The Effect of ß-Glucan Prebiotic on Kidney Function, Uremic Toxins and Gut Microbiome in Stage 3 to 5 Chronic Kidney Disease (CKD) Predialysis Participants: A Randomized Controlled Trial.

There is growing evidence that gut dysbiosis contributes to the progression of chronic kidney disease (CKD) owing to several mechanisms, including microbiota-derived uremic toxins, diet and immune-mediated factors. The aim of this study was to investigate the effect of a ß-glucan prebiotic on kidney function, uremic toxins and the gut microbiome in stage 3 to 5 CKD participants. Fifty-nine participants were randomized to either the ß-glucan prebiotic intervention group (n = 30) or the control group (n = 29). The primary outcomes were to assess kidney function (urea, creatinine and glomerular filtration rate), plasma levels of total and free levels of uremic toxins (p-cresyl sulfate (pCS), indoxyl-sulfate (IxS), p-cresyl glucuronide (pCG) and indoxyl 3-acetic acid (IAA) and gut microbiota using 16S rRNA sequencing at baseline, week 8 and week 14. The intervention group (age 40.6 ± 11.4 y) and the control group (age 41.3 ± 12.0 y) did not differ in age or any other socio-demographic variables at baseline. There were no significant changes in kidney function over 14 weeks. There was a significant reduction in uremic toxin levels at different time points, in free IxS at 8 weeks (p = 0.003) and 14 weeks (p < 0.001), free pCS (p = 0.006) at 14 weeks and total and free pCG (p < 0.001, p < 0.001, respectively) and at 14 weeks. There were no differences in relative abundances of genera between groups. Enterotyping revealed that the population consisted of only two of the four enterotypes: Bacteroides 2 and Prevotella. The redundancy analysis showed a few factors significantly affected the gut microbiome: these included triglyceride levels (p < 0.001), body mass index (p = 0.002), high- density lipoprotein (p < 0.001) and the prebiotic intervention (p = 0.002). The ß-glucan prebiotic significantly altered uremic toxin levels of intestinal origin and favorably affected the gut microbiome.

Living with someone else's penis: The lived experiences of two South African penile allograft recipients: A descriptive phenomenological study.

BACKGROUND: In South Africa, penile loss is a recognised complication of ritual circumcision which has a profoundly negative effect on these men's psyches and their everyday lives. The purpose of this paper was to investigate the experiences of the first two South African penile allograft transplantation recipients in order to assess the psychosocial impact of this surgery. MATERIALS AND METHODS: A qualitative descriptive phenomenology approach was used. A total of four in-depth interviews were conducted with the two South African penile transplant recipients. The interviews were transcribed verbatim while adding the field and observational notes. Thematic analysis was used to derive meaning from the collected data. RESULTS: After the penile loss, both participants reported feeling suicidal for the following reasons: their communities shunned them and regarded them as 'dead,' they felt severely ashamed of their disfigured bodies, they were unable to develop intimate relationships and could not have children. Transplantation gave them a fully functional penis, which resolved the majority of these issues. The participants were able to build relationships and satisfy their own and their partners' sexual and relationship needs. The transplant led to complete restoration of their self-image and manhood. They were, however, still persecuted by their traditional communities as they had not successfully completed the ritual circumcision ceremony. CONCLUSION: This study emphasises the necessity of offering penile transplantation as treatment for penile loss as this is not only life enhancing but lifesaving, especially within the South African context.

Considerations on equity in management of end-stage kidney disease in low- and middle-income countries.

Achievement of equity in health requires development of a health system in which everyone has a fair opportunity to attain their full health potential. The current, large country-level variation in the reported incidence and prevalence of treated end-stage kidney disease indicates the existence of system-level inequities. Equitable implementation of kidney replacement therapy (KRT) programs must address issues of availability, affordability, and acceptability. The major structural factors that impact equity in KRT in different countries are the organization of health systems, overall health care spending, funding and delivery models, and nature of KRT prioritization (transplantation, hemodialysis or peritoneal dialysis, and conservative care). Implementation of KRT programs has the potential to exacerbate inequity unless equity is deliberately addressed. In this review, we summarize discussions on equitable provision of KRT in low- and middle-income countries and suggest areas for future research.

