Tissue and cell surface proteins modified nonenzymatically by glucose are shown to be highly active in protein cross-linking and have been implicated in tissue damage. The production of such protein-glucose interactions called advanced glycosylation endproducts (AGE) are recently shown to be processed by macrophages through a recently characterized high-affinity receptor. Coupling of AGE proteins to their AGE receptor results in TNF and IL-1 synthesis and secretion. This suggests that AGE may act as a signal for growth-promoting factor secretion in a coordinated replacement process during tissue remodeling. A disturbance of this balance may lead to pathologic proliferative response such as in the vasculopathy of diabetes and aging. Since peritoneal surface proteins can be modified by AGE after exposure to high-glucose, a similar pathogenetic process may be involved in the peritoneal fibrosis associated with chronic peritoneal dialysis.