ABSTRACT
Sarcopenia, frailty, protein-energy wasting (PEW), and cachexia are common in patients with chronic kidney disease (CKD) and are associated with an increased death risk from cardiovascular diseases and infection. However, while even minor renal dysfunction is an independent predictor of adverse cardiovascular prognosis, wasting becomes clinically manifest at an advanced stage, early before or during the dialytic stage. Mechanisms causing loss of muscle protein and fat are complex and not always associated with anorexia but are linked to several abnormalities that stimulate protein degradation and/or decrease protein synthesis. Moreover, data from experimental CKD indicate that uremia specifically blunts the regenerative potential in skeletal muscle, by acting on muscle stem cells. In this discussion, recent findings regarding the mechanisms responsible for wasting and cachexia in CKD patients are discussed. During the course of CKD, the loss of kidney excretory and metabolic functions proceeds together with the activation of pathways of endothelial damage, inflammation, acidosis, alterations in insulin signaling, and anorexia, which are likely to orchestrate net protein catabolism and the wasting syndrome. Of note, inflammation and other CKD-associated catabolic pathways lead also to accelerated aging and frailty to induce a senescent phenotype, which associates with premature vascular disease, osteoporosis, depression, and cognitive impairment.
