Cardiovascular disease: priorities and outcomes in end stage kidney disease

Introduction End stage kidney disease (ESKD) accounts for 5-10 million deaths annually worldwide. The current treatment modalities for ESKD include dialysis, transplant and supportive care. The leading cause of death for people with ESKD is cardiovascular disease (CVD). CVD is a collective term for disease affecting the heart and blood vessels including coronary, cerebral and peripheral blood vessels. CVD causes significant morbidity and has a substantial impact on quality of life for people with ESKD. Improving cardiovascular outcomes for people living with ESKD is a priority. The escalating incidence of chronic kidney disease, its progression to ESKD and the high burden of cardiovascular disease has generated an increasing amount of research in the ESKD population. The ESKD population have previously been under-represented in clinical trials and current trials in ESKD have infrequently and inconsistently reported CVD outcomes. It is important to standardise outcomes used in research. When outcome reporting is standardised it enables comparisons of findings across trials, populations and eras. It is important that the outcomes reflect patient priorities and are relevant to patients and clinicians for use in shared decision making. The Standardised Outcomes in Nephrology Group (SONG) is an international initiative to establish a set of core outcomes and outcome measures across the spectrum of kidney disease for trials and other forms of research. The SONG-Haemodialysis (SONG - HD) initiative is developing a core outcome set for use in haemodialysis. As part of SONG-HD, CVD (as well as fatigue, vascular access and mortality) has been identified as important to all stakeholders and included in the core outcome set for haemodialysis. This requires appropriate measures of CVD to be identified and used. The first aim of this thesis was to achieve consensus on a CVD outcome measure for use in haemodialysis trials. In approaching this goal I first needed to ascertain the current use of cardiovascular outcomes (Chapter 2) and then determine which ones were important to all stakeholders (Chapter 3). Consensus over which is the most appropriate measure of CVD for use in trials in people on haemodialysis (Chapter 4) will allow improved standardisation of cardiovascular outcome reporting, reducing research wastage and will propel forward cardiovascular research to improve morbidity and mortality in this high risk population. The second aim of this thesis was to further examine some of the prioritised outcomes and to review the patterns and risks of CVD in the ESKD population. The magnitude of risk for cardiac events and cardiac deaths in people with ESKD relative to the general population and the changes over time are not well described. I hypothesised that the magnitude of risk remained high in the ESKD population and that epidemiological improvements seen in CVD outcomes in the general population have not been mirrored in the ESKD population (Chapters 5 and 6). CVD and more specifically cerebrovascular disease can lead to significant cognitive impairment which has a substantial impact on the ability of ESKD patients to understand their disease, interpret education and be involved in shared decision making. The patterns of cognitive deficit in the ESKD population are not well understood and I hypothesised that cognitive deficits in the ESKD population may be different to those found in the general population and may differ by modality of renal replacement therapy. Standardising CVD outcomes, examining the epidemiology of CVD in ESKD and comparing the trends and patterns to the general population can drive hypotheses into potential causative mechanisms and new treatments. I present this thesis as a hybrid of published work, work currently under peer review for publication and work submitted for publication on the theme of priorities and outcomes in ESKD

Estimation of cardiac output and systemic vascular resistance using a multivariate regression model with features selected from the finger photoplethysmogram and routine cardiovascular measurements

BACKGROUND: Cardiac output (CO) and systemic vascular resistance (SVR) are two important parameters of the cardiovascular system. The ability to measure these parameters continuously and noninvasively may assist in diagnosing and monitoring patients with suspected cardiovascular diseases, or other critical illnesses. In this study, a method is proposed to estimate both the CO and SVR of a heterogeneous cohort of intensive care unit patients (N=48). METHODS: Spectral and morphological features were extracted from the finger photoplethysmogram, and added to heart rate and mean arterial pressure as input features to a multivariate regression model to estimate CO and SVR. A stepwise feature search algorithm was employed to select statistically significant features. Leave-one-out cross validation was used to assess the generalized model performance. The degree of agreement between the estimation method and the gold standard was assessed using Bland-Altman analysis. RESULTS: The Bland-Altman bias ±precision (1.96 times standard deviation) for CO was -0.01 ±2.70 L min(-1) when only photoplethysmogram (PPG) features were used, and for SVR was -0.87 ±412 dyn.s.cm(-5) when only one PPG variability feature was used. CONCLUSIONS: These promising results indicate the feasibility of using the method described as a non-invasive preliminary diagnostic tool in supervised or unsupervised clinical settings

