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Table of Contents
Year : 2019  |  Volume : 5  |  Issue : 3  |  Page : 64-66

Pathophysiology of protein–energy wasting

Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Submission26-Dec-2019
Date of Acceptance10-Jan-2020
Date of Web Publication17-Feb-2020

Correspondence Address:
Dr. Smita Divyaveer
Postgraduate Institute of Medical Education and Research, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jrnm.jrnm_59_19

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Malnutrition refers to abnormalities induced by an inadequate diet, whereas wasting refers to abnormalities that cannot be corrected solely by increasing the diet.[6] Although these entities are different in their etiopathogenesis somewhat, both share some common features such as low serum albumin, prealbumin, and body mass index. Although these entities are different in their etiopathogenesis somewhat, both share some common features such as low serum albumin, prealbumin, and body mass index. Hence, subjective and objective assessment of PEW and intervention for correctible factors must be carried out routinely.

Keywords: Hypoalbuminemia inflammation, malnutrition–inflammation atherosclerosis, renal dysfunction

How to cite this article:
Divyaveer S. Pathophysiology of protein–energy wasting. J Renal Nutr Metab 2019;5:64-6

How to cite this URL:
Divyaveer S. Pathophysiology of protein–energy wasting. J Renal Nutr Metab [serial online] 2019 [cited 2023 May 28];5:64-6. Available from: http://www.jrnm.in/text.asp?2019/5/3/64/278612

Protein–energy wasting (PEW) and the scientific evidence for its association with alteration of immunity, infections, and, therefore, bad outcomes has been known since quite some decades now. Initially, dietary insufficiency/deficiency and malignancies were the identified causes of malnutrition; however, subsequently, it was also found to be associated with nonmalignant chronic diseases.[1],[2],[3] Evidence of wasting can be present in approximately 18–75% of patients undergoing dialysis using nutritional assessment using classic measures or surveys.[3] These syndromes have been termed in various ways previously eg. uremic malnutrition, uremic (renal) cachexia, protein–energy malnutrition, malnutrition–inflammation atherosclerosis syndrome or malnutrition–inflammation complex (or cachexia) syndrome. The International Society of Renal Nutrition and Metabolism (ISRNM)[4],[5] has reviewed literature and published consensus draft that has given standard terminologies and definitions related to wasting, cachexia, malnutrition, and inflammation in CKD and AKI.

Malnutrition refers to abnormalities induced by an inadequate diet, whereas wasting refers to abnormalities that cannot be corrected solely by increasing the diet.[6] Although these entities are different in their etiopathogenesis somewhat, both share some common features such as low serum albumin, prealbumin, and body mass index. Furthermore, “malnutrition” may indicate both undernutrition and overnutrition. Wasting and not malnutrition has been associated with bad cardiovascular outcomes in end-stage renal disease. Despite adequate nutrient intake, inflammation and renal dysfunction which in turn cause endocrine disbalance impair protein anabolism [Figure 1].
Figure 1: Pathophysiological processes and factors causing protein energy malnutrition in kidney diseases

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Kidney disease wasting is also a rather vague term and can lead to misinterpretation. Malnutrition–inflammation complex syndrome and MIA have been proposed as syndromes due to close association of the involved entities.[7],[8],[9],[10],[11]

Protein–energy wasting (PEW) is the state of decreased body stores of protein and energy fuels (that is, loss of both body protein and fat masses).[4] Cachexia is the extreme spectrum of PEW, and is usually associated with alterations at multiple levels i.e. physiological, metabolic, psychological, and immunological disorders.[4],[5]

PEW in kidney diseases is likely multifactorial. Dietary inadequacy alone does not explain the components PEW observed in CKD. [Table 1] shows the major causative factors for PEW in CKD.
Table 1: Causes of protein-energy wasting in chronic kidney disease[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14]

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  Decreased Protein and Energy Intake Top

Dietary restrictions without appropriate supplementation and monitoring of nutrition status can lead to both protein and energy malnutrition. Anorexia can be associated with metabolic alterations and increased cytokines due to uremia itself, gastrointestinal complications, mechanical factors in peritoneal dialysis. CKD patients also often have xerostomia and dysgeusia, which may contribute to reduced dietary intake of nutrients. Depression is another correctible cause of decreased dietary intake. Moreover, certain medications, such as phosphate binders, can impair nutrient absorption.[12],[13],[14]

Hypermetabolism has been observed in CKD in the form of increased resting energy expenditure and is a result of multiple factors as mentioned above. Other factors such as decreased anabolism due to endocrine abnormalities as mentioned above, including possible role of hyperglucagonemia, hyperparathyroidism, chronic metabolic acidosis, and the presence of other chronic comorbidities, also alter the balance of metabolism.

Inflammatory markers are upregulated in CKD; C-reactive protein in particular has been found to be elevated in a significantly high percentage of CKD patients.[1] Other markers are interleukin (IL)-6 and low serum albumin. Some studies have shown tumor necrosis factor (TNF)-alpha to be to mediate proteolysis and muscle wasting. Experimental studies have shown that PEW induces a low-grade proinflammatory state involving increase in IL-1, IL-6, TNF, and α1-acid glycoprotein. The exact mechanism of how inflammation contributes to PEW is not clear completely.[15] Proinflammatory cytokine levels and oxidative stress appear to contribute to PEW. Other factors that possibly contribute to inflammation include volume overload with endotoxinemia, advanced glycation end products[16],[17] resulting from carbonyl stress, decreased antioxidants, underrecognized periodontal and persistent infections, gut dysbiosis, and ongoing inflammation in a failed allograft. Inflammation has been identified as playing a key role in atherosclerotic cardiovascular disease (CVD). Atherosclerosis is an established risk factor for CVD mortality. Moreover, inflammation is associated with congestive heart failure.

