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Patients with end-stage renal disease (ESRD) receiving dialysis can have altered nutritional status and body composition due to dietary restrictions, level of physical activity, co-morbidities, metabolic alterations and inflammation.1 As such, weight loss or wasting is common among this population with up to 75% of adults with ESRD undergoing maintenance dialysis displaying some evidence of wasting.
Editorial Distinguishing Between Cachexia, * *Corresponding author Sarcopenia and Protein Energy Wasting Joanne Reid, PhD Reader in Cancer Nursing School of Nursing and Midwifery in End-Stage Renal Disease Patients on Queen’s University Belfast Room 06.312, Medical Biology Centre Dialysis Block 97 Health Sciences 97 Lisburn Road Belfast BT9 7BL, UK 1* 1 2 3 00442890972459 Joanne Reid, PhD ; Helen R. Noble, PhD ; Adrian Slee, PhD ; Andrew Davenport, MD ; Tel.
4 5 6 E-mail: j.reid@qub.ac.uk Ken Farrington, MD4; Denis Fouque, PhD5; Kamyar Kalantar-Zadeh, PhD6; Sam Porter, 7 8 9 PhD ; David Seres, MD ; Miles D. Witham, PhD ; Alexander P. Maxwell, PhD Volume 2 : Issue 2 1 School of Nursing and Midwifery, Queen’s University Belfast, Belfast, UK Article Ref. #: 1000PMHCOJ2e004 2Lecturer in Nutrition, London South Bank University, UK 3Consultant Nephrologist, Royal Free Hospital, 103 Borough Rd, London SE1 0AA, UK Article History 4 Consultant Nephrologist, East and North Hertfordshire Trust, Coreys Mill Ln, Stevenage st Received: November 21st, 2016 SG1 4AB, UK rd Accepted: November 23rd, 2016 5 Professor of Nephrology, Université de Lyon, 92 Rue Pasteur, 69007 Lyon, France th Published: November 25th, 2016 6 Chief, Division of Nephrology and Hypertension, Professor of Medicine, Pediatrics and Public Health, University of California USA, CA, USA 7Professor of Nursing Sociology, Department of Social Sciences and Social Work, Citation Bournemouth University, UK Reid J, Noble HR, Slee A, et al.
Distinguishing between cachexia, 8Director of Medical Nutrition and Associate Professor of Medicine, Columbia University, New sarcopenia and protein energy wast- York, USA ing in end-stage renal disease pa- 9 Clinical Reader in Ageing and Health, University of Dundee, Nethergate, Dundee DD1 4HN, tients on dialysis. Palliat Med Hosp UK Care Open J. 2016; 2(2): e11-e13.
doi: 10.17140/PMHCOJ-2-e004 10Consultant Nephrologist, Professor of Renal Medicine, Belfast Health and Social Care Trust, UK; School of Medicine, Queen’s University Belfast, UK Patients with end-stage renal disease (ESRD) receiving dialysis can have altered nutritional status and body composition due to dietary restrictions, level of physical activity, co-morbidities, metabolic alterations and inflammation.1 As such, weight loss or wasting is common among this population with up to 75% of adults with ESRD undergoing maintenance dialysis displaying some evidence of wasting.2 There are several forms of loss of lean muscle mass or wasting in ESRD, including ‘protein energy wasting’, ‘cachexia’, and ‘age-related sarcopenia’ and these terms are often used interchangeably alongside ‘malnutrition’ in current care. Limited understanding of the differences between such terms is arguably a barrier to ac- curate recognition and management of these disorders in patients with ESRD. For instance, a recent European study of over 700 dietetic participants concluded that only 13% of health care professionals who could differentiate between malnutrition, starvation, cachexia and sarcope- nia.3 Such knowledge is pertinent as for example, loss of muscle mass is a key feature in both sarcopenia and cachexia, but most patients with sarcopenia are not cachectic,4 as muscle wast- ing occurs with aging.
Research has informed a disease specific definition (and associated diagnostic criteria) for protein energy wasting (PEW) in renal disease, and while cachexia in ESRD is seen as the Copyright 5 severe form of PEW, there remains no consensus definition or diagnostic criteria to differenti- ©2016 Reid J. This is an open ac- ate between PEW and cachexia. What distinguishes PEW from cachexia is that the latter relates cess article distributed under the to only severe forms of metabolic depletion. However, PEW can refer to mild reduction of lean Creative Commons Attribution 4.0 6 International License (CC BY 4.0), muscle and depletion of energy stores. Alongside, the lack of disease specific definition or which permits unrestricted use, diagnostic criteria for cachexia, there is also no such disease specific criterion for sarcopenia distribution, and reproduction in in renal disease. The evidence-based development of these terms is essential to enable health any medium, provided the original care professionals to clearly identify and differentiate between such conditions. This greater work is properly cited.
