ACCUMULATION OF ALBUMIN-LINKED AND FREE-FORM PENTOSIDINE IN THE CIRCULATION OF UREMIC PATIENTS WITH END-STAGE RENAL-FAILURE - RENAL IMPLICATIONS IN THE PATHOPHYSIOLOGY OF PENTOSIDINE

Pentosidine is an advanced glycation end product and its formation is shown to be closely related to oxidative processes. Recent studies hav e shown that pentosidine levels are increased not only in plasma and m atrix proteins from diabetic patients, but also markedly in nondiabeti c hemodialysis patients. Currently, the mechanism of accumulation and kinetics of pentosidine formation in hemodialysis patients remain unkn own. Gel filtration of uremic plasma revealed that plasma pentosidine exists in the albumin fraction (approximately 90%) and, interestingly, in free form (approximately 5%) as well. Plasma free pentosidine was undetectable in subjects with normal renal function. There was a signi ficant correlation between the plasma levels of albumin-linked and fre e pentosidine in hemodialysis patients. Kinetic studies indicated that dietary pentosidine was absorbed into the circulation and that, after either oral or intravenous administration of pentosidine to intact or nephrectomized rats, the plasma free pentosidine level was closely li nked to the level of renal function. These findings demonstrate that: (I) Pentosidine accumulates as albumin-linked and in free form in the circulation of uremic patients; (2) dietary pentosidine be absorbed in to the circulation, thus being one possible origin of circulating free pentosidine; (3) free pentosidine may accumulate as a result of decre ased glomerular filtration; and (4) the mechanism of accumulation of a lbumin-linked pentosidine is not related to high glucose levels. It su ggests the simultaneous accumulation, during renal failure, of either unknown pentosidine precursor(s) or catalyst(s) of glycoxidation, inde pendent of glucose.