Document Detail

Mechanisms for the formation of glycoxidation products in end-stage renal disease.
MedLine Citation:
PMID:  10844627     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Advanced glycation end products (AGEs) accumulate on tissue and plasma proteins in patients with renal failure far in excess of normal aging or diabetes. The aim of these studies was to elucidate the nature of the precursors and the pathways that lead to an accelerated formation of two structurally identified AGEs [pentosidine and Nepsilon(carboxymethyl)lysine (CML)] in the uremic milieu. METHODS: Serum levels of the glycