K. Sebekova et al., Circulating advanced glycation end product levels in rats rapidly increasewith acute renal failure, KIDNEY INT, 59, 2001, pp. S58-S62
Background. Advanced glycation end products (AGEs) are formed on proteins a
nd peptides slowly during aging, and they accumulate in circulation and tis
sues in diabetes and chronic renal failure. Except for nonenzymatic glycati
on, enhanced oxidative/carbonyl stress is supposed to participate in their
formation. The kidney plays a key role in disposal of AGEs, particularly AG
E-peptides. We assumed that even a short time combination of enhanced oxida
tive/carbonyl stress and a lack of renal function should result in elevatio
n of circulating AGE levels.
Method. To verify this hypothesis, two models of acute renal failure in rat
s, bilateral nephrectomy and bilateral ureteral ligation, were employed, an
d the data were compared with those of sham-operated animals.
Results. AGE levels determined fluorimetrically or as carboxymethyllysine c
oncentration rose by a factor of three within 48 hours. Enhanced levels of
malondialdehyde and lipofuscin pointed to an enhanced oxidative/carbonyl st
ress. Activity of antioxidant enzymes such as superoxide dismutase and glut
athione peroxidase were not compromised, or were even elevated, respectivel
y. Total antioxidant status increased, probably as a consequence of an accu
mulation of indols and benzoic acid derivatives, uremic toxins with scaveng
ing capacities, as shown for hippurate.
Conclusions. Evidence was given that circulating AGEs in the model of acute
renal failure in rats undergo a substantial rise within a short time perio
d. A source of increased AGEs is not clear, since except for the lack of th
e kidney function, accelerated synthesis of AGEs under enhanced oxidative/c
arbonyl stress as well as liberation of AGEs from tissues due to protein ca
tabolism might be anticipated. If AGEs accumulate in acute renal failure in
humans, their contribution to acute toxicity, or of the development of the
complications later, might be of importance.