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Glycation End Products: A Nephrologist's Perspective
Raj, D. S. C., Choudhury, D., Welbourne, T. C., Levi, M.
Abstract
broadcast on www.provet.co.uk
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Abstract
Advanced glycation end products (AGEs) are a heterogeneous group of molecules
that accumulate in plasma and tissues with advancing age, diabetes, and renal
failure. There is emerging evidence that AGEs are potential uremic toxins and
may have a role in the pathogenesis of vascular and renal complications
associated with diabetes and aging. AGEs are formed when a carbonyl of a
reducing sugar condenses with a reactive amino group in target protein. These
toxic molecules interact with specific receptors and elicit pleiotropic
responses. AGEs accelerate atherosclerosis through cross-linking of proteins,
modification of matrix components, platelet aggregation, defective vascular
relaxation, and abnormal lipoprotein metabolism. In vivo and in vitro studies
indicate that AGEs have a vital role in the pathogenesis of diabetic
nephropathy and the progression of renal failure. The complications of normal
aging, such as loss of renal function, Alzheimer's disease, skin changes, and
cataracts, may also be mediated by progressive glycation of long-lived
proteins. AGEs accumulate in renal failure as a result of decreased excretion
and increased generation resulting from oxidative and carbonyl stress of
uremia. AGE-modified beta(2)-microglobulin is the principal pathogenic
component of dialysis-related amyloidosis in patients undergoing dialysis.
Available dialytic modalities are not capable of normalizing AGE levels in
patients with end-stage renal disease. A number of reports indicated that
restoration of euglycemia with islet-cell transplantation normalized and
prevented further glycosylation of proteins. Aminoguanidine (AGN), a
nucleophilic compound, not only decreases the formation of AGEs but also
inhibits their action. A number of studies have shown that treatment with AGN
improves neuropathy and delays the onset of retinopathy and nephropathy. N-Phenacylthiazolium
bromide is a prototype AGE cross-link breaker that reacts with and can cleave
covalent AGE-derived protein cross-links. Thus, there is an exciting
possibility that the complications of diabetes, uremia, and aging may be
prevented with these novel agents.
Reference
AMERICAN JOURNAL OF KIDNEY DISEASES , 35(3):365-380
2000
Updated January 2016
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