Pathogenesis and Prevention of Vascular Access Failure

Dialysis vascular access failure is common, is rated as a critical priority by both patients and health professionals, and is associated with excess morbidity, mortality and healthcare costs. This chapter will discuss the mechanisms underpinning vascular access failure as well as strategies for preventing this adverse outcome, including systemic medical therapies (such as antiplatelet agents, fish oils, statins, inhibitors of the renin-angiotensin-aldosterone system, and calcium channel blockers), and local therapeutic interventions including innovative surgical techniques, minimally invasive AVF creation, far infra-red therapy, perivascular application of recombinant elastase, endothelial loaded gel foam wrap (Vascugel), and antiproliferative agents such as sirolimus (Coll-R) and paclitaxel-coated balloon angioplasty

Cardiovascular outcomes reported in hemodialysis trials

Patients on long-term hemodialysis are at very high risk for cardiovascular disease but are usually excluded from clinical trials conducted in the general population or in at-risk populations. There are no universally agreed cardiovascular outcomes for trials conducted specifically in the hemodialysis population. In this review, we highlight that trials reporting cardiovascular outcomes in hemodialysis patients are usually of short duration (median 3 to 6 months) and are small (59% of trials have \u3c100 participants). Overall, the cardiovascular outcomes are very heterogeneous and may not reflect outcomes that are meaningful to patients and clinicians in supporting decision making, as they are often surrogates of uncertain clinical importance. Composite outcomes used in different trials rarely share the same components. In a field in which a single trial is often insufficiently powered to fully assess the clinical and economic impact of interventions, differences in outcome reporting across trials make the task of meta-analysis and interpretation of all the available evidence challenging. Core outcome sets are now being established across many specialties in health care to prevent these problems. Through the global Standardized Outcomes in Nephrology-Hemodialysis initiative, cardiovascular disease was identified as a critically important core domain to be reported in all trials in hemodialysis. Informed by the current state of reporting of cardiovascular outcomes, a core outcome measure for cardiovascular disease is currently being established with involvement of patients, caregivers, and health professionals. Consistent reporting of cardiovascular outcomes that are critically important to hemodialysis patients and clinicians will strengthen the evidence base to inform care in this very high-risk population

The Symptom Monitoring with Feedback Trial (SWIFT):protocol for a registry‑based cluster randomised controlled trial in haemodialysis

BACKGROUND: Kidney failure prevalence is increasing worldwide. Haemodialysis, peritoneal dialysis or kidney transplantation are undertaken to extend life with kidney failure. People receiving haemodialysis commonly experience fatigue, pain, nausea, cramping, itching, sleeping difficulties, anxiety and depression. This symptom burden contributes to poor health-related quality of life (QOL) and is a major reason for treatment withdrawal and death. The Symptom monitoring WIth Feedback Trial (SWIFT) will test the hypothesis that regular symptom monitoring with feedback to people receiving haemodialysis and their treating clinical team can improve QOL. METHODS: We are conducting an Australia and New Zealand Dialysis and Transplant (ANZDATA) registry-based cluster randomised controlled trial to determine the clinical- and cost-effectiveness at 12 months, of 3-monthly symptom monitoring using the Integrated Palliative Outcome Scale-Renal (IPOS-Renal) survey with clinician feedback, compared with usual care among adults treated with haemodialysis. Participants complete symptom scoring using a tablet, which are provided to participants and to clinicians. The trial aims to recruit 143 satellite haemodialysis centres, (up to 2400 participants). The primary outcome is change in health-related QOL, as measured by EuroQol 5-Dimension, 5-Level (EQ-5D-5L) instrument. Secondary outcomes include overall survival, symptom severity (including haemodialysis-associated fatigue), healthcare utilisation and cost-effectiveness. DISCUSSION: SWIFT is the first registry-based trial in the Australian haemodialysis population to investigate whether regular symptom monitoring with feedback to participants and clinicians improves QOL. SWIFT is embedded in the ANZDATA Registry facilitating pragmatic recruitment from public and private dialysis clinics, throughout Australia. SWIFT will inform future collection, storage and reporting of patient-reported outcome measures (PROMs) within a clinical quality registry. As the first trial to rigorously estimate the efficacy and cost-effectiveness of routine PROMs collection and reporting in haemodialysis units, SWIFT will provide invaluable information to health services, clinicians and researchers working to improve the lives of those with kidney failure. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620001061921. Registered on 16 October 2020 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06355-0

Establishing a core outcome set for peritoneal dialysis : report of the SONG-PD (standardized outcomes in nephrology-peritoneal dialysis) consensus workshop

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD

Implementing core outcomes in kidney disease: report of the Standardized Outcomes in Nephrology (SONG) implementation workshop.

There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials. We convened a SONG Implementation Workshop to discuss the implementation of core outcomes. Eighty-two patients/caregivers and health professionals participated in plenary and breakout discussions. In this report, we summarize the findings of the workshop in two main themes: socializing the concept of core outcomes, and demonstrating feasibility and usability. We outline implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes

Core Outcomes Set for Trials in People With Coronavirus Disease 2019.

