Figure 3.

Possible mechanisms for pGSN depletion and its consequences in chronic renal failure. Chronic renal failure inhibits pGSN synthesis and accelerates clearance. Muscle is the major source of pGSN biosynthesis, and the reduction of muscle mass associated with chronic renal failure predictably would reduce net pGSN production. The failure to eliminate toxins in renal failure causes widespread tissue destruction (especially endothelial), leading to exposure of cytoplasmic actin into the plasma and pGSN sequestration in broken cells. In addition, release of inside-out membrane vesicles with attached actin filaments from damaged cells would result in detectable circulating actin, and circulating actin accelerates pGSN clearance. Low pGSN results in impaired buffering of inflammatory mediators such as platelet-activating factor, promoting vascular complications and rendering patients susceptible to the lethal effects of sepsis.