Identifying Malnutrition in End-stage Renal Disease (ESRD) (P12-037-19).

Objectives: Malnutrition and appetite disturbances, such as anorexia, are commonly reported amongst hemodialysis patients. Nutrition management is a complex issue in ESRD and greater understanding is needed into the associated clinical mediators in ESRD. However, there is currently limited data on anorexia and the pathophysiology framework involved.The aim of this study was to assess the relationship between appetite score and associated clinical biomarkers as a means to identify malnutrition. This work is part of an ongoing international multicenter effort to better define and develop treatment strategies for cachexia in patients with ESRD. Methods: A cross-sectional analysis study included 106 patients from two hemodialysis (HD) units within the United Kingdom (U.K). Appetite score was assessed using the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). Clinical bio-makers included Body Mass Index (BMI), Albumin and C-reactive protein (CRP). Correlations between FAACT and clinical bio-markers were determined using Spearman's rho for non-normally distributed scales. Results: There was no significant relationship between FAACT and albumin levels (r = 0.14; P = 0.16) or BMI (r = 0.28; P = .19). However, there was a moderate and significant negative correlation between FAACT and CRP levels (r = 0.31; P < 0.001) indicating an inverse relationship between appetite (e.g., decreased FAACT score) and CRP levels (e.g., higher inflammation). Conclusions: We found a significant and incremental relationship between inflammation and anorexia which is supported by previous research. The FAACT may be a useful tool in identifying patients at higher risk of malnutrition-inflammation cachexia syndrome which has been associated with higher hospitalization and morality rates. Nutritional status and inflammation are important aspects of clinical practice in ESRD. A more focused approach to anorexia in ESRD is warranted. Funding Sources: This study was funded by the Public Health Agency (Ref: STL/5179/15) and the Northern Ireland Kidney Research Fund. Noble et al., was funded by the National Institute for Health Research and the Health and Social Care Research and Development Division of the Public Health Agency Office Northern Ireland NIHR (CDV/4872/13)

Estimating the Prevalence of Muscle Wasting, Weakness, and Sarcopenia in Hemodialysis Patients.

OBJECTIVES: Haemodialysis (HD) patients suffer from nutritional problems, which include muscle wasting, weakness, and cachexia, and are associated with poor clinical outcomes. The European Working Group for Sarcopenia in Older People (EWGSOP) and Foundations for the National Institute of Health (FNIH) have developed criteria for the assessment of sarcopenia, including the use of non-invasive techniques such as bioelectrical impedance assessment (BIA), anthropometry, and hand grip strength (HGS) dynamometry. This study investigated the prevalence of muscle wasting, weakness, and sarcopenia using the EWGSOP and FNIH criteria. METHODS: BIA was performed in 24 females (f) and 63 males (m) in the post-dialysis period. Total skeletal muscle mass and appendicular skeletal muscle mass were estimated and index values (i.e., muscle mass divided by height2 [kg/m2]) were calculated (Total Skeletal Muscle Index (TSMI) and Appendicular Skeletal Muscle Index (ASMI)). Mid-arm circumference and triceps skin-fold thickness were measured and mid-upper arm muscle circumference (MUAMC) calculated. HGS was measured using a standard protocol and Jamar dynamometer. Suggested cut-points for low muscle mass and grip strength were utilized using the EWGSOP and FNIH criteria with prevalence estimated, including sarcopenia. RESULTS: The prevalence varied depending on methodology: low TSMI (moderate and severe sarcopenia combined) was 55% for whole group: 21% (f) and 68% (m). Low ASMI was 32% for whole group: 25% (f) and 35% (m). Low MUAMC was 25% for whole group: 0% (f) and 30% (m). ASMI highly correlated with Body Mass Index (r = 0.78, P < .001) and MUAMC (r = 0.68, P < .001). Muscle weakness was high regardless of cut-points used (50-71% (f); 60-79% (m)). CONCLUSIONS: Internationally, this is the first study comparing measures of muscle mass (TSMM and ASMM by BIA and MUAMC) and muscle strength (HGS) using this specific methodology in a hemodialysis population. Future work is required to confirm findings

Establishing a clinical phenotype for cachexia in end stage kidney disease - study protocol.