OBJECTIVES: The outcomes reported in trials in coronavirus disease 2019 are extremely heterogeneous and of uncertain patient relevance, limiting their applicability for clinical decision-making. The aim of this workshop was to establish a core outcomes set for trials in people with suspected or confirmed coronavirus disease 2019. DESIGN: Four international online multistakeholder consensus workshops were convened to discuss proposed core outcomes for trials in people with suspected or confirmed coronavirus disease 2019, informed by a survey involving 9,289 respondents from 111 countries. The transcripts were analyzed thematically. The workshop recommendations were used to finalize the core outcomes set. SETTING: International. SUBJECTS: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers). INTERVENTIONS: None. MEASUREMENTS: None. MAIN RESULTS: Six themes were identified. "Responding to the critical and acute health crisis" reflected the immediate focus on saving lives and preventing life-threatening complications that underpinned the high prioritization of mortality, respiratory failure, and multiple organ failure. "Capturing different settings of care" highlighted the need to minimize the burden on hospitals and to acknowledge outcomes in community settings. "Encompassing the full trajectory and severity of disease" was addressing longer term impacts and the full spectrum of illness (e.g. shortness of breath and recovery). "Distinguishing overlap, correlation and collinearity" meant recognizing that symptoms such as shortness of breath had distinct value and minimizing overlap (e.g. lung function and pneumonia were on the continuum toward respiratory failure). "Recognizing adverse events" refers to the potential harms of new and evolving interventions. "Being cognizant of family and psychosocial wellbeing" reflected the pervasive impacts of coronavirus disease 2019. CONCLUSIONS: Mortality, respiratory failure, multiple organ failure, shortness of breath, and recovery are critically important outcomes to be consistently reported in coronavirus disease 2019 trials

International Survey to Establish Prioritized Outcomes for Trials in People With Coronavirus Disease 2019.

OBJECTIVES: There are over 4,000 trials conducted in people with coronavirus disease 2019. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for coronavirus disease 2019 trials. DESIGN: In an online survey conducted in English, Chinese, Italian, Portuguese, and Spanish languages, adults with coronavirus disease 2019, their family members, health professionals, and the general public rated the importance of outcomes using a 9-point Likert scale (7-9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analyzed thematically. SETTING: International. SUBJECTS: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public, and health professionals (including clinicians, policy makers, regulators, funders, and researchers). INTERVENTIONS: None. MEASUREMENTS: None. MAIN RESULTS: In total, 9,289 participants from 111 countries (776 people with coronavirus disease 2019 or family members, 4,882 health professionals, and 3,631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia, and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean > 7.5, median ≥ 8, and > 70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems, and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating, and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes. CONCLUSIONS: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals.The project is funded by the Flinders University and the National COVID-19 Clinical Evidence Taskforce, convened by the Australian Living Evidence Consortium, hosted by Cochrane Australia, School of Public Health and Preventive Medicine, Monash University supported by the Australian Government, Victorian Department of Health and Human Services, Ian Potter Foundation, Walter Cottman Endowment Fund (managed by Equity Trustees) and the Lord Mayor's Charitable Foundation). AT is supported by The University of Sydney Robinson Fellowship. ACM is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z

Core outcome domains for trials in autosomal dominant polycystic kidney disease: An international Delphi survey

Rationale & Objective Outcomes reported in trials involving patients with autosomal dominant polycystic kidney disease (ADPKD) are heterogeneous and rarely include patient-reported outcomes. We aimed to identify critically important consensus-based core outcome domains to be reported in trials in ADPKD. Study Design An international 2-round online Delphi survey was conducted in English, French, and Korean languages. Setting & Participants Patients/caregivers and health professionals completed a 9-point Likert scale (7-9 indicating critical importance) and a Best-Worst Scale. Analytical Approach The absolute and relative importance of outcomes were assessed. Comments were analyzed thematically. Results 1,014 participants (603 [60%] patients/caregivers, 411 [40%] health professionals) from 56 countries completed round 1, and 713 (70%) completed round 2. The prioritized outcomes were kidney function (importance score, 8.6), end-stage kidney disease (8.6), death (7.9), blood pressure (7.9), kidney cyst size/growth (7.8), and cerebral aneurysm (7.7). Kidney cyst–related pain was the highest rated patient-reported outcome by both stakeholder groups. Seven themes explained the prioritization of outcomes: protecting life and health, directly encountering life-threatening and debilitating consequences, specificity to ADPKD, optimizing and extending quality of life, hidden suffering, destroying self-confidence, and lost opportunities. Limitations Study design precluded involvement from those without access to internet or limited computer literacy. Conclusions Kidney function, end-stage kidney disease, and death were the most important outcomes to patients, caregivers, and health professionals. Kidney cyst–related pain was the highest rated patient-reported outcome. Consistent reporting of these top prioritized outcomes may strengthen the value of trials in ADPKD for decision making

Hemodialysis vascular access in the elderly—getting it right

Choosing the optimal hemodialysis vascular access for the elderly patient is best achieved by a patient-centered coordinated multidisciplinary team approach that aligns the patient's end-stage kidney disease Life-Plan, i.e., the individual treatment approach (supportive care, time-limited or long-term kidney replacement therapy, or combination thereof) and selection of dialysis modality (peritoneal dialysis versus hemodialysis) with the most suitable dialysis access. Finding the right balance between the patient's preferences, the likelihood of access function and survival, and potential complications in the context of available resources and limited patient survival can be extremely challenging. The framework for choosing the most appropriate vascular access for the elderly presented in this review considers the individual end-stage kidney disease Life-Plan, the patient life expectancy, the likelihood of access function and survival, the timing of dialysis relative to access placement, prior access history, and patient preference. This complex decision-making process should be dynamic in order to accommodate patients’ changing needs and life and health circumstances. Effective and timely communication between the patient, their caregivers, and treating team is key to delivering truly patient-centered care. Delivering this care also requires overcoming the limitations of the currently available evidence that is predominantly based on observational data with its inherent risks of bias. While challenging, future randomized controlled studies exploring the risks, benefits, costs, and timing of placement of available access types in the elderly are required to help us “get it right” for our patients