Deficiency in apoptosis-inducing factor recapitulates chronic kidney disease via aberrant mitochondrial homeostasis

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein with dual roles in redox signaling and programmed cell death. Deficiency in AIF is known to result in defective oxidative phosphorylation (OXPHOS), via loss of complex I activity and assembly in other tissues. Because the kidney relies on OXPHOS for metabolic homeostasis, we hypothesized that a decrease in AIF would result in chronic kidney disease (CKD). Here, we report that partial knockdown of Aif in mice recapitulates many features of CKD, in association with a compensatory increase in the mitochondrial ATP pool via a shift toward mitochondrial fusion, excess mitochondrial reactive oxygen species production, and Nox4 upregulation. However, despite a 50% lower AIF protein content in the kidney cortex, there was no loss of complex I activity or assembly. When diabetes was superimposed onto Aif knockdown, there were extensive changes in mitochondrial function and networking, which augmented the renal lesion. Studies in patients with diabetic nephropathy showed a decrease in AIF within the renal tubular compartment and lower AIFM1 renal cortical gene expression, which correlated with declining glomerular filtration rate. Lentiviral overexpression of Aif1m rescued glucose-induced disruption of mitochondrial respiration in human primary proximal tubule cells. These studies demonstrate that AIF deficiency is a risk factor for the development of diabetic kidney disease.

The role of religion and spirituality in coping with kidney disease and haemodialysis in Thailand

BACKGROUND: People with chronic kidney disease (CKD) face various problems including psychological, socioeconomic and physical effects associated with CKD and its treatment. They need to develop strategies to help them cope with CKD and life challenges. Religion and spirituality are important coping strategies, but their role in helping people cope with CKD and haemodialysis (HD) in Thailand is relatively unknown.

AIMS: To investigate the role of religion and spirituality in coping with CKD and its treatment in Thailand.

DESIGN: An exploratory, qualitative approach was undertaken using semistructured individual interviews.
METHOD: Purposive sampling was used to recruit participants. Face-to-face, in-depth individual interviews using open questions were conducted during January and February 2012. Interviews were audio-recorded and transcribed verbatim. Data were analysed using the framework method of qualitative data analysis.

FINDINGS: Twenty people receiving HD participated: age range 23-77 years, mean 53.7 (±16.38 SD). Ten were women. Participants reported use of religious and spiritual practices to cope with CKD and its treatment, including religious and spiritual explanations for developing CKD, karmic disease, making merit, reading Dharma books, praying and chanting to save life and making a vow to Pran-Boon.

CONCLUSION: Religion and spirituality provide powerful coping strategies that can help Thai people with CKD overcome the associated distress and difficulties. Religion and spirituality cannot be separated in Thai culture because Thai people are both religious and spiritual.

Peridontal disease : the overlooked diabetes complication

Periodontal diseases are infectious processes that occur in the presence of bacteria, which trigger an inflammatory response. Periodontal disease is associated with many medical conditions, including diabetes mellitus and its complications (such as kidney disease). It has been described as the "sixth diabetes complication" but is often overlooked in routine diabetes management and complication screening processes. Proactive, preventative dental and diabetes self care, as well as regular dental and diabetes assessment, are important management strategies because periodontal disease contributes to the progression of impaired glucose tolerance to diabetes mellitus and to hyperglycemia in individuals with established diabetes.

Barriers to kidney transplants in Indonesia : a literature review

Background: People living with chronic kidney disease will require renal dialysis or a kidney transplant to maintain life. Although Indonesia has a developing healthcare industry, Indonesia's kidney transplant rates are lower than comparable nations.

Purpose: To explore the healthcare literature to identify barriers to kidney transplants in particular in relation to Indonesia.

Methods: Healthcare databases were searched (CINAHL, Medline, EBSCOhostEJS, Blackwell Synergy, Web of Science, PubMed, Google Scholar and Proquest 5000) using the search terms: transplant, kidney disease, renal, dialysis, haemodialysis, Indonesia and nursing. The search was limited to English and Indonesian language data sources from 1997 to 2007. Reference lists of salient academic articles were hand searched.

Results: The results of our search identified six articles that met our criteria. Costs are the major barrier to kidney transplant in Indonesia, followed by cultural beliefs, perception of the law, lack of information and lack of infrastructure. In addition, kidney disease prevention strategies are required.

