Achieving shared decision-making in patients with Advanced Chronic Kidney Disease and End-Stage Renal Disease can be time consuming and labor-intensive. An important concept in how to provide Renal supportive care to these patients would be frailty. We will now introduce the term frailty in this lecture, which will be used repeatedly afterwards. What does frailty mean in the medical literature? In lame language, frailty is described as the condition of being weak and delicate, and the weakness in human character or morals, as illustrated in the Oxford dictionary. However, in the medical literature, frailty is defined as a geriatric syndrome which covers a wide spectrum of degenerated phenotypes that do not fall into specific disease categories. Indeed, frailty is different from the traditional definition of a syndrome in that frailty does not specifically pinpoint an organ or a physiological system as the origin of this degenerated phenotype. Frailty describes a combination of symptoms and signs that in aggregate, contribute to the age-related vulnerability to adverse environment or internal derangement. Frailty also represents a state of decreased reserve and resistance to stressors and a continuous process of cumulative health-related deficits across different organ systems. Since the inception of the frailty concept, it has been found to be highly prevalent among geriatric population. Up to 7 percent to 12 percent of community-dwelling adults higher than 65 years old. The accurate identification of frailty used to be difficult due to its vague conceptualization until 2001, when Professor [inaudible] operationalized frailty using five concrete components including unintentional weight loss, weakness, exhaustion, slow gate, and low physical activity. Professor [inaudible] subsequently tested and validated another approach for quantifying frailty. Based on the cumulation of different deficits over a diverse spectrum of health dimensions. The assessment of frailty has now evolved to include numerous assessment methods including physical measurement, self-report questionnaire-based assessment, database-driven identification, and one or more combinations of the above approaches. Regardless of definitions and the approach being used, those with frailty, especially lows, when frailty becomes more severe, have a higher risk of developing adverse outcomes including higher mortality, risk of hospitalization, health care utilization compared to those without frailty. The pathophysiology of frailty, can be complex. A large body of literature suggests that multisystem pathologies account for the development of royalty in any given individual including chronic inflammation, immune activation, musculoskeletal degeneration, endocrinological, aberrations, etc. Among the pathological processes listed above, chronic inflammation is likely instrumental. As inflammation has been intricately connected with biological aging. This has been supported by pre-imposed studies, showing that older adults have relatively higher circulatory inflammatory cytokines, such as interleukin 6 and c-reactive protein compared to younger ones. Immune cells are also selectively activated in those with frailty. Frail individuals have an increased proportion of CDA positive plus CD28 negative T-cells and CCR5 positive T-cells. Frail individuals also have an up-regulation of CXCL10 in there monocytes. To support the theory, anecdotal studies further show that anti-inflammatory medications, such as statins can reduce the risk of incident royalty. Apart from inflammation, musculoskeletal effects are also cardinal features and contributors to frailty. Among these defects, sarcopenia, the lost or dysfunctional muscle tissues, and osteoporosis, the loss of bone mass are core players. In adequate nutrition the absence of exercise habits, age related loss of muscle mass and strength, the decrease production of growth hormones, estrogen and testosterone, and vitamin D deficiency or insufficiency may all be responsible for sarcopenia development. Similar settings also apply to the development of osteoporosis. Finally, metabolic perturbations, such as metabolic syndrome and insulin resistance, are also found to be risk factors for frailty in older adults. But the detailed mechanism remains to be elucidated. Studies gradually uncover that royalty exist not only among individuals of advanced age, but also among those with different types of chronic illnesses such as diabetes mellitus, congestive heart failure, coronary atherosclerosis, chronic obstructive pulmonary disease, Parkinsonism, and even Alzheimer disease. Chronic diseases are considered important determinants of a predisposing factors for frailty. Frailty may alter the risk benefit ratio of a given treatment against chronic diseases. Frailty may even act as an effect modifier. Modifying the pros and cons of different treatments signifying its utility. Not only as the diagnostic maker and treatment target but also as a feature that facilitate the treatment decision-making. The research group in National Taiwan University Hospital, the cohort of geriatric nephrology in NTUH or the coach and study group has devoted much effort to the study of frailty in patients with chronic kidney disease and end-stage renal disease. We have tried to test and affirm the utility of multiple different questionnaires to assess frailty in these patients with renal dysfunction including Strawbridge questionnaire, Edmonton Frail Scale, the Frail scale, Groningen Frail Indicator, G8 questionnaire and Tilburg Frail Indicator. Through our summary of the dimensions of Frailty inherent to each scale which is shown in this slide, you can see that different tools plays emphasis anger diverse spectrum of health deficit including in the construct of frailty. For example, Strawbridge questionnaire examines the physical, nutrition, cognitive, and sensory defects of the enrollees while Edmonton Frail Scale asses a more comprehensive list of frailty components including cognition, functional status, social support, medication use, nutrition, mood status, [inaudible] integrity and activities of daily living supplemented by a self report evaluation of the general health status. G8 questionnaire focus predominantly on patients with cancer and aims to examine multiple categories intimately related to oncology care such as appetite, weight loss, mobility and psychological performance. Among these six questionnaires we tested, the frail scale or simple frail scale is the relatively short but easy-to-use questionnaire that specifically captures the construct of frailty using five components. That is fatigue, resistance, ambulation, illness, and loss of weight thus the acronym frail. In the further study, we identify that prevalence of frailty in [inaudible] with end-stage renal disease range from 20 percent to as high as 80 percent. Patients with end-stage renal disease have different degrees of impairment in the diverse spectrum of frailty subcategories among which physical impairment, functional deterioration and poor self-rated health are the most common ones. More importantly we discovered that frail scale outperform the other questionnaires in terms of result correlation with dialysis related complications. This is an important starting point in characterizing the epidemiology of frailty and it's pathophysiologic relevance in patients with renal dysfunction in Taiwan.