BACKGROUND: Surveys using traditional measures of nutritional status indicate that muscle wasting is common among persons with end-stage kidney disease (ESKD). Up to 75% of adults undergoing maintenance dialysis show some evidence of muscle wasting. ESKD is associated with an increase in inflammatory cytokines and can result in cachexia, with the loss of muscle and fat stores. At present, only limited data are available on the classification of wasting experienced by persons with ESKD. Individuals with ESKD often exhibit symptoms of anorexia, loss of lean muscle mass and altered energy expenditure. These symptoms are consistent with the syndrome of cachexia observed in other chronic diseases, such as cancer, heart failure, and acquired immune deficiency syndrome. While definitions of cachexia have been developed for some diseases, such as cardiac failure and cancer, no specific cachexia definition has been established for chronic kidney disease. The importance of developing a definition of cachexia in a population with ESKD is underscored by the negative impact that symptoms of cachexia have on quality of life and the association of cachexia with a substantially increased risk of premature mortality. The aim of this study is to determine the clinical phenotype of cachexia specific to individuals with ESKD. METHODS: A longitudinal study which will recruit adult patients with ESKD receiving haemodialysis attending a Regional Nephrology Unit within the United Kingdom. Patients will be followed 2 monthly over 12 months and measurements of weight; lean muscle mass (bioelectrical impedance, mid upper arm muscle circumference and tricep skin fold thickness); muscle strength (hand held dynamometer), fatigue, anorexia and quality of life collected. We will determine if they experience (and to what degree) the known characteristics associated with cachexia. DISCUSSION: Cachexia is a debilitating condition associated with an extremely poor outcome. Definitions of cachexia in chronic illnesses are required to reflect specific nuances associated with each disease. These discrete cachexia definitions help with the precision of research and the subsequent clinical interventions to improve outcomes for patients suffering from cachexia. The absence of a definition for cachexia in an ESKD population makes it particularly difficult to study the incidence of cachexia or potential treatments, as there are no standardised inclusion criteria for patients with ESKD who have cachexia. Outcomes from this study will provide much needed data to inform development and testing of potential treatment modalities, aimed at enhancing current clinical practice, policy and education

Developing an Evidence and Theory Based Multimodal Integrative Intervention for the Management of Renal Cachexia: A Theory of Change

In this study, we aimed to develop a theoretical framework for a multimodal, integrative, exercise, anti-inflammatory and dietary counselling (MMIEAD) intervention for patients with renal cachexia with reference to how this addresses the underlying causal pathways for renal cachexia, the outcomes anticipated, and how these will be evaluated. We used a Theory of Change (ToC) approach to guide six steps. Step 1 included inputs from a workshop to obtain key stakeholder views on the potential development of a multimodal intervention for renal cachexia. Step 2 included the findings of a mixed-methods study with Health Care Practitioners (HCPs) caring for individuals with End Stage Kidney Disease (ESKD) and cachexia. Step 3 included the results from our systematic literature review on multimodal interventions for cachexia management. In step 4, we used the body of our research team's cachexia research and wider relevant research to gather evidence on the specific components of the multimodal intervention with reference to how this addresses the underlying causal pathways for renal cachexia. In steps 5 and 6 we developed and refined the ToC map in consultation with the core research team and key stakeholders which illustrates how the intervention components of MMIEAD interact to achieve the intended long-term outcomes and anticipated impact. The results of this study provide a theoretical framework for the forthcoming MMIEAD intervention for those with renal cachexia and in subsequent phases will be used to determine whether this intervention is effective. To the best of our knowledge no other multimodal intervention trials for cachexia management have reported a ToC. Therefore, this research may provide a useful framework and contribute to the ongoing development of interventions for cachexia management