Conclusions: There are many complex socio-economic, geographical, legal, cultural and religious factors that contribute to low kidney transplant rates in Indonesia. Although an increase in transplantation rates will require strategies from various agencies, healthcare professionals, including nurses, can play a role in overcoming some barriers. Community education programmes, improving their own education levels and by increasing empowerment in nursing we may contribute to improved kidney transplant rates in Indonesia.

Estimating individual glomerular volume in the human kidney : clinical perspectives

Background. Measurement of individual glomerular volumes (IGV) has allowed the identification of drivers of glomerular hypertrophy in subjects without overt renal pathology. This study aims to highlight the relevance of IGV measurements with possible clinical implications and determine how many profiles must be measured in order to achieve stable size distribution estimates.

Methods. We re-analysed 2250 IGV estimates obtained using the disector/Cavalieri method in 41 African and 34 Caucasian Americans. Pooled IGV analysis of mean and variance was conducted. Monte-Carlo (Jackknife) simulations determined the effect of the number of sampled glomeruli on mean IGV. Lin’s concordance coefficient (RC), coefficient of variation (CV) and coefficient of error (CE) measured reliability.

Results. IGV mean and variance increased with overweight and hypertensive status. Superficial glomeruli were significantly smaller than juxtamedullary glomeruli in all subjects (P < 0.01), by race (P < 0.05) and in obese individuals (P < 0.01). Subjects with multiple chronic kidney disease (CKD) comorbidities showed significant increases in IGV mean and variability. Overall, mean IGV was particularly reliable with nine or more sampled glomeruli (RC > 0.95, <5% difference in CV and CE). These observations were not affected by a reduced sample size and did not disrupt the inverse linear correlation between mean IGV and estimated total glomerular number.

Conclusions. Multiple comorbidities for CKD are associated with increased IGV mean and variance within subjects, including overweight, obesity and hypertension. Zonal selection and the number of sampled glomeruli do not represent drawbacks for future longitudinal biopsy-based studies of glomerular size and distribution.

Medicine non-adherence in kidney transplantation

Background: The increasing prevalence of chronic kidney disease, the relative shortage of kidney donors and the economic- and health-related costs of kidney transplant rejection make the prevention of adverse outcomes following transplantation a healthcare imperative. Although strict adherence to immunosuppressant medicine regimens is key to preventing kidney rejection, evidence suggests that adherence is sub-optimal. Strategies need to be developed to help recipients of kidney transplants adhere to their prescribed medicines. Findings: This review has found that a number of factors contribute to poor adherence, for example, attitudes towards medicine taking and forgetfulness. Few investigations have been conducted, however, on strategies to enhance medicine adherence in kidney transplant recipients. Strategies that may improve adherence include pharmacist-led interventions (incorporating counselling, medicine reviews and nephrologist liaison) and nurse-led interventions (involving collaboratively working with recipients to understand their routines and offering solutions to improve adherence). Strategies that have shown to have limited effectiveness include supplying medicines free of charge and providing feedback on a participant's medicine adherence without any educational or behavioural interventions. Conclusion: Transplantation is the preferred treatment option for people with end-stage kidney disease. Medicine non-adherence in kidney transplantation increases the risk of rejection, kidney loss and costly treatments. Interventions are needed to help the transplant recipient take all their medicines as prescribed to improve general well-being, medicine safety and reduce healthcare costs. © 2014 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013

Background: Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65·3 years (UI 65·0-65·6) in 1990, to 71·5 years (UI 71·0-71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8-48·2) to 54·9 million (UI 53·6-56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased.For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.

Microvascular disease after renal transplantation

Background/Aims: Individuals who reach end-stage kidney disease (CKD5) have a high risk of vascular events that persists even after renal transplantation. This study compared the prevalence and severity of microvascular disease in transplant recipients and patients with CKD5. Methods: Individuals with a renal transplant or CKD5 were recruited consecutively from renal clinics, and underwent bilateral retinal photography (Canon CR5-45, Canon). Their retinal images were deidentified and reviewed for hypertensive/microvascular signs by an ophthalmologist and a trained grader (Wong and Mitchell classification), and for vessel caliber at a grading centre using a computer-assisted method and Knudtson’s modification of the Parr-Hubbard formula. Results: Ninety-two transplant recipients (median duration 6.4 years, range 0.8 to 28.8) and 70 subjects with CKD5 were studied. Transplant recipients were younger (p<0.001), with a higher eGFR (p< 0.001), but were just as likely to have a moderate-severe hypertensive/microvascular retinopathy (46/92, 50%) as subjects with CKD5 (38/70, 54%; OR 0.84, CI 0.45 to 1.57, p=0.64), and had similar mean arteriole and venular calibres (135.1 ± 7.5 μm and 137.9 ± 14.9 μm, p=0.12; and 199.1 ± 17.8 μm and 202.4 ± 27.8 μm, p=0.36, respectively). Arteriole and venular caliber were not different in nine patients examined before and after transplantation (p=0.62 and p=0.11, respectively). Conclusions: Hypertensive/microvascular disease occurred just as often and was generally as severe in transplant recipients and subjects with CKD5. Microvascular disease potentially contributes to increased cardiac events post- transplantation.

