Nutrition and Chronic Kidney Disease

Denis Fouque; Solenne Pelletier; Denise Mafra; Philippe Chauveau


Kidney Int. 2011;80(4):348-357. 

In This Article

Protein–Energy Wasting: How to Monitor Nutritional Risks and Improve Outcome?

One of the major side effects of kidney disease is the subtle development of anorexia and the concurrent reduction of protein–energy intake, already present at stage III of CKD[48] and during dialysis.[49–51] A number of orexigenic or anorexigenic hormone dysregulations (leptin, ghrelin, peptide YY, and obestatin) have been proposed to explain anorexia in healthy adults and patients.[52–54] Administering recombinant ghrelin during 7 days has been showed to increase meal energy intake by ~25% in malnourished hemodialysis patients.[55] Interestingly, Cheung et al. suggested a dysfunction of hypothalamic appetite-regulating sensors, such as the melanocortin-4 receptor.[56,57] Chronic renal failure mice knockout for this receptor ate normally, whereas their wild-type melanocortin-4 receptor counterparts severely reduced their food intake as a response to kidney failure.[56] When a melanocortin-4 receptor antagonist (such as NBI-12i) was administered to uremic mice, they gained lean and fat mass while lowering their energy expenditure, resulting in a net nutritional improvement. These findings may represent an interesting field to explore in order to improve patients appetite and food intake.

Growth hormone has also been associated with improved food efficiency in CKD. Indeed, Mehls et al.[58] reported that uremic rats receiving recombinant growth hormone gained more weight per gram food intake than uremic rats receiving vehicle. Combining growth hormone and insulin-like growth factor-1 improved food utilization and anabolic response in experimental[59] and clinical CKD.[60]

Muscle wasting is a predominant feature of CKD and is particularly present in long-term maintenance dialysis patients. Low muscle mass is associated with increased mortality.[61] Muscle wasting results partly from reduced physical activity (see section below) but also because of resistance to anabolic factors. The impaired action of growth hormone and/or insulin-like growth factor-1 has been studied in detail during maintenance dialysis in children and adults as well.[62–64] Short-term therapeutic interventions have been successful in improving body composition,[65,66] however side effects request long-term studies that are not yet available. As there is a testosterone deficit, which is associated with superimposed mortality in men,[67] it may be interesting to test short courses of androgen support in case of severe cachexia and muscle wasting,[68] in association with physical training. Indeed, most anabolic factors will not be efficient if they are not associated with a rehabilitation program.

In order to clarify the definition of kidney-associated protein–energy wasting, the International Society for Renal Nutrition and Metabolism released in 2008 a nomenclature paper focused on the causes, consequences, and diagnostic criteria of impaired nutritional status in CKD patients.[24] Four groups of parameters were examined (Table 1): serum chemistry, body composition, muscle mass, and dietary intake. For each parameter, a threshold was given based on the most recent epidemiological studies in CKD patients. Protein–energy wasting is then identified if at least one parameter is found below recommendation in three of the four marker groups,[24] and this simple estimation can be performed at bedside. The next steps are to validate this classification and identify a protein–energy wasting score that can predict mortality. A preliminary approach has been recently reported by de Mutsert et al.[69] using the 7-point subjective global assessment scale, which is a combination of clinical symptoms of malnutrition and biological abnormalities. In this prospective cohort of 1601 maintenance hemodialysis patients followed in the NECOSAD-II study, the increase in 7 years mortality was clearly linked to a point-by-point decrease in subjective global assessment.[69]


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