understanding of the difference and interplay between cachexia, PEW and sarcopenia in ESRD has the potential to inform the development and testing of targeted novel therapeutic treatments aimed at reducing morbidity and mortality.7 Significant progress has been made defining cachexia and its associated clinical characteristics in patients with cancer. An agreed definition and classification of cancer cachexia8 has contributed to enhanced standardization of screening, staging assessment and management. This is a model that could be applied to cachexia in other chronic conditions, such as ESRD. Reflecting the current evidence base, Table 1 outlines the characteristics of age-related sarcopenia, cachexia in chronic 5,9-11 illness, and PEW in renal disease. These characteristics and associated pathologies are reviewed elsewhere in the literature, and while the diagnostic criteria share similarities they are not identical. For example, weight loss is part of the definition of both cachexia in chronic illness and PEW in renal disease, but the duration of the weight loss differs (weight loss of 5% over 6 months in cachexia as opposed to 5% over 3 months in PEW). Additionally, the diagnostic criteria for cachexia in chronic illness empha- sizes lean mass functionality (decreased muscle strength and fatigue), which is also common in sarcopenia of old age, although the defining characteristics of sarcopenia emphasize the importance of gait speed which cachexia does not. Furthermore, anaemia is considered a feature of cachexia in chronic illness, but not of PEW in renal disease or sarcopenia of old age. 9 10 5,11 Sarcopenia of old age Cachexia in chronic illness Protein energy wasting in renal disease Oedema-free “unintentional” weight loss of at least 5% in 12 months or less in the presence of Unintentional weight loss over time: 5% over 3 Not stated, but weight gain is underlying illness. months or 10% over 6 months.
expected in obese sarcopenia (i) Weight whereas weight loss can occur In cases where weight loss cannot be documented, Oedema-free BMI<23 kg/m for example, otherwise 2 a BMI<18.5 kg/m or a drop from higher BMI to a post-dialysis dry weight.
Serum albumin<3.8 g/dl (bromocresol green).
Serum prealbumin (transthyretin)<30 mg/dL (for Increased inflammatory markers CRP (>3.0 mg/L), Not stated, but it is expected maintenance dialysis patients only; levels may IL-6>3.0 pg/mL).
(ii) Biochemistry that serum creatinine relative to vary according to GFR level for patients with Anaemia (<10 g/dL).
Low serum albumin (<3.5 g/dl BGG or <3.2 BCP) Serum cholesterol<100 mg/dL Total body fat percentage<10%.
Reduced mid-arm muscle circumference area - Low fat-free mass index.
Low muscle mass<7.23-7.26 kg/ reduction >10% in relation to 50th percentile of 2 2 Lean tissue depletion i.e. mid upper arm muscle (iii) Muscle and/or m for men and<5.5-5.67 kg/m th reference population.
circumference<10 percentile for age and gender); fat mass for women using appendicular Muscle wasting: reduced muscle mass 5% over 2 12 appendicular skeletal muscle index by DEXA <5.45 lean tissue/height by DEXA 2 2 3 months or 10% over 6 months.
Indirect measure of muscle mass, such as serum creatinine.
Low muscle strength, handgrip (iv) Muscle strength strength<20 kg women and<30 Decreased muscle strength (lowest tertile). Not stated kg men.
Presence of fatigue - defined as physical and/or Gait speed<0.8 metres per mental weariness, resulting from exertion; an inability (v) Functionality Not stated second. to continue exercise at the same intensity with a resultant deterioration in performance.
Unintentional low dietary protein intake<0.80 g/ kg/day for at least 2 months for dialysis patients Not stated, but often some Anorexia.
or<0.6 g/kg/day for patients with CKD stages 2-5.
(vi) Dietary intake decline in appetite and/or protein Limited food intake (i.e. total energy intake<20 kcal/ Unintentional low dietary energy intake<25 Kcal/ and energy is observed. kg /day; <70% of usual food intake) or poor appetite.
Person must have at least three out of the four Person must have column iii plus Person must have column i plus three of the Diagnosis columns i,ii,iii and vi and at least one test from column iv or v. remaining five columns ii,iii,iv,v,or vi.
As seen in Table 1, there are both variations and commonalities in the known clinical characteristics of sarcopenia, cachexia and PEW in a renal population. This may be reflective of the poly-symptomatic nature of ESRD. However, it makes the diagnosis of any of the three conditions more complex. Effectively distinguishing between these three conditions in ESRD is important, ac- knowledging that elements of sarcopenia and PEW may be present in cachexia, as interventional strategies may be very different for each. Work on delineating key clinical characteristics of PEW in renal disease has progressed extensively13 and cachexia is viewed as a severe form of PEW.5 However, the diagnostic criteria for cachexia in ESRD, as opposed to PEW, have not been agreed. This is significant as cachexia may involve additional metabolic abnormalities that are potentially amenable to therapeutic intervention. What should the next steps be? Adoption of a disease-specific definition of cachexia in ESRD would contribute to standard- ization of screening, assessment and management strategies that are aimed at improving morbidity and mortality in these patients. Such a definition needs to be derived in such a way to distinguish cachexia from both sarcopenia and PEW, should define a popula- tion group with a different prognosis from PEW, and needs to reflect our understanding of the pathophysiology (particularly the role of inflammation) of cachexia in other conditions such as cancer, heart failure and COPD. Such a definition would greatly facilitate 14,15 screening, diagnosis and development of treatments for this life-limiting complication of end stage renal disease.