Conservative kidney management and kidney supportive care: core components of integrated care for people with kidney failure.

Integrated kidney care requires synergistic linkage between preventative care for people at risk for chronic kidney disease and health services providing care for people with kidney disease, ensuring holistic and coordinated care as people transition between acute and chronic kidney disease and the 3 modalities of kidney failure management: conservative kidney management, transplantation, and dialysis. People with kidney failure have many supportive care needs throughout their illness, regardless of treatment modality. Kidney supportive care is therefore a vital part of this integrated framework, but is nonexistent, poorly developed, and/or poorly integrated with kidney care in many settings, especially in low- and middle-income countries. To address this, the International Society of Nephrology has (i) coordinated the development of consensus definitions of conservative kidney management and kidney supportive care to promote international understanding and awareness of these active treatments; and (ii) identified key considerations for the development and expansion of conservative kidney management and kidney supportive care programs, especially in low resource settings, where access to kidney replacement therapy is restricted or not available. This article presents the definitions for conservative kidney management and kidney supportive care; describes their core components with some illustrative examples to highlight key points; and describes some of the additional considerations for delivering conservative kidney management and kidney supportive care in low resource settings.

Our dementia challenge: arise palliative care.

While many of the maladies of the 20th century are steadily coming under control, the march of neurodegenerative disorders continues largely unchecked. Dementias are an exemplar of such disorders; their incidence and prevalence continue to rise, in large part due to a steadily ageing population worldwide. They represent a group of chronic, progressive and, ultimately, fatal neurodegenerative diseases. Dementia has remained therapeutically recalcitrant. It is not a single disease, and because of that, we cannot expect a single panacea. While primary prevention rightly gains prominence, those with established disease currently require a shift in focus from curative intent towards improved quality of life. Enter palliative care. The sheer number and complexity of needs of patients with dementia, from the physical to the psychosocial and spiritual, necessitates the engagement of a wide range of medical disciplines, nursing and allied health professionals. One of those disciplines, as highlighted in the recent Australian Royal Commission into Aged Care Quality and Safety, is palliative care. This paper shall expand upon that role in the overall context of care for those with dementia.

Temporal changes and risk factors for death from early withdrawal within 12 months of dialysis initiation-a cohort study.

BACKGROUND: Mortality risk is high soon after dialysis initiation in patients with kidney failure, and dialysis withdrawal is a major cause of early mortality, attributed to psychosocial or medical reasons. The temporal trends and risk factors associated with cause-specific early dialysis withdrawal within 12 months of dialysis initiation remain uncertain. METHODS: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the temporal trends and risk factors associated with mortality attributed to early psychosocial and medical withdrawals in incident adult dialysis patients in Australia between 2005 and 2018 using adjusted competing risk analyses. RESULTS: Of 32 274 incident dialysis patients, 3390 (11%) experienced death within 12 months post-dialysis initiation. Of these, 1225 (36%) were attributed to dialysis withdrawal, with 484 (14%) psychosocial withdrawals and 741 (22%) medical withdrawals. These patterns remained unchanged over the past two decades. Factors associated with increased risk of death from early psychosocial and medical withdrawals were older age, dialysis via central venous catheter, late referral and the presence of cerebrovascular disease; obesity and Asian ethnicity were associated with decreased risk. Risk factors associated with early psychosocial withdrawals were underweight and higher socioeconomic status. Presence of peripheral vascular disease, chronic lung disease and cancers were associated with early medical withdrawals. CONCLUSIONS: Death from dialysis withdrawal accounted for >30% of early deaths in kidney failure patients initiated on dialysis and remained unchanged over the past two decades. Several shared risk factors were observed between mortality attributed to early psychosocial and medical withdrawals.

Feasibility, acceptability, and utility of a nurse-led survivorship program for people with metastatic melanoma (MELCARE).

PURPOSE: Immune checkpoint inhibitors (ICIs) and targeted therapy (TT) have improved the survival of people with metastatic melanoma. We assessed the feasibility, acceptability, and utility of a novel model of nurse-led, telehealth-delivered survivorship care (MELCARE) for this survivor group. METHODS: People ≥ 18 years diagnosed with unresectable stage III or stage IV melanoma who were ≥ 6 months post initiation of ICI/TT with a radiological response suggestive of a long-term response to ICI/TT were recruited from a specialist melanoma centre in Australia. All participants received MELCARE, a nurse-led survivorship program involving two telehealth consultations 3 months apart, needs assessment using the Distress Thermometer (DT) and Problem List, and creation of a survivorship care plan. Feasibility, acceptability, and utility were assessed using rates of consent and study completion, time taken to complete each component of MELCARE, the Acceptability of Intervention Measure (AIM), and a customised utility survey. RESULTS: 31/54 (57%) people consented. Participants were male (21, 68%), with a median age of 67 (range: 46-82). Eleven (35%) were receiving/had received ipilimumab and nivolumab and 27 (87%) had ceased treatment. Feasibility was demonstrated with 97% completing MELCARE. Utility was demonstrated on a customised survey and supported by a reduction in the mean DT score (initial: 5.6, SD: 2.9; follow-up: 1.5, SD: 1.2). Acceptability was demonstrated on 3/4 AIM items. CONCLUSION: MELCARE was feasible and acceptable with high levels of utility. However, the consent rate was 57% indicating some people do not require support. Future studies should consider MELCARE's optimal timing, resourcing, and cost-effectiveness.

