Wasting in chronic kidney disease

Abstract

Wasting/cachexia is prevalent among patients with chronic kidney disease (CKD). It is to be distinguished from malnutrition, which is defined as the consequence of insufficient food intake or an improper diet. Malnutrition is characterized by hunger, which is an adaptive response, whereas anorexia is prevalent in patients with wasting/cachexia. Energy expenditure decreases as a protective mechanism in malnutrition whereas it remains inappropriately high in cachexia/wasting. In malnutrition, fat mass is preferentially lost and lean body mass and muscle mass is preserved. In cachexia/wasting, muscle is wasted and fat is relatively underutilized. Restoring adequate food intake or altering the composition of the diet reverses malnutrition. Nutrition supplementation does not totally reverse cachexia/wasting. The diagnostic criteria of cachexia/protein-energy wasting in CKD are considered. The association of wasting surrogates, such as serum albumin and prealbumin, with mortality is strong making them robust outcome predictors. At the patient level, longevity has consistently been observed in patients with CKD who have more muscle and/or fat, who report better appetite and who eat more. Although inadequate nutritional intake may contribute to wasting or cachexia, recent evidence indicates that other factors, including systemic inflammation, perturbations of appetite-controlling hormones from reduced renal clearance, aberrant neuropeptide signaling, insulin and insulin-like growth factor resistance, and metabolic acidosis, may be important in the pathogenesis of CKD-associated wasting. A number of novel therapeutic approaches, such as ghrelin agonists and melanocortin receptor antagonists are currently at the experimental level and await confirmation by randomized controlled clinical trials in patients with CKD-associated cachexia/wasting syndrome.

Fig. 1

Conceptual representation of the definition: cachexia results from adaptation to an underlying illness such as cancer or CKD. The illness creates an environment that may be characterized by inflammation, loss of appetite (anorexia), low levels of anabolic hormones, and anemia. Decreased food intake and anorexia result in loss of body and muscle mass. In addition, inflammation, insulin resistance, and low levels of anabolic hormones result in muscle wasting. Reproduced with permission from [21]

Fig. 2

Schematic representation of the causes and manifestations of the protein–energy wasting syndrome in chronic kidney disease. Reprinted with permission from [22]

Fig. 3

Orexigenic and anorexigenic mechanisms controlling energy homeostasis in CKD. Reprinted with permission from [7]

Fig. 4

Pathophysiology of muscle wasting in CKD. Reprinted with permission from [78]

Fig. 5

Impact of nutritional supplementation on energy homeostasis in experimental CKD. N = 5/6 nephrectomized, S sham-operated controls, Supp mice given nutritional supplements by gavage. Modified from data published in [4, 57]