Developing the ethical framework of end-stage kidney disease care: from practice to policy.

Ethical issues relating to end-stage kidney disease (ESKD) care are increasingly being discussed by clinicians and ethicists but are still infrequently considered at a policy level or in the education and training of health care professionals. In most lower-income countries, access to kidney replacement therapies such as dialysis is not universal, leading to overt or implicit rationing of resources and potential exclusion from care of those who are unable to sustain out-of-pocket payments. These circumstances create significant inequities in access to ESKD care within and between countries and impose emotional and moral burdens on patients, families, and health care workers involved in decision-making and provision of care. End-of-life decision-making in the context of ESKD care in all countries may also create ethical dilemmas for policy makers, professionals, patients, and their families. This review outlines several ethical implications of the complex challenges that arise in the management of ESKD care around the world. We argue that more work is required to develop the ethics of ESKD care, so as to provide ethical guidance in decision-making and education and training for professionals that will support ethical practice in delivery of ESKD care. We briefly review steps that may be required to accomplish this goal, discussing potential barriers and strategies for success.

Pattern of renal amyloidosis in South Africa.

BACKGROUND: Kidney disease is a serious manifestation of systemic amyloidosis and a major cause of morbidity and mortality. Tuberculosis (TB) occurs up to 27 times more commonly in human immunodeficiency virus (HIV) infected patients and is also an important cause of renal amyloid; there are however no reports of renal amyloidosis in South Africa in the HIV era. METHODS: This was a retrospective record review of cases of amyloidosis diagnosed on renal biopsies at our tertiary referral hospital between January 1985 and December 2016. RESULTS: Forty-six cases of amyloidosis were identified over the study period. The calculated biopsy prevalence was 1.38 per 100 non-transplant renal biopsies (95% Confidence Interval 1.02-1.86). AL amyloidosis was identified in 26 (57%) cases and AA in 20 (43%). The median age at presentation was 51 years and 52% of cases were female. Patients with AA amyloidosis were significantly younger compared to their AL counterparts (age 42 years vs. 58 years, p = < 0.001) and were all significantly non-white. The main clinical presentation was nephrotic syndrome (85%) and 52% of cases also had a serum creatinine value of greater than 120 µmol/L. Of the 20 cases of AA amyloidosis, 12 (60%) were associated with tuberculosis. HIV infection was noted in only two (10%) of the 20 AA cases. Median survival after diagnosis was 2 months. CONCLUSION: Amyloidosis is a rare cause of kidney disease and typically presents with nephrotic syndrome. A similar number of AA and AL types were observed, and outcomes are worse in cases of AA amyloid. While TB remains the major underlying disease in this type, HIV infection was infrequent in cases of AA renal amyloidosis.

Increasing access to integrated ESKD care as part of universal health coverage.

The global nephrology community recognizes the need for a cohesive strategy to address the growing problem of end-stage kidney disease (ESKD). In March 2018, the International Society of Nephrology hosted a summit on integrated ESKD care, including 92 individuals from around the globe with diverse expertise and professional backgrounds. The attendees were from 41 countries, including 16 participants from 11 low- and lower-middle-income countries. The purpose was to develop a strategic plan to improve worldwide access to integrated ESKD care, by identifying and prioritizing key activities across 8 themes: (i) estimates of ESKD burden and treatment coverage, (ii) advocacy, (iii) education and training/workforce, (iv) financing/funding models, (v) ethics, (vi) dialysis, (vii) transplantation, and (viii) conservative care. Action plans with prioritized lists of goals, activities, and key deliverables, and an overarching performance framework were developed for each theme. Examples of these key deliverables include improved data availability, integration of core registry measures and analysis to inform development of health care policy; a framework for advocacy; improved and continued stakeholder engagement; improved workforce training; equitable, efficient, and cost-effective funding models; greater understanding and greater application of ethical principles in practice and policy; definition and application of standards for safe and sustainable dialysis treatment and a set of measurable quality parameters; and integration of dialysis, transplantation, and comprehensive conservative care as ESKD treatment options within the context of overall health priorities. Intended users of the action plans include clinicians, patients and their families, scientists, industry partners, government decision makers, and advocacy organizations. Implementation of this integrated and comprehensive plan is intended to improve quality and access to care and thereby reduce serious health-related suffering of adults and children affected by ESKD worldwide.