A Novel Clinical Tool for the Management of Taste Changes in Patients With Chronic Kidney Disease: The Chronic Kidney Disease Taste Plate.

Taste alteration is a common, but poorly understood, symptom in end-stage kidney disease. The pathophysiology of taste alteration is complex; to date, management has been largely empirical. As our understanding of pathophysiology grows so does the evidence base for its management. This article introduces a clinical tool-the CKD Taste Plate-to assist clinicians in directing management to the underlying pathophysiology of taste alterations in chronic kidney disease.

Chronic Kidney Disease-Associated Pruritus: A Review.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP), also known as uraemic pruritus, is a disabling symptom for patients and a challenging condition for clinicians. Despite being common amongst end-stage kidney disease (ESKD) patients, it remains underestimated and underdiagnosed. The exact pathogenesis remains largely elusive, which hampers the synthesis of a definite treatment approach. SUMMARY: Chronic pruritus (lasting 6 weeks or more in duration) is a common and potentially disabling symptom in patients with advanced CKD. A unified hypothesis of pathogenesis has not yet been concluded. Studies have shown changes in the immunochemical milieu of the skin in patients with CKD-aP with several inciting stimuli identified. However, other unrecognized factors are likely to be involved. This article will review the current observations and understanding of the postulated pathogenesis of CKD-aP, as well as the evidence for current management strategies. Key Messages: CKD-aP is a common and troubling symptom amongst ESKD patients that is associated with decreased quality of life and poor prognosis. Its exact pathogenesis, at the time of writing, is not well-understood. A stepwise approach is recommended for management. Systematic reviews show the largest body of evidence was found for the effectiveness of gabapentin. Comparison is needed between newly emerging pharmacological agents such as kappa-opioid receptor agonists and more established agents, such as the gabapentinoids. Finally, renal transplantation should be considered in severe and refractory cases who are suitable transplant candidates as it has shown an excellent outcome in most cases.

Prevalence of Taste Changes and Association with Other Nutrition-Related Symptoms in End-Stage Kidney Disease Patients.

OBJECTIVES: Gastrointestinal symptoms are common in end-stage kidney disease (ESKD) and have been associated with reduced health-related quality of life and malnutrition. The aim of this study is to describe the prevalence of taste changes in an ESKD population and to evaluate whether taste changes are associated with the presence or severity of other nutrition-related symptoms and malnutrition. METHODS: We conducted a retrospective audit of people with ESKD on conservative, nondialysis management or renal replacement therapy who had completed a taste change assessment. Taste change was assessed on a Likert scale from none to overwhelming. Descriptions of taste changes were also collected. Other outcomes included gastrointestinal symptoms collected using the iPOS-renal symptom inventory, nutritional status, and biochemical parameters. RESULTS: In total, 298 patients were included in our analysis. Taste changes were reported in 38% of this cohort. Taste changes were significantly associated with upper gastrointestinal symptoms (nausea, vomiting, anorexia, and dry/sore mouth) and malnutrition. CONCLUSIONS: Our findings indicate that taste changes are highly prevalent and probably under-recognized in ESKD. Further investigation of the association with malnutrition is needed. Future trials are needed to evaluate strategies to manage taste changes in this population.

Moral Distress in Nephrology: Perceived Barriers to Ethical Clinical Care.

Moral distress occurs when individuals are unable to act in accordance with what they believe to be ethically correct or just. It results from a discrepancy between a clinician's perception of "the right thing to do" and what is actually happening and is perpetuated by perceived constraints that limit the individual from speaking up or enacting change. Moral distress is reported by many clinicians in caring for patients with serious illness, including chronic kidney disease and kidney failure. If left unidentified, unexpressed, or unaddressed, moral distress may cause burnout, exhaustion, detachment, and ineffectiveness. At an extreme, moral distress may lead to a desire to abandon the speciality entirely. This article offers an international perspective on moral distress in nephrology in diverse contexts and health care systems. We examine and discuss the sociocultural factors that contribute to moral distress in nephrology and offer suggestions for interventions from individual provider, facility, and health care systems perspectives to reduce the impact of moral distress on nephrology providers.

