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Advanced glycation end products: a Nephrologist's perspective
D S Raj1, D Choudhury, T C Welbourne
1Department of Medicine, Lousiana State University Medical Center, Shreveport, LA,USA.
Summary
Advanced glycation end products (AGEs) contribute to aging and diabetes complications. Novel agents like aminoguanidine show promise in preventing AGE-related diseases.
Area of Science:
- Biochemistry
- Gerontology
- Nephrology
Background:
- Advanced glycation end products (AGEs) are linked to aging, diabetes, and renal failure.
- AGEs are formed from sugar condensation with proteins and act as uremic toxins.
- They contribute to vascular and renal complications, and age-related diseases like Alzheimer's.
Purpose of the Study:
- To explore the role of AGEs in the pathogenesis of aging and diabetes complications.
- To investigate the accumulation of AGEs in renal failure and their role in dialysis-related amyloidosis.
- To evaluate potential therapeutic strategies for AGE-related conditions.
Main Methods:
- Review of in vivo and in vitro studies on AGEs.
- Analysis of AGE accumulation in aging, diabetes, and renal failure.
- Examination of therapeutic agents targeting AGE formation and cross-linking.
Main Results:
- AGEs accelerate atherosclerosis and are implicated in diabetic nephropathy progression.
- AGEs accumulate in renal failure due to reduced excretion and increased generation.
- Dialysis cannot normalize AGE levels; islet-cell transplantation can normalize glycosylation.
Conclusions:
- AGEs play a critical role in the pathogenesis of diabetes, uremia, and aging complications.
- Aminoguanidine (AGN) reduces AGE formation and inhibits their action, improving neuropathy and delaying retinopathy/nephropathy.
- N-Phenacylthiazolium bromide cleaves AGE cross-links, offering potential therapeutic avenues for AGE-related diseases.