Journal of Cachexia, Sarcopenia and Muscle (JCSM) - Abstract
Volume 2, Number 1, Page 9 - 25
Wasting in chronic kidney disease
Robert H. Mak, Alp T. Ikizler, Csaba P. Kovesdy, Dominic S. Raj, Peter Stenvinkel, et al.
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.
Sources of Funding RHM is supported by National Institutes of Health (NIH), National Institute of Diabetes, Digestive and Kidney Disease (NIDDK) grant U01-DK 03-012, and investigator-initiated grants from the Cystinosis Foundation and Abbott Inc.
TAI is supported by NIH, NIDDK grant K24 DK77875. KKZ is supported by NIH, NIDDK grant R01-DK078106-01, R21-DK078012, and R21-DK077341, and a philanthropist grant from Mr. Harold Simmons.
CPK is supported by NIH, NIDDK grant R01-DK078106-01. CPK is an employee of the US Dept of Veterans Affairs.
DSR is supported by NIH NIDDK grant R01-DK073665-01A1.
PS is supported by the Swedish Medical Research Council.
Mak RH, Ikizler AT, Kovesdy CP, Raj DS, Stenvinkel P, Kalantar-Zadeh K. Wasting in chronic kidney disease. J Cachex Sarcopenia Muscle 2011;1:9-25.