Advanced Glycation End-product - Clearance

Clearance

Cellular proteolysis of AGEs produces AGE peptides and "AGE free adducts" (AGE adducts bound to single amino acids), which, after being released into the plasma, can be excreted in the urine. The resistance of extracellular matrix proteins to proteolysis renders AGEs of these proteins less conducive to elimination. While the AGE free adducts are released directly into the urine, AGE-peptides have been shown to be endocytosed by the epithelial cells of the proximal tubule and subsequently degraded by the endolysosomal system to produce AGE-amino acids. It is hypothesized that the AGE-amino acids are then exported back into the lumen of the nephron for subsequent excretion. AGE free adducts are the major form through which AGEs are excreted in urine, with AGE-peptides occurring to a lesser extent, but accumulate in the plasma of patients with chronic renal failure.

Larger, extracellularly-derived AGE proteins cannot pass through the basement membrane of the renal corpuscle and must first be degraded into AGE-peptides and AGE free adducts. Peripheral macrophage as well as liver sinusoidal endothelial cells and Kupffer cells have been implicated in this process, although the real-life involvement of the liver has been disputed.