Circulating advanced glycation end product levels in rats rapidly increase with acute renal failure

Circulating advanced glycation end product levels in rats rapidly increase with acute renal failure.BackgroundAdvanced glycation end products (AGEs) are formed on proteins and peptides slowly during aging, and they accumulate in circulation and tissues in diabetes and chronic renal failure. Except for nonenzymatic glycation, enhanced oxidative/carbonyl stress is supposed to participate in their formation. The Kidney plays a key role in disposal of AGEs, particularly AGE-peptides. We assumed that even a short time combination of enhanced oxidative/carbonyl stress and a lack of renal function should result in elevation of circulating AGE levels.MethodTo verify this hypothesis, two models of acute renal failure in rats, bilateral nephrectomy and bilateral ureteral ligation, were employed, and the data were compared with those of sham-operated animals.ResultsAGE levels determined fluorimetrically or as carboxymethyllysine concentration rose by a factor of three within 48 hours. Enhanced levels of malondialdehyde and lipofuscin pointed to an enhanced oxidative/carbonyl stress. Activity of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase were not compromised, or were even elevated, respectively. Total antioxidant status increased, probably as a consequence of an accumulation of indols and benzoic acid derivatives, uremic toxins with scavenging capacities, as shown for hippurate.ConclusionsEvidence was given that circulating AGEs in the model of acute renal failure in rats undergo a substantial rise within a short time period. A source of increased AGEs is not clear, since except for the lack of the kidney function, accelerated synthesis of AGEs under enhanced oxidative/carbonyl stress as well as liberation of AGEs from tissues due to protein catabolism might be anticipated. If AGEs accumulate in acute renal failure in humans, their contributiion to acute toxicity, or of the development of the complications later, might be of importance