Correction: Use of the 'Accountability for Reasonableness' Approach to Improve Fairness in Accessing Dialysis in a Middle-Income Country.

[This corrects the article DOI: 10.1371/journal.pone.0164201.].

Use of the 'Accountability for Reasonableness' Approach to Improve Fairness in Accessing Dialysis in a Middle-Income Country.

Universal access to renal replacement therapy is beyond the economic capability of most low and middle-income countries due to large patient numbers and the high recurrent cost of treating end stage kidney disease. In countries where limited access is available, no systems exist that allow for optimal use of the scarce dialysis facilities. We previously reported that using national guidelines to select patients for renal replacement therapy resulted in biased allocation. We reengineered selection guidelines using the 'Accountability for Reasonableness' (procedural fairness) framework in collaboration with relevant stakeholders, applying these in a novel way to categorize and prioritize patients in a unique hierarchical fashion. The guidelines were primarily premised on patients being transplantable. We examined whether the revised guidelines enhanced fairness of dialysis resource allocation. This is a descriptive study of 1101 end stage kidney failure patients presenting to a tertiary renal unit in a middle-income country, evaluated for dialysis treatment over a seven-year period. The Assessment Committee used the accountability for reasonableness-based guidelines to allocate patients to one of three assessment groups. Category 1 patients were guaranteed renal replacement therapy, Category 3 patients were palliated, and Category 2 were offered treatment if resources allowed. Only 25.2% of all end stage kidney disease patients assessed were accepted for renal replacement treatment. The majority of patients (48%) were allocated to Category 2. Of 134 Category 1 patients, 98% were accepted for treatment while 438 (99.5%) Category 3 patients were excluded. Compared with those palliated, patients accepted for dialysis treatment were almost 10 years younger, employed, married with children and not diabetic. Compared with our previous selection process our current method of priority setting based on procedural fairness arguably resulted in more equitable allocation of treatment but, more importantly, it is a model that is morally, legally and ethically more defensible.

An effective approach to chronic kidney disease in South Africa.

Very few patients with end-stage kidney disease in South Africa receive renal replacement treatment (RRT), despite the rapidly growing demand, because of resource constraints. Nephrologists who agonise daily about who to treat and who not to, and have been doing so since the inception of dialysis in this country, welcomed the opportunity to interact with the National Department of Health at a recent summit of stakeholders. The major challenges were identified and recommendations for short- to long-term solutions were made. While the renal community can still improve efficiencies, it is clear that much of the responsibility for improving access to RRT and reducing inequities must be borne by the national government. The summit marks the first step in a process that we hope will ultimately culminate in universal access to RRT for all South Africans.

Relationship between body mass index and mortality in adults on maintenance hemodialysis: a systematic review.

OBJECTIVE: The primary objective of this systematic review was to determine the relationship between body mass index (BMI) and all-cause and cardiovascular mortality. DESIGN: Systematic review of primarily observational studies. PATIENTS: Adult patients from all gender, race, or ethnic groups on maintenance hemodialysis. METHODS: Medline, Science Citation Index, Academic Search Premier, Cochrane Library, and Embase electronic databases covering the period 1966 to December 2008 were searched with the help of a qualified librarian. Reference lists of included papers and collections also were searched. Each study was reviewed by 2 independent reviewers who also performed the data extraction from full papers. Differences between reviewers were resolved by consensus or by a third reviewer in the case of disagreements. The quality of studies selected for inclusion in the systematic review was also assessed by 2 independent reviewers. MAIN OUTCOMES: BMI and mortality. RESULTS: Eighteen studies (60%) reported a significant inverse relationship between all-cause mortality and BMI. This inverse relationship was more prevalent in older patients, larger retrospective studies, and studies that did not adjust for inflammation. On the other hand, 57% of the 7 studies reporting on cardiovascular mortality found no significant relationship with BMI. CONCLUSIONS: This systematic review shows evidence of an inverse relationship between BMI and all-cause mortality in adult patients on maintenance HD, especially in older patients, but the relationship with cardiovascular mortality is less clear.