Nephrologists' perspectives on defining and applying patient-centered outcomes in hemodialysis

Background and objectives: Patient centeredness is widely advocated as a cornerstone of health care, but it is yet to be fully realized, including in nephrology. Our study aims to describe nephrologists' perspectives on defining and implementing patient-centered outcomes in hemodialysis. Design, setting, participants, & measurements: Face-to-face, semistructured interviews were conducted with 58 nephrologists from 27 dialysis units across nine countries, including the United States, the United Kingdom, Australia, Austria, Belgium, Canada, Germany, Singapore, and New Zealand. Transcripts were thematically analyzed. Results: We identified five themes on defining and implementing patient-centered outcomes in hemodialysis: explicitly prioritized by patients (articulated preferences and goals, ascertaining treatment burden, defining hemodialysis success, distinguishing a physician-patient dichotomy, and supporting shared decision making), optimizing wellbeing (respecting patient choice, focusing on symptomology, perceptible and tangible, and judging relevance and consequence), comprehending extensive heterogeneity of clinical and quality of life outcomes (distilling diverse priorities, highly individualized, attempting to specify outcomes, and broadening context), clinically hamstrung (professional deficiency, uncertainty and complexity in measurement, beyond medical purview, specificity of care, mechanistic mindset [focused on biochemical targets and comorbidities], avoiding alarm, and paradoxical dilemma), and undermined by system pressures (adhering to overarching policies, misalignment with mandates, and resource constraints). Conclusions: Improving patient-centered outcomes is regarded by nephrologists to encompass strategies that address patient goals and improve wellbeing and treatment burden in patients on hemodialysis. However, efforts are hampered by ambiguities about how to prioritize, measure, and manage the plethora of critical comorbidities and broader quality of life outcomes in a care setting that is technically demanding and driven by biochemical targets. Identifying critical patient-important outcomes and mechanisms for integrating them into practice may help to deliver patient-centered care in hemodialysis and other chronic disease settings

Range and Consistency of Cardiovascular Outcomes Reported by Clinical Trials in Kidney Transplant Recipients: A Systematic Review

International audienceCardiovascular disease is a major cause of morbidity and mortality in kidney transplant recipients. Trial evidence to improve cardiovascular outcomes is limited by inconsistent reporting of outcomes, which may also lack patient-relevance. This study aimed to assess the range and consistency of cardiovascular outcomes reported by contemporary trials in kidney transplant recipients.Methods: A systematic review of all randomized controlled trials involving adult kidney transplant recipients that reported at least 1 cardiovascular outcome from January 2012 to December 2019 was performed, including Embase, MEDLINE, Cochrane, and ClinicalTrials.gov electronic databases. Trial characteristics were extracted and all levels of specification of the cardiovascular outcome measures reported were analyzed (the measure definition, metric' and method of aggregation). Measures assessing a similar aspect of cardiovascular disease were categorized into outcomes.Results: From 93 eligible trials involving 27 609 participants, 490 outcome measures were identified. The outcome measures were grouped into 38 outcomes. A cardiovascular composite was the most common outcome reported (40 trials, 43%) followed by cardiovascular mortality (42%) and acute coronary syndrome (31%). Cardiovascular composite was also the most heterogeneous outcome with 77 measures reported followed by cardiovascular mortality (n = 58) and inflammatory biomarkers (n = 51). The most common cardiovascular composite outcome components reported were major cardiovascular events (18 trials), stroke unspecified (11 trials), and myocardial infarction unspecified (10 trials).Conclusions: There is substantial heterogeneity in cardiovascular outcome reporting in kidney transplant trials