Developing an Evidence and Theory Based Multimodal Integrative Intervention for the Management of Renal Cachexia: A Theory of Change

In this study, we aimed to develop a theoretical framework for a multimodal, integrative, exercise, anti-inflammatory and dietary counselling (MMIEAD) intervention for patients with renal cachexia with reference to how this addresses the underlying causal pathways for renal cachexia, the outcomes anticipated, and how these will be evaluated. We used a Theory of Change (ToC) approach to guide six steps. Step 1 included inputs from a workshop to obtain key stakeholder views on the potential development of a multimodal intervention for renal cachexia. Step 2 included the findings of a mixed-methods study with Health Care Practitioners (HCPs) caring for individuals with End Stage Kidney Disease (ESKD) and cachexia. Step 3 included the results from our systematic literature review on multimodal interventions for cachexia management. In step 4, we used the body of our research team's cachexia research and wider relevant research to gather evidence on the specific components of the multimodal intervention with reference to how this addresses the underlying causal pathways for renal cachexia. In steps 5 and 6 we developed and refined the ToC map in consultation with the core research team and key stakeholders which illustrates how the intervention components of MMIEAD interact to achieve the intended long-term outcomes and anticipated impact. The results of this study provide a theoretical framework for the forthcoming MMIEAD intervention for those with renal cachexia and in subsequent phases will be used to determine whether this intervention is effective. To the best of our knowledge no other multimodal intervention trials for cachexia management have reported a ToC. Therefore, this research may provide a useful framework and contribute to the ongoing development of interventions for cachexia management

Establishing a clinical phenotype for cachexia in end stage kidney disease - study protocol.

BackgroundSurveys using traditional measures of nutritional status indicate that muscle wasting is common among persons with end-stage kidney disease (ESKD). Up to 75% of adults undergoing maintenance dialysis show some evidence of muscle wasting. ESKD is associated with an increase in inflammatory cytokines and can result in cachexia, with the loss of muscle and fat stores. At present, only limited data are available on the classification of wasting experienced by persons with ESKD. Individuals with ESKD often exhibit symptoms of anorexia, loss of lean muscle mass and altered energy expenditure. These symptoms are consistent with the syndrome of cachexia observed in other chronic diseases, such as cancer, heart failure, and acquired immune deficiency syndrome. While definitions of cachexia have been developed for some diseases, such as cardiac failure and cancer, no specific cachexia definition has been established for chronic kidney disease. The importance of developing a definition of cachexia in a population with ESKD is underscored by the negative impact that symptoms of cachexia have on quality of life and the association of cachexia with a substantially increased risk of premature mortality. The aim of this study is to determine the clinical phenotype of cachexia specific to individuals with ESKD.MethodsA longitudinal study which will recruit adult patients&nbsp;with ESKD receiving haemodialysis attending a Regional Nephrology Unit within the United Kingdom. Patients will be followed 2 monthly over 12&nbsp;months and measurements of weight; lean muscle mass (bioelectrical impedance, mid upper arm muscle circumference and tricep skin fold thickness); muscle strength (hand held dynamometer), fatigue, anorexia and quality of life collected. We will determine if they experience (and to what degree) the known characteristics associated with cachexia.DiscussionCachexia is a debilitating condition associated with an extremely poor outcome. Definitions of cachexia in chronic illnesses are required to reflect specific nuances associated with each disease. These discrete cachexia definitions help with the precision of research and the subsequent clinical interventions to improve outcomes for patients suffering from cachexia. The absence of a definition for cachexia in an ESKD population makes it particularly difficult to study the incidence of cachexia or potential treatments, as there are no standardised inclusion criteria for patients with ESKD who have cachexia. Outcomes from this study will provide much needed data to inform development and testing of potential treatment modalities, aimed at enhancing current clinical practice, policy and education