Finally, the procedure of dialysis itself via various ways/mechanisms such as upregulation of inflammation due to less biocompatible membranes, poor quality of dialysis water and backfiltration, and the presence of graft or catheter-related bacteremia contribute to muscle catabolism. Other contributory factors are inadequate dialysis, loss of protein (particularly in peritoneal dialysis patients), and peritonitis.[3],[13]


Multifactorial association and myriad consequences which cause protein–energy malnutrition in uremic milieu include anorexia malnutrition inflammation metabolic acidosis hormonal imbalance increased level of leptin, decreased ghrelin, hypoalbuminemia, anemia functional incapacitance, and poor quality of life.

Due to interrelated mechanisms of malnutrition, infection, inflammation which are all involved in pathogenesis of PEW as a syndrome, and some of these along with atherosclerosis create a vicious circle ultimately leading to worse outcomes in terms of morbidity and mortality in both dialysis dependent and nondialysis dependent CKD. PEW is likely the plausible reason of reverse epidemiology seen in CKD. PEW also tends to worsen with deteriorating kidney function.[18]

Hence, assessment of nutritional status with tools, subjective and objective assessment of PEW and intervention for correctible factors must be carried out routinely.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Keusch GT. The history of nutrition: Malnutrition, infection and immunity. J Nutr 2003;133:336S-40S.  Back to cited text no. 1
Akner G, Cederholm T. Treatment of protein-energy malnutrition in chronic nonmalignant disorders. Am J Clin Nutr 2001;74:6-24.  Back to cited text no. 2
Kopple JD. McCollum Award Lecture, 1996: Protein-energy malnutrition in maintenance dialysis patients. Am J Clin Nutr 1997;65:1544-57.  Back to cited text no. 3
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 Int 2008;73:391-8.  Back to cited text no. 4
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). J Ren Nutr 2013;23:77-90.  Back to cited text no. 5
Stenvinkel P, Heimbürger O, Lindholm B. Wasting, but not malnutrition, predicts cardiovascular mortality in end-stage renal disease. Nephrol Dial Transplant 2004;19:2181-3.  Back to cited text no. 6
Mitch WE. Malnutrition: A frequent misdiagnosis for hemodialysis patients. J Clin Invest 2002;110:437-9.  Back to cited text no. 7
Stenvinkel P. Inflammation in end-stage renal disease-a fire that burns within. In: Cardiovascular Disorders in Hemodialysis. Contributions to nephrology, v. 149. Auhtors C Ronco; Alessandra Brendolan; Nathan W Levin Basel ; New York : Karger, ©2005. Karger Publishers; 2005. p. 185-99.  Back to cited text no. 8
Nitta K, Tsuchiya K. Recent advances in the pathophysiology and management of protein-energy wasting in chronic kidney disease. Ren Replace Ther 2016;2:4.  Back to cited text no. 9
Pecoits-Filho R, Lindholm B, Stenvinkel P. The malnutrition, inflammation, and atherosclerosis (MIA) syndrome – The heart of the matter. Nephrol Dial Transplant 2002;17 Suppl 11:28-31.  Back to cited text no. 10
Kalantar-Zadeh K, Ikizler TA, Block G, Avram MM, Kopple JD. Malnutrition-inflammation complex syndrome in dialysis patients: Causes and consequences. Am J Kidney Dis 2003;42:864-81.  Back to cited text no. 11
Chazot C. Why are chronic kidney disease patients anorexic and what can be done about it? Semin Nephrol 2009;29:15-23.  Back to cited text no. 12
Neyra R, Chen KY, Sun M, Shyr Y, Hakim RM, Ikizler TA. Increased resting energy expenditure in patients with end-stage renal disease. JPEN J Parenter Enteral Nutr 2003;27:36-42.  Back to cited text no. 13
Kalantar-Zadeh K. Inflammatory marker mania in chronic kidney disease: Pentraxins at the crossroad of universal soldiers of inflammation. Clin J Am Soc Nephrol 2007;2:872-5.  Back to cited text no. 14
Tonelli M, Sacks F, Pfeffer M, Jhangri GS, Curhan G, Cholesterol and Recurrent Events (CARE) Trial Investigators. Biomarkers of inflammation and progression of chronic kidney disease. Kidney Int 2005;68:237-45.  Back to cited text no. 15
Mitch WE, Goldberg AL. Mechanisms of muscle wasting – The role of the ubiquitin–proteasome pathway. N England J Med 1996;335:1897-905.  Back to cited text no. 16
Ling PR, Smith RJ, Kie S, Boyce P, Bistrian BR. Effects of protein malnutrition on IL-6-mediated signaling in the liver and the systemic acute-phase response in rats. Am J Physiol Regul Integr Comp Physiol 2004;287:R801-8.  Back to cited text no. 17
Kovesdy CP, Kalantar-Zadeh K. Why is protein-energy wasting associated with mortality in chronic kidney disease? Semin Nephrol 2009;29:3-14.  Back to cited text no. 18


  [Figure 1]

  [Table 1]

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