The Pathophysiology and Management of Taste Changes in Chronic Kidney Disease: A Review.

One of the most disabling, yet neglected, symptom of patients with chronic kidney disease (CKD) is alteration in taste. The purpose of this review is to examine the extent and content of research around this symptom in CKD with the goals of (1) identifying gaps in current research knowledge and (2) guiding future research. The review summarizes the basic anatomy and physiology of taste followed by analysis of the epidemiology, pathophysiology, and management strategies for taste changes in patients with CKD.

Access to Pain Management as a Human Right.

The concept of access to pain management as a human right has gained increasing currency in recent years. Commencing as individual advocacy, it was later embraced by the disciplines of pain medicine and palliative care and by mainstream human rights organizations.Today, United Nations and regional human rights bodies have accepted the concept and incorporated it into key human rights reports, reviews, and standards. We review the foundations in law of this right and the obligations that flow from it to governments. We analyze the nature and content of the obligation in the context of acute, chronic nonmalignant and cancer pain.Finally, we examine this right in light of the twin crises of inadequate access to pain management and the opioid crisis in the United States and other nations.

Retrospective chart review to assess domains of quality of death (recognition of dying, appropriate limitations, symptom monitoring, anticipatory prescribing) of patients dying in the acute hospital under the care of a nephrology service with renal supportive care support over time.

AIM: To explore the quality of deaths in an acute hospital under a nephrology service at two teaching hospitals in Sydney with renal supportive care services over time. METHODS: Retrospective chart review of all deaths in the years 2004, 2009 and 2014 at St George Hospital (SGH) and in 2014 at the Concord Repatriation General Hospital. Domains assessed were recognition of dying, invasive interventions, symptom assessment, anticipatory prescribing, documentation of spiritual needs and bereavement information for families. End-of-life care plan (EOLCP) use was also evaluated at SGH. RESULTS: Over 90% of patients were recognized to be dying in all 3 years at SGH. Rates of interventions in the last week of life were low and did not differ across the 3 years. There was a significant increase in the prescription of anti-psychotic, anti-emetic and anti-cholinergic medication over the years at SGH. Use of EOLCP was significantly higher at SGH, and their use improved several quality domains. Of all deaths, 68% were referred to palliative care at SGH and 33% at Concord Repatriation General Hospital (not significant). Cessation of observations and non-essential medications and documentation of bereavement information given to families was low across both sites in all years, although this significantly improved when EOLCP were used. CONCLUSION: While acute teams are good at recognizing dying, they need support to care for dying patients. The use of EOLCP in acute services can facilitate improvements in caring for the dying. Renal supportive care services need time to become embedded in the culture of the acute hospital.

Integration of Consortia Recommendations for Justification of Animal Use Within Current and Future Drug Development Paradigms.

The pharmaceutical and biotechnology industries continually review the requirements for, and relevance of, safety assessment strategies. Various industry consortia are currently discussing and reviewing data on a range of topics with respect to regulatory toxicology programs. These consortia are charged with critical evaluation of data and the identification of opportunities to promote best practice and to introduce improved approaches to safety assessment. Such improvements may include enhanced predictivity, more efficient ways of working, and opportunities for promoting and implementing the 3Rs (replacement, refinement, or reduction). As each consortium is considering a distinct question, individual outputs and recommendations could be perceived to be conflicting. However, a common theme embraced by the consortia represented here is exploration of the most appropriate use of animals for the safety assessment of new medicinal products. This short review summarizes presentations and discussions from a symposium describing the work of four industry consortia and considers whether their recommendations can be aligned into realistic approaches to improve future toxicology testing strategies, highlighting justification for the appropriate use of different animal species and opportunities for reductions in animal use without compromising patient safety.

iConnect CKD - virtual medical consulting: A web-based chronic kidney disease, hypertension and diabetes integrated care program.

