Wasting in Chronic Kidney Disease – a Complex Issue

Adrian David Slee, Joanne Reid


Chronic kidney disease (CKD) has become a global health burden and is associated with increased morbidity and mortality. In particular, wasting is highly prevalent in later stages of the illness with muscle loss being a common problem. The aetiology and progression of this wasting is complex and multiple states have been identified linked to wasting in CKD. These include: ‘malnutrition’, ‘disease-related malnutrition’, ‘protein-energy wasting’, ‘cachexia’, ‘sarcopenia’, ‘frailty’ and ‘muscle wasting’. The purpose of this paper is to review these terms in the context of CKD. Common features include weight loss, loss of muscle mass and muscle function principally driven by CKD disease specific factors and inflammatory mediators. Disease-related malnutrition would appear to be a more appropriate term for CKD than malnutrition as it take in to consideration disease specific factors such as inflammation for example.  Frailty is commonly associated with age-related decline in physiological function. Development of novel screening tools measuring across multiple domains of nutritional status, muscle and physical function may be useful in CKD. Research into potential treatments are currently underway with focus on multi-modal therapies including nutrition, resistance training and anabolic drugs such as myostatin blockade and selective androgen receptor modulators. A better understanding of different states and terms may help guide assessment and treatment opportunities for patients.

Full Text:




Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, et al. GBD 2015 mortality and causes of death collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016;388:1459–544.

Fraser S, and Taal M. Multimorbidity in people with chronic kidney diease: implications for outcomes and treatment. Current Opinion in Nephrology and Hypertension 2016;25(6):465-472.

Fouque D, Kalantar-Zadeh K, Kopple J, Cano N, Chauveau P, Cuppari L, et al. A proposed nomenclature and diagnostic criteria for protein–energy wasting in acute and chronic kidney disease. Kidney International 2007;73(4):391–398.

Carrero JJ, Stenvinkel P, Cuppari L, Ikizler TA, Kalantar-Zadeh K, Kaysen G, et al. Etiology of the protein-energy wasting syndrome in chronic kidney disease: A consensus statement from the international society of renal nutrition and metabolism (ISRNM). Journal of Renal Nutrition 2013;23(2):77–90.

Baracos V and Kazemi-Bajestani SM. Clinical outcomes related to muscle mass in humans with cancer and catabolic illnesses. Int J Biochem Cell Biol 2013;45 (10):2302-2308.

Anker SD, Coats AJS, Morley JE, Rosano G, Bernabei R, von Haehling S and Kalantar-Zadeh, K. (2014) Muscle wasting disease: A proposal for a new disease classification. Journal of Cachexia, Sarcopenia and Muscle 2014;5(1):1–3.

Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56(3):146-156.

Cederholm T, Bosaeus I, Barazzoni R, Bauer J, Van Gossum A, Klek S, et al. Diagnostic criteria for malnutrition – an ESPEN consensus statement. Clinical Nutrition 2015;34(3):335–340.

Jensen GL, Mirtallo J, Compher C, Dhaliwal R, Forbes A, Grijalba RF, et al. Adult starvation and disease-related malnutrition: A proposal for etiology-based diagnosis in the clinical practice setting from the international consensus guideline committee. Clinical Nutrition 2010;29(2):151–153.

Ikizler TA, Cano NJ, Franch H, Fouque D, Himmelfarb J, Kalantar-Zadeh K, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: A consensus statement by the international society of renal nutrition and metabolism. Kidney International 2013;84(6):1096–1107.

Park J, Ahmadi S, Streja E, Molnar M, Flegal K, Gillen D, et al. Obesity Paradox in End-Stage Kidney Disease Patients. Progress in Cardiovascular Diseases 2014;56(4):415-425.

Evans WJ, Morley JE, Argiles J, Bales C, Baracos V, Guttridge D, et al. Cachexia: A new definition. Clin Nutr 2008;27:793-799.

Seelaender M, Laviano A, Busquets S, Püschel G, Margaria T and Batista M. Inflammation in cachexia. Mediators Inflamm 2015:536954.

Chertow GM, Johansen KL, Lew N, Lazarus JM and Lowrie EG. Vintage, nutritional status, and survival in hemodialysis patients. Kidney International 2000;57(3):1176–1181.

Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: An international consensus. The Lancet Oncology 2011;12(5):489–495.

Mak RH, Ikizler AT, Kovesdy CP, Raj DS, Stenvinkel P, Kalantar-Zadeh K. Wasting in chronic kidney disease. J Cachexia Sarcopenia Muscle 2011;2:9–25.

Von Haehling S and Anker S. Treatment for cachexia: an overview of recent developments. JAMDA 2014;15:866-872.

Reid J, Noble HR, Porter S, Shields JS and Maxwell AP. A literature review of end-stage renal disease and cachexia: understanding experience to inform evidence-based healthcare. J Ren Care 2013;39(1):47-51.

Reid J, Noble HR, Slee A, Davenport A, Farrington K, Fouque D, et al. Distinguishing between cachexia, sarcopenia and protein energy wasting in end-stage renal disease patients on dialysis. Palliat Med Hosp Care Open J 2016;2(2):11-13.

Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: european consensus on definition and diagnosis: report of the european working group on sarcopenia in older people. Age and Ageing 2010;39(4):412–423.

Fielding R, Vellas B, Evans W, Bhasin S, Morley J, Newman A, et al. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. Journal of the American Medical Directors Association 2011;12(4):249-256.

Morley J, Anker S and von Haehling S. Prevalence, incidence, and clinical impact of sarcopenia: facts, numbers, and epidemiology-update 2014. Journal of Cachexia, Sarcopenia and Muscle 2014;5(4):253-259.

Cruz-Jentoft AJ, Kiessmwetter E, Drey M and Sieber CC. Nutrition, frailty, and sarcopenia. Aging Clin Exp Res 2017;29:43-48.

Malmstrom T, Miller D, Simonsick E, Ferrucci L and Morley J. SARC-F: a symptom score to predict persons with sarcopenia at risk for poor functional outcomes. Journal of Cachexia, Sarcopenia and Muscle 2015;7(1):28-36.

Moon SJ, Kim TH, Yoon SY, Chung JH and Hwang H-J. Relationship between stage of chronic kidney disease and sarcopenia in korean aged 40 years and older using the Korea national health and nutrition examination surveys (KNHANES IV-2, 3, and V-1, 2), 2008–2011. PLOS ONE 2015;10(6):e0130740.

Pereira R, Cordeiro A, Avesani C, Carrero J, Lindholm B, Amparo F, et al. Sarcopenia in chronic kidney disease on conservative therapy: prevalence and association with mortality. Nephrology Dialysis Transplantation 2015;30(10):1718-1725.

Souza V, Oliveira D, Barbosa S, Corrêa J, Colugnati F, Mansur H, et al. Sarcopenia in patients with chronic kidney disease not yet on dialysis: Analysis of the prevalence and associated factors. PLOS ONE 2017;12(4):e0176230.

Leenders M, Verdijk LB, van der Hoeven L, Adam JJ, van Kranenburg J, Nilwik R, et al. Patients with type 2 diabetes show a greater decline in muscle mass, muscle strength, and functional capacity with aging. J Am Med Dir Assoc 2013;14(8):585-592.

Hirai K, Ookawara S and Morishita Y. Sarcopenia and physical inactivity in patients with chronic kidney disease. Nephro-Urology Monthly 2016;8(3):e37443.

Cukor D, Peterson R, Cohen S and Kimmel P. Depression in end-stage renal disease hemodialysis patients. Nature Clinical Practice Nephrology 2006;2(12):678-687.

Moorthi R and Avin K. Clinical relevance of sarcopenia in chronic kidney disease. Current Opinion in Nephrology and Hypertension 2017;26(3):219-228.

Anker S, Morley J and von Haehling S. Welcome to the ICD-10 code for sarcopenia. Journal of Cachexia, Sarcopenia and Muscle 2016;7(5):512-514.

Landi F, Calvani R, Cesari M, Tosato M, Martone A, Bernabei R, et al. Sarcopenia as the biological substrate of physical frailty. Clinics in Geriatric Medicine 2015;31(3):367-374.

Wilhelm-Leen ER, Hall YN, Tamura MK, and Chertow GM. Frailty and chronic kidney disease: The third national health and nutrition evaluation survey. Am J Med 2009;122(7):664–671.

