apoptosis and cell injury (including Bax:Bcl-2), phosphorylated and non-phosphorylated forms of oxidant and energy sensing proteins (p66Shc, AMPK), signal transduction proteins (ERK1/2, PKB), and transcription factors (NF-κB, FoxO1). All old rats were normoglycemic. Renal fibrosis, tubular epithelial apoptosis, interstitial macrophages and myofibroblasts (all p < 0.05), p66Shc/phospho-p66 (p < 0.05), Bax/Bcl-2 ratio (p < 0.05) and NF-κB expression (p < 0.01) were highest in old obese Wistars. Expression of phospho-FoxO/FoxO was elevated in old Wistars (p < 0.001) and WKYs (p < 0.01). SHRs had high levels in young and old rats. Expression of PKB, phospho-PKB, ERK1/2 and phospho-ERK1/2 were significantly elevated in all aged animals. These results suggest that obesity and hypertension have differing oxidant handling and signalling pathways that act in the pathogenesis of age-related CKD

The effectiveness of interventions which promote self-management for people with End Stage Renal Disease undergoing haemodialysis

Review Objectives: This systematic review seeks to establish what best practice is for: Interventions which promote self-management for patients with End Stage Renal Disease (ERSD) undergoing Haemodialysis. Review questions: 1) Do education interventions improve self-management for patients with end stage renal disease? 2) Do psychosocial interventions such as Cognitive Behavioural Therapy, behavioural therapy or other counselling therapies and social support, improve self-management for patients with end stage renal disease? Criteria for considering studies for this review: Types of participants: This component of the review will consider studies with: • All adults over the age of 18 years • Patients with end stage renal disease • Undergoing haemodialysis Types of interventions/Phenomena of Interest: All studies evaluating the following interventions will be considered for inclusion in the review such as: Interventions which promote self management including: • Education interventions. • Psychosocial interventions such as cognitive behavioural therapy and other behavioural therapies, counselling and social support. Types of outcome measures/anticipated outcomes: This component of the review will consider studies that include the following outcomes: • Adherence with haemodialysis treatment, • Depression and/or anxiety, • Quality of life, • Carer burnout, • Social support • Patient satisfaction • Adverse events potentially attributable to the intervention or control treatment • Cost effectiveness of home haemodialysis Keywords chronic kidney failure; renal failure; end stage renal disease; chronic kidney disease

Self-management support for people with chronic kidney disease: Patient perspectives

Background Self-management of chronic kidney disease (CKD) is crucial for health outcomes and people need to be effectively supported by healthcare professionals (HCPs). Some programmes designed to improve self-management have been implemented, but people with the disease are rarely consulted regarding what they desire from these programmes. Objectives To provide a synthesis of the literature on preferences for self-management support of people with CKD. Design An integrative review. Methods Four databases (MedLine, CINAHL, PsycARTICLES and PsycINFO) were searched using relevant search terms. Results The search strategy identified 1,913 records, of which 12 studies met inclusion criteria. Ten themes were identified as important areas to be addressed by self-management interventions. In addition, patient suggestions for implementation of such interventions are discussed. Conclusion The principles of a person-centred approach ought to frame the support provided by HCPs when supporting those with CKD to better self-manage.

Which patients with chronic kidney disease have the greatest symptom burden? A comparative study of advanced CKD stage and dialysis modality

Background Chronic kidney disease (CKD) leads to a range of symptoms, which are often under-recognised and little is known about the multidimensional symptom experience in advanced CKD. Objectives To examine (1) symptom burden at CKD stages 4 and 5, and dialysis modalities, and (2) demographic and renal history correlates of symptom burden. Methods Using a cross-sectional design, a convenience sample of 436 people with CKD was recruited from three hospitals. The CKD Symptom Burden Index (CKD-SBI) was used to measure the prevalence, severity, distress and frequency of 32 symptoms. Demographic and renal history data were also collected. Results Of the sample, 75.5 % were receiving dialysis (haemodialysis, n = 287; peritoneal dialysis, n = 42) and 24.5 % were not undergoing dialysis (stage 4, n = 69; stage 5, n = 38). Participants reported an average of 13.01 ± 7.67 symptoms. Fatigue and pain were common and burdensome across all symptom dimensions. While approximately one-third experienced sexual symptoms, when reported these symptoms were frequent, severe and distressing. Haemodialysis, older age and being female were independently associated with greater symptom burden. Conclusions In CKD, symptom burden is better understood when capturing the multidimensional aspects of a range of physical and psychological symptoms. Fatigue, pain and sexual dysfunction are key contributors to symptom burden, and these symptoms are often under-recognised and warrant routine assessment. The CKD-SBI offers a valuable tool for renal clinicians to assess symptom burden, leading to the commencement of timely and appropriate interventions.