In the originally published version of thismanuscript, amendments made during the proofing stage were not applied and have been listed in this erratum. Upon the original publication, there was an error in the spelling of author Kamyar Kalantar-Zadeh’s surname. Upon the original publication, the ORCID ID for authors Andrew Davenport and Helen Noble were incorrectly added to the author list. These have now been deleted. Upon the original publication, the Twitter handle of some authors were added to the Corresponding author information in error. These have now been deleted. Upon the original publication, the following sentence in the “Results” line in the Abstract should read: “A total of 106 patients (30 females and 76 males) were recruited with a mean age of 67.6 years.”. Upon the original publication, the “Materials andMethods” section had the following errors: In the first paragraph, the following sentence should read: “...between September 2017 and April 2019.”. In the second paragraph, the following sentence should read: “A single researcher carried out all assessments.”. Under the “Musclemass (MUAMC)” heading, the following sentence should read: “Suitable cut-point values designated the 5th percentile as an appropriate cut-point for lowMUAMC using normative values (i.e. <23.8cmfor males and <18.4cm for females) [11, 12].”. Under the “Analysis” heading, the following sentence should read: “Dichotomized values were compared using the X2 test.”. Upon the original publication, the following text in the Results section, under the “Longitudinal results” heading should read: “showed a significant main effect of time on HGS (P<0.001)”. Upon the original publication, the following sentence in the Discussion section, under the “Cachectic phenotype” heading should read: “Therefore the cut-off value for CRP levels in an ESRD population needs to be revised to a level >5mg/L.”. Upon the original publication, the following text in the Funding section should read: “Public Health Agency Northern Ireland”. Upon the original publication, within the reference section, the following citation (11) should refer to: “StosovicM, StanojevicM, Sanja Simic-Ogrizovic S, et al. The predictive value of anthropometric parameters onmortality in haemodialysis patients. Nephrol Dial Transplant 2011; 26: 1367–1374.”. These errors have now been corrected online. The publisher apologizes for the errors.

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.

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 67.6 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. >5% for >6 months) or BMI <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). 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.

AbstractObjectivesMalnutrition 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.MethodsA 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.ResultsThere was no significant relationship between FAACT and albumin levels ( = 0.14;  = 0.16) or BMI ( = 0.28;  = .19). However, there was a moderate and significant negative correlation between FAACT and CRP levels ( = 0.31;  < 0.001) indicating an inverse relationship between appetite (e.g., decreased FAACT score) and CRP levels (e.g., higher inflammation).ConclusionsWe 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 SourcesThis 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).

Through an international consortium, we have collected 37 tau- and TAR DNA-binding protein 43 (TDP-43)-negative frontotemporal lobar degeneration (FTLD) cases, and present here the first comprehensive analysis of these cases in terms of neuropathology, genetics, demographics and clinical data. 92% (34/37) had fused in sarcoma (FUS) protein pathology, indicating that FTLD-FUS is an important FTLD subtype. This FTLD-FUS collection specifically focussed on aFTLD-U cases, one of three recently defined subtypes of FTLD-FUS. The aFTLD-U subtype of FTLD-FUS is characterised clinically by behavioural variant frontotemporal dementia (bvFTD) and has a particularly young age of onset with a mean of 41 years. Further, this subtype had a high prevalence of psychotic symptoms (36% of cases) and low prevalence of motor symptoms (3% of cases). We did not find FUS mutations in any aFTLD-U case. To date, the only subtype of cases reported to have ubiquitin-positive but tau-, TDP-43- and FUS-negative pathology, termed FTLD-UPS, is the result of charged multivesicular body protein 2B gene (CHMP2B) mutation. We identified three FTLD-UPS cases, which are negative for CHMP2B mutation, suggesting that the full complement of FTLD pathologies is yet to be elucidated.