Impaired kidney function and chronic kidney disease (CKD) leading to kidney failure and end-stage renal disease (ESRD) is a serious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD) risk. CKD is associated with multiple physiological and metabolic disturbances, including hypertension, dyslipidemia and the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal, inflammatory, and nutritional-metabolic factors may play key roles in CKD development and pathogenesis. These include raised proinflammatory cytokines, such as interleukin-1 and −6, tumor necrosis factor, altered hepatic acute phase proteins, including reduced albumin, increased C-reactive protein, and perturbations in normal anabolic hormone responses with reduced growth hormone-insulin-like growth factor-1 axis activity. Others include hyperactivation of the renin-angiotensin aldosterone system (RAAS), with angiotensin II and aldosterone implicated in hypertension and the promotion of insulin resistance, and subsequent pharmacological blockade shown to improve blood pressure, metabolic control and offer reno-protective effects. Abnormal adipocytokine levels including leptin and adiponectin may further promote the insulin resistant, and proinflammatory state in CKD. Ghrelin may be also implicated and controversial studies suggest activities may be reduced in human CKD, and may provide a rationale for administration of acyl-ghrelin. Poor vitamin D status has also been associated with patient outcome and CVD risk and may indicate a role for supplementation. Glucocorticoid activities traditionally known for their involvement in the pathogenesis of a number of disease states are increased and may be implicated in CKD-associated hypertension, insulin resistance, diabetes risk and cachexia, both directly and indirectly through effects on other systems including activation of the mineralcorticoid receptor. Insight into the multiple factors altered in CKD may provide useful information on disease pathogenesis, clinical assessment and treatment rationale such as potential pharmacological, nutritional and exercise therapies.

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 Analysis (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. BIA was performed in 24 females (f) and 63 males (m) in the post-dialysis period. Total skeletal muscle mass (TSMM) and appendicular skeletal muscle mass (ASMM) were estimated and index values (i.e., muscle mass divided by height 2 [kg/m 2 ]) 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 HGS were utilized from EWGSOP and FNIH criteria, with prevalence estimated, including sarcopenia. 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 (BMI) (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)). 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 haemodialysis population. Future work is required to confirm findings.

Malnutrition is common in heart failure (HF), and it is associated with higher hospital readmission and mortality rates. This review aims to answer the question whether nutritional interventions aiming to increase protein and energy intake are effective at improving outcomes for patients with HF who are malnourished or at risk of malnutrition or cachexia. Systematic searches of four databases (Medline, Embase, CINAHL and Cochrane Central Register of Controlled Trials (CENTRAL)) were conducted on 21 June 2019. Randomized controlled trials (RCTs) or other interventional studies using protein or energy supplementation for adult HF patients who are malnourished or at risk of malnutrition or cachexia were included. Two independent reviewers assessed study eligibility and risk of bias. Five studies (four RCTs and one pilot RCT) met the inclusion criteria. The majority of studies were small and of limited quality. The pooled weighted mean difference (WMD) for body weight showed a benefit from the nutritional intervention by 3.83 kg (95% confidence interval (CI) 0.17 to 7.50, P = 0.04) from three trials with no significant benefit for triceps skinfold thickness (WMD = − 2.14 mm, 95% CI − 9.07 to 4.79, P = 0.55) from two trials. The combination of personalized nutrition intervention with conventional treatment led to a decrease in all-cause mortality and hospital readmission in one study. Findings of this review suggest that nutritional interventions could potentially improve outcomes in HF patients who are malnourished or at risk of malnutrition. However, the strength of the evidence is poor, and more robust studies with a larger number of participants are needed.

ObjectiveBioelectrical impedance vector analysis (BIVA) and phase angle (PA) have been shown previously to indicate relative nutritional status in patients. The aim of this study was to investigate the application of BIVA and PA assessments in a cohort of frail older hospital patients and compare these assessments with malnutrition risk screening by MUST (Malnutrition Universal Screening Tool), and the MNA-SF® (Mini-Nutritional Assessment-Short Form). MethodsSixty-nine patients (n = 44 men; n = 25 women; age 82.1 ± 7.6 y [range 62-96 y]; body mass index 25.8 ± 5.4 kg/m2 [range 16.6-45.1 kg/m2]) were recruited from hospital wards specializing in the care of frail older individuals from the United Kingdom. Bioelectrical impedance assessment was performed at 50 khz frequency, BIVA was performed using raw impedance data, PA was calculated, and data were compared against reference population groups. Patients were categorized by malnutrition risk by MUST and MNA-SF.

