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| CLASSROOM READING |
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| Year : 2019 | Volume
: 5
| Issue : 3 | Page : 64-66 |
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Pathophysiology of protein–energy wasting
Smita Divyaveer
Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| Date of Submission | 26-Dec-2019 |
| Date of Acceptance | 10-Jan-2020 |
| Date of Web Publication | 17-Feb-2020 |
Correspondence Address:
Dr. Smita Divyaveer
Postgraduate Institute of Medical Education and Research, Chandigarh
India
 Source of Support: None, Conflict of Interest: None  | 4 |
DOI: 10.4103/jrnm.jrnm_59_19
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 |
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
Click here to view |
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]
Click here to view |
| Decreased Protein and Energy Intake | |  |
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]
Summary
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.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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[Figure 1]
[Table 1]
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