The transplant team's support of kidney transplant recipients to take their prescribed medications: a collective responsibility.

AIMS AND OBJECTIVES: To obtain an understanding of how health professionals support the kidney transplant patient to take their medications as prescribed long term. BACKGROUND: Kidney transplantation requires stringent adherence to complex medication regimens to prevent graft rejection and to maintain general well-being. Medication nonadherence is common in kidney transplantation, emerging in the first few months post-transplantation, leading to poor patient outcomes. DESIGN: Exploratory qualitative design. METHODS: Five focus groups were conducted with a total of seven renal nurse transplant coordinators, two renal transplant nurse unit managers, seven nephrologists, seven pharmacists, four social workers, and one consumer representative representing all five hospitals offering adult kidney transplantation in Victoria, Australia in 2014. The views of two general practitioners who were unable to attend the focus groups were incorporated into the data set. All data underwent thematic analysis. RESULTS: Analysis revealed that adherence was a collective responsibility involving the whole of the transplant team and the patient via education blitz in hospital, identifying and managing nonadherence, promotion of self-advocacy, and the partnership between the patient and health professional. Patients were directed how to take their complex medications to be self-empowered, yet the partnership between the patient and health professional limited the patient's voice. CONCLUSION: Although medication adherence was a collective responsibility, communication was often one-way chiefly as a result of staffing and time constraints, hindering effective partnerships necessary for medication adherence. Expert skills in communication and adherence counselling are necessary to identify barriers affecting medication adherence. Patients need to be systematically screened, prepared and supported long-term within an accommodating healthcare system for the reality of caring for their transplanted kidney. RELEVANCE TO CLINICAL PRACTICE: Kidney transplant recipients require systematic preparation and quality long-term follow-up to adhere to their prescribed medications.

The effect of holiday haemodialysis treatments on patient mood, adverse symptoms and subjective wellbeing using the Big Red Kidney Bus

BACKGROUND AND AIMS: People with end-stage kidney disease receiving haemodialysis are restricted to holidays where dialysis services are readily available. Holiday dialysis in regional, rural and remote areas is particularly challenging. The aims of this study were to (1) evaluate the wellbeing of those who received dialysis in a holiday haemodialysis bus, and (2) to measure patient wellbeing with that of a comparable cohort of haemodialysis patients. METHODS: A three machine haemodialysis bus, the Big Red Kidney Bus, was built to enable people, their families and carers to take holidays across a range of tourist destinations in Victoria, Australia. Measures included pre-post subjective wellbeing, dialysis symptoms and mood questionnaires complemented by post semi-structured telephone interviews. RESULTS: Participating holidaymakers were positive about the haemodialysis bus service and the standard of care experienced. They reported decreased dialysis side effects of fatigue, muscle cramp, and dry skin. The overall number of reported symptoms decreased and the perceived level of bother associated with symptoms also decreased. No changes in subjective wellbeing and mood were detected. Mean Personal Wellbeing Index scores were significantly higher than in a comparative haemodialysis sample. CONCLUSION: The Big Red Kidney Bus provided a safe and feasible holiday dialysis service. Holidaymakers' wellbeing was reflected by the decreased dialysis patient side effects.

Expanding evidence for the multiple dangers of epidemic abdominal obesity

The waistline of America has been expanding now for decades,1 largely as a consequence of an obesogenic environment, with a car-worshipping culture and take-away lifestyle par excellence.2 No upper limit to the prevalence or extent of obesity is yet apparent, and many countries and communities worldwide are busily following the American lead. Accumulating research evidence suggests that the personal and economic costs of the obesity epidemic are immense,3 driven by the obesity-related increases in risk for conditions such as type 2 diabetes mellitus, the metabolic syndrome, cardiovascular disease (CVD), kidney disease, arthritis, cancer, asthma, and sleep-disordered breathing. In addition, decreases are apparent in self-esteem and quality of life.