AIMS: Chronic kidney disease patients overwhelm specialist services and can potentially be managed in the primary care (PC). Opportunistic screening of high risk (HR) patients and follow-up in PC is the most sustainable model of care. A 'virtual consultation' (VC) model instead of traditional face to face (F2F) consultations was used, aiming to assess efficacy and safety of the model. METHODS: Seventy patients were recruited from PC sites and hospital clinics and followed for 1 year. The HR patients (eGFR < 30 mL/min/1.73m2 +/- albuminuria >30 mg/mmol/L) were randomized to either VC or F2F. Patients were monitored in 6 monthly follow-up cycles by a Clinical Nurse Specialist. The specialist team provided virtual or clinical support and included a Nephrologist, Endocrinologist, Cardiologist and Renal 'Palliative' Supportive Care. RESULTS: Sixty one (87%) patients were virtually tracked or consulted with 14 (23%) being HR. At 12 months, there was no difference in outcomes between VC and F2F patients. All patients were successfully monitored. General practitioners reported a high level of satisfaction and supported the model, but found software integration challenging. Patients found the system attractive and felt well managed. Specialist consults occurred within a week, and if a second specialist opinion was required, it took another 2 weeks. CONCLUSIONS: The programme demonstrated safe, expedited and efficient follow up with a clinical and web based programme. Support from the general practitioners and patients was encouraging, despite logistical issues. Ongoing evaluation of VC services will continue and feasibility to larger networks and more chronic diseases remains the long term goal.

Current strategies in the non-clinical safety assessment of biologics: New targets, new molecules, new challenges.

Nonclinical safety testing of biopharmaceuticals can present significant challenges to human risk assessment with these innovative and often complex drugs. Emerging topics in this field were discussed recently at the 2016 Annual US BioSafe General Membership meeting. The presentations and subsequent discussions from the main sessions are summarized. The topics covered included: (i) specialty biologics (oncolytic virus, gene therapy, and gene editing-based technologies), (ii) the value of non-human primates (NHPs) for safety assessment, (iii) challenges in the safety assessment of immuno-oncology drugs (T cell-dependent bispecifics, checkpoint inhibitors, and costimulatory agonists), (iv) emerging therapeutic approaches and modalities focused on microbiome, oligonucleotide, messenger ribonucleic acid (mRNA) therapeutics, (v) first in human (FIH) dose selection and the minimum anticipated biological effect level (MABEL), (vi) an update on current regulatory guidelines, International Council for Harmonization (ICH) S1, S3a, S5, S9 and S11 and (vii) breakout sessions that focused on bioanalytical and PK/PD challenges with bispecific antibodies, cytokine release in nonclinical studies, determining adversity and NOAEL for biologics, the value of second species for toxicology assessment and what to do if there is no relevant toxicology species.

The Legal Doctrine of Informed Consent and Renal Dialysis - Do Patients Really Consent?

A doctor has a legal duty to secure the informed consent of a patient prior to performing a medical or surgical procedure. The elements of the legal doctrine of informed consent include capacity, voluntariness and the provision and understanding of relevant information. This article examines the doctrine in the context of renal dialysis. Dialysis is a complex therapy that impacts upon quality of life and has limited survival advantage in some patients. It is likely that informed consent is often not fully integrated into the care of patients commencing dialysis. The article analyses the common law doctrine of informed consent as it relates to dialysis and presents the findings of a retrospective study of the adequacy of the consent process based on interviews with dialysis patients who commenced dialysis in the previous 12 months. It concludes with recommendations for improvement in practice.

Sleep Disorders, Restless Legs Syndrome, and Uremic Pruritus: Diagnosis and Treatment of Common Symptoms in Dialysis Patients.

Maintenance dialysis patients experience a high burden of physical and emotional symptoms that directly affect their quality of life and health care utilization. In this review, we specifically highlight common troublesome symptoms affecting dialysis patients: insomnia, restless legs syndrome, and uremic pruritus. Epidemiology, pathophysiology, and evidence-based current treatment are reviewed with the goal of providing a guide for diagnosis and treatment. Finally, we identify multiple additional areas of further study needed to improve symptom management in dialysis patients.

'To die with dignity': an update on Palliative Care.

Significant developments have occurred in the discipline of palliative care in the modern era. This paper shall explore those developments, challenge some widely held misconceptions about the role and daily practice of the discipline, highlight the growing recognition of the role of palliative care in non-malignant diseases, briefly discuss innovations in symptom management and reflect on the underlying principles, maturation and challenges faced by the discipline.

Nutrition in Renal Supportive Care: Patient-driven and flexible.

Renal Supportive Care is an alternative treatment pathway in advanced chronic kidney disease that is being increasingly adopted, particularly in the elderly. Renal Supportive Care uses principles of palliative care and has been developed to enhance the care for dialysis patients with a high symptom burden and those being managed on a non-dialysis pathway. Nutrition management is often an under-recognized component of care and can play an important role in improving patients' quality of life to reduce symptom burden, support physical function and independence and provide appropriate counselling to patients and their families to ensure the goals of Renal Supportive Care are met. Nutrition interventions need to target patient and treatment goals, with frequent monitoring to ensure patient needs are being met. This review outlines available literature on this topic and suggests some practical ways in which nutrition can be enhanced for these patients.