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 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.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.

s u m m a r yBackground & aims: This cohort study aimed to investigate and compare the ability to predict malnutrition in a group of frail older hospital patients in the United Kingdom using the nutritional risk screening tools, MUST (malnutrition universal screening tool), MNA-SF Ò (mini nutritional assessment-short form) and bioelectrical impedance assessment (BIA) of body composition. Methods: MUST and MNA-SF was performed on 78 patients (49 males and 29 females, age: 82 y AE 7.9, body mass index (BMI): 25.5 kg/m 2 AE 5.4), categorised by nutritional risk, and statistical comparison and test reliability performed. BIA was performed in 66 patients and fat free mass (FFM), fat mass (FM) and body cell mass (BCM) and index values (kg/m 2 ) calculated and compared against reference values. Results: MUST scored 77% patients 'low risk', 9% 'medium risk' and 14% 'high risk', compared to MNA-SF categorisation: 9%, 46% and 45%, respectively (P < 0.000001). Reliability assessment found poor reliability between the screening tools (coefficient, r ¼ 0.4). Significant positive correlations were found between most variables (P < 0.05e<0.001); although females exhibited greater variation. FFM index analysis found 40% of males low/depleted, 21% borderline/at risk with 96% categorised by MNA-SF as either malnourished or at risk (MUST-35%). 29% males had low FM index and all appropriately classified by MNA-SF. 30% females had low FFM index or borderline, MNA-SF screening appropriately categorised 86% (compared to MUST-29%).Conclusions: This preliminary data may have significant clinical implications and highlights the potential ability of the MNA-SF and BIA to accurately assess malnutrition risk over MUST in frail older hospital patients.

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Background Research indicates that cachexia is common among persons with chronic illnesses and is associated with increased morbidity and mortality. However, there continues to be an absence of a uniformed disease-specific definition for cachexia in chronic kidney disease (CKD) patient populations. Objective The primary objective was to identify cachexia in patients receiving haemodialysis (HD) using a generic definition and then follow up on these patients for 12 months. Method This was a longitudinal study of adult chronic HD patients attending two hospital HD units in the UK. Multiple measures relevant to cachexia, including body mass index (BMI), muscle mass [mid-upper arm muscle circumference (MUAMC)], handgrip strength (HGS), fatigue [Functional Assessment of Chronic Illness Therapy (FACIT)], appetite [Functional Assessment of Anorexia/Cachexia Therapy (FAACT)] and biomarkers [C-reactive protein (CRP), serum albumin, haemoglobin and erythropoietin resistance index (ERI)] were recorded. Baseline analysis included group differences analysed using an independent t-test, dichotomized values using the χ2 test and prevalence were reported using the Statistical Package for the Social Sciences 24 (IBM, Armonk, NY, USA). Longitudinal analysis was conducted using repeated measures analysis. Results A total of 106 patients (30 females and 76 males) were recruited with a mean age of 67.2 years [standard deviation (SD) 13.18] and dialysis vintage of 4.92 years (SD 6.12). At baseline, 17 patients were identified as cachectic, having had reported weight loss (e.g. &gt;5% for &gt;6 months) or BMI &lt;20 kg/m2 and three or more clinical characteristics of cachexia. Seventy patients were available for analysis at 12 months (11 cachectic versus 59 not cachectic). The FAACT and urea reduction ratio statistically distinguished cachectic patients (P = 0.001). However, measures of weight, BMI, MUAMC, HGS, CRP, ERI and FACIT tended to worsen in cachectic patients. Conclusion Globally, cachexia is a severe but frequently underrecognized problem. This is the first study to apply the defined characteristics of cachexia to a representative sample of patients receiving HD. Further, more extensive studies are required to establish a phenotype of cachexia in advanced CKD.