Dialysis residential care : a future dialysis service model

People with chronic kidney disease are ageing and have increasing co-morbidities. The current delivery of renal replacement therapy, dialysis and transplantation, needs to adjust to changing patient needs. This paper proposes a potential future service delivery model featuring a dialysis residential care facility and a care coordination focus. The residential care facility would be composed of four levels of care; high, hostel, independent and outpatient. The paper argues that this model may result in decreased morbidity, improved patient quality of life and may prove cost effective. Patients' nutritional status, medication adherence and transport efficiency may be improved. We propose this model to stimulate further debate in order to meet the needs of current and future chronic kidney disease patients.

Being a parent on dialysis : a literature review

Aim
This literature review explored the extant literature to further our understanding of the experience of being a parent on dialysis.
Methods
Keywords used to search the literature were haemodialysis, hemodialysis, chronic kidney disease, end stage renal disease, parent and experience. Databases searched included CINAHL, Medline, Wiley/Blackwell, EBSCOHost, Web of Science, Pubmed, and ProQuest. Years included were 1999 to 2009. Seventeen primary research articles (sixteen qualitative, one mixed methods) met the search criteria with only one on parents undergoing dialysis.
Findings
The experience of the parent on dialysis has rarely been explored in the literature. Related research has indicated important themes including: restricted lives; relationships; adjustment; consequences and future outlook.
Conclusions
More should be known about challenges that face parents who receive dialysis. This review established an urgent need for further research to determine the experiences and needs of this population to provide empirical, person-centred nursing care.

Is point of care testing for anaemia (HB) and microalbumin feasible in people with type 2 diabetes attending diabetes outpatient clinics?

Introduction: Diabetes is the major cause of chronic kidney disease (CKD) in Australia. Anaemia of CKD occurs earlier than in non-diabetics and is often insidious and undetected.

Aim: A large, prospective, single-centre study was undertaken to determine the feasibility of point of care testing (POCT) haemoglobin (Hb) and microalbumin in people with type 2 diabetes (T2DM) attending routine outpatient clinic appointments (OPC).

Method: Clinic nurses measured Hb and microalbumin using the HemoCue Haemoglobin Capillary Analyser and the HemoCue Urine Albumin Analyser (Medipac Scientific), respectively when they tested blood glucose, weight and blood pressure. The nurses were trained to use the analysers before the study commenced. Standard demographic data, duration of diabetes, treatment mode, and presence of complications, comorbidities, and HbA1c were ascertained from patients’ medical records.

Results: Five hundred and fifty-four (80%) patients were screened. The nurses were able to perform the tests competently but testing, especially microalbumin, was time-consuming. Patients’ mean age was 62 years (11 SD): 230 females, mean blood glucose (BG) 10 (3.9 SD) mmol/L, mean haemoglobin 127.2 (16.3 SD) g/L; mean microalbumin 47.8 (58.7 SD) mg/L: 324 were males, mean BG 10.2 (3.9 SD) mmol/L, mean Hb 138.6 (18.8 SD) gm/L, and mean microalbumin 67.9 (73.9 SD) mg/L. 27% of males and 22% of females were anaemic. Of those with anaemia, 27% of females and 29% of males had microalbuminuria.

Conclusions: POCT is feasible in routine outpatient clinics but is time-consuming. One in four T2DM attending OPC were anaemic. POCT Hb testing in OPC is feasible and could identify T2DM who need full haematological assessment.

A combined strength and balance exercise program to decrease falls risk in dialysis patients : a feasibility study

People suffering end-stage kidney disease receiving hemodialysis have a greater risk of falling and suffering debilitating injuries. The purpose of this study was to examine the feasibility and impact of a combined strength and balance exercise intervention on falls risk in hemodialysis patients. Twenty-four adults (mean age = 67.8 yrs) from two Australian outpatient hemodialysis clinics completed the intervention. Falls risk was measured using the Physiological Profile Assessment (PPA). There was a significant reduction in the median overall falls risk z-score from 1.67 to .52 (z = -3.11, P<.008; r = .45). Median reaction time improved from .30 to .26 sec (z = -2.86, P<.008; r = .41). A strength and balance intervention to reduce the falls risk for dialysis patients is feasible and may reduce falls risk for at risk patients.