Musso C, Jauregui J and Macías Núñez J. (2015). Frailty phenotype and chronic kidney disease: a review of the literature. International Urology and Nephrology 2015;47(11):1801-1807.

Reese PP, Cappolad AR, Shults J, Townsend RR, Gadegbekuf C, Andersong C., et al. (2013) Physical performance and frailty in chronic kidney disease. Am J Nephrol 2013;38(4):307–315.

Walker S, Gill K, Macdonald K, Komenda P, Rigatto C, Sood M, et al. Association of frailty and physical function in patients with non-dialysis CKD: a systematic review. BMC Nephrology 2013;14(1):228.

Shen Z, Ruan Q, Yu Z and Sun Z. Chronic kidney disease-related physical frailty and cognitive impairment: A systemic review. Geriatrics & Gerontology International 2016;(4):529-544.

Foster R, Walker S, Brar R, Hiebert B, Komenda P, Rigatto C, et al. Cognitive impairment in advanced chronic kidney disease: The canadian frailty observation and interventions trial. American Journal of Nephrology 2016;44 (6):473–480.

Ebner N, Sliziuk V, Scherbakov N and Sandek A. Muscle wasting in ageing and chronic illness. ESC Heart Failure 2015;2(2):58–68.

Jeejeebhoy KN, Detsky AS and Baker JP. Assessment of nutritional status. JPEN 1990;14(5S):193-196.

Steiber A, Kalantar-Zadeh K, Secker D, McCarthy M, Sehgal A and McCann L. Subjective Global Assessment in chronic kidney disease: A review. Journal of Renal Nutrition 2004;14(4):191-200.

Campbell K, Ash S, Bauer J and Davies P. Evaluation of nutrition assessment tools compared with body cell mass for the assessment of malnutrition in chronic kidney disease. Journal of Renal Nutrition 2007;17(3):189-195.

Gurreebun F, Hartley G, Brown A, Ward M and Goodship T. Nutritional screening in patients on hemodialysis: is subjective global assessment an appropriate tool? Journal of Renal Nutrition 2007;17(2):114-117.

Kalantar-Zadeh K, Kopple J, Block G and Humphreys M. A Malnutrition-Inflammation Score is correlated with morbidity and mortality in maintenance hemodialysis patients. American Journal of Kidney Diseases 2001;38(6):1251-1263.

Obi Y, Qader H, Kovesdy C and Kalantar-Zadeh K. Latest consensus and update on protein-energy wasting in chronic kidney disease. Current Opinion in Clinical Nutrition and Metabolic Care 2015;18(3):254-262.

Bouillanne O, Morineau G, Dupont C, Colombel I, Vincent J-P, Nicolis I, et al. Geriatric Nutritional Risk Index: a new index for evaluating at-risk elderly medical patients. Am J Clin Nutr 2005;82:777–783.

Yamada K, Furuya R, Takita T, Maruyama Y, Yamaguchi Y, Ohkawa S, et al. Simplified nutritional screening tools for patients on maintenance hemodialysis. Am J Clin Nutr 2008;87(1):106-113.

Kutner N, Zhang R, Huang Y and Painter P. Gait speed and mortality, hospitalization, and functional status change among hemodialysis patients: a US renal data system special study. American Journal of Kidney Diseases 2015;66(2):297-304.

Roshanravan B, Robinson-Cohen C, Patel K, Ayers E, Littman A, de Boer I, et al. Association between physical performance and all-cause mortality in CKD. Journal of the American Society of Nephrology 2013;24(5):822-830.

Chang Y, Wu H, Guo H, Cheng Y, Tseng C, Wang M, et al. Handgrip strength is an independent predictor of renal outcomes in patients with chronic kidney diseases. Nephrology Dialysis Transplantation 2011;26(11):3588-3595.

Carrero JJ, Johansen KL, Lindholm B, Stenvinkel P, Cuppari L and Avesani C. M. Screening for muscle wasting and dysfunction in patients with chronic kidney disease. Kidney International 2016;90(1):53–66.

