Mechanisms activated by kidney disease and the loss of muscle mass

The daily turnover of cellular proteins is large, with amounts equivalent t o the protein contained in 1.0 to 1.5 kg of muscle. Consequently, even a sm all, persistent increase in the rate of protein degradation or decrease in protein synthesis will result in substantial loss of muscle mass. Activatio n of protein degradation in the ubiquitin-proteasome system is the mechanis m contributing to loss of muscle mass in kidney disease. Because other cata bolic conditions also stimulate this system to cause loss of muscle mass, t he identification of activating signals is of interest. A complication of k idney disease, metabolic acidosis, activates this system in muscle by a pro cess that requires glucocorticoids. The influence of inflammatory cytokines on this system in muscle is more complicated, as evidence indicates that c ytokines suppress the system, but glucocorticoids block the effect of cytok ines to slow protein breakdown in the system. New information identifying m echanisms that activate protein breakdown and the rebuilding of muscle fibe rs would lead to therapies that successfully prevent the loss of muscle mas s in kidney disease and other catabolic illnesses. (C) 2001 by the National Kidney Foundation, Inc.