Chronic uremia is often characterized by wasting of muscle and fat mass, which
has been defined as protein-energy wasting (PEW), and is responsible for
substantial worsening of patient outcome in terms of morbidity and mortality,
mostly from cardiovascular events. Despite major advances in patient treatment,
nutritional outcome in patients with end-stage renal disease has not improved
substantially in recent years. Extensive research in this field has provided
plausible explanations for this limitation by indicating that the pathogenesis of
PEW in kidney disease is complex and multifactorial. Complexity involves
underlying metabolic alterations, including inflammation, oxidative stress, and
insulin resistance. In addition, patient heterogeneity is increasing with large
numbers of obese individuals as a result of the ongoing obesity epidemics.
Several tissues are involved in cross-talk and contribute to metabolic
derangements, including adipose tissue, the gut, and the central nervous system,
with novel mediators including the gastric hormone ghrelin. Acknowledging its
complex pathogenesis may favor the development of novel and more effective
therapeutic tools for PEW. These should ideally be effective in treating the
underlying common mechanisms of wasting, which appear to include oxidative
stress, inflammation, and insulin resistance.