Landi F, Russo A, Liperoti R, Pahor M, Tosato M, Capoluongo E, et al. Midarm muscle circumference, physical performance and mortality: Results from the aging and longevity study in the Sirente geographic area (ilSIRENTE study). Clinical Nutrition 2010;29(4):441-447.

Noori N, Kopple J, Kovesdy C, Feroze U, Sim J, Murali S, et al. Mid-arm muscle circumference and quality of life and survival in maintenance hemodialysis patients. Clinical Journal of the American Society of Nephrology 2010;5(12):2258-2268.

Friedman A. Omega-3 fatty acid supplementation in advanced kidney disease. Seminars in Dialysis 2010;23(4):396-400.

Hu J, Liu Z and Zhang H. Omega-3 fatty acid supplementation as an adjunctive therapy in the treatment of chronic kidney disease: a meta-analysis. Clinics 2017;72(1):58-64.

Wu H, Xia Y, Jiang J, Du H, Guo X, Liu X, et al. Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: A systematic review and meta-analysis. Archives of Gerontology and Geriatrics 2015;61(2):168-175.

Abramowitz M, Melamed M, Bauer C, Raff A and Hostetter T. Effects of oral sodium bicarbonate in patients with CKD. Clinical Journal of the American Society of Nephrology 2013;8(5):714-720.

Pfeifer M, Begerow B and Minne H. Vitamin D and muscle function. Osteoporosis International 2002;13(3):187-194.

Williams S, Malatesta K and Norris K. Vitamin D and chronic kidney disease. Ethn Dis 2009;19(4 Suppl 5):S5-8-11.

Taskapan H, Baysal O, Karahan D, Durmus B, Altay Z, Ulutas O. Vitamin D and muscle strength, functional ability and balance in peritoneal dialysis patients with vitamin D deficiency. Clin Nephrol 2011;76(2):110–116.

Morley JE, Argiles JM, Evans WJ, Bhasin S, Cella D, Deutz NE, et al. Nutritional recommendations for the management of sarcopenia. J Am Med Dir Assoc 2010;11:391–396.

Tieland M, van de Rest O, Dirks ML, van der Zwaluw N, Mensink M, van Loon LJ, et al. Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc 2012;13:720–726.

Boirie Y. Fighting sarcopenia in older frail subjects: protein fuel for strength, exercise for mass. J Am Med Dir Assoc 2013;14:140–143.

Eustace JA, Coresh J, Kutchey C, Te PL, Gimenez LF, Scheel PJ, et al. Randomized double-blind trial of oral essential amino acids for dialysis-associated hypoalbuminemia. Kidney Int 2000;57:2527–2538.

Vilay AM, Mueller BA. Intradialytic oral nutritional supplements improve quality of life. Am J Kidney Dis 2013;61:349.

Jadeja Y and Kher V. Protein energy wasting in chronic kidney disease: An update with focus on nutritional interventions to improve outcomes. Indian Journal of Endocrinology and Metabolism 2012;16(2):246-251.

Sabatino A, Regolisti G, Karupaiah T, Sahathevan S, Sadu Singh BK, Khor BH, et al. Protein-energy wasting and nutritional supplementation in patients with end-stage renal disease on hemodialysis. Clinical Nutrition 2017;36(3):663-671.

Watson E, Greening N, Viana J, Aulakh J, Bodicoat D, Barratt J, et al. Progressive resistance exercise training in CKD: A feasibility study. American Journal of Kidney Diseases 2015;66(2):249-257.

Cheema B, Chan D, Fahey P and Atlantis E. Effect of progressive resistance training on measures of skeletal muscle hypertrophy, muscular strength and health-related quality of life in patients with chronic kidney disease: a systematic review and meta-analysis. Sports Medicine 2014;44(8):1125-1138.

Cesari M, Fielding R, Benichou O, Bernabei R, Bhasin S, Guralnik JM, et al. Pharmacological interventions in frailty and sarcopenia: report by the international conference on frailty and sarcopenia research task force. J Frailty Aging 2015;4(3):114-120.

Gullett NP, Hebbar G and Ziegler TR. Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting Am J Clin Nutr 2010;91(suppl):1143S–7S.

DOI: http://dx.doi.org/10.17987/jcsm-cr.v3i2.63


  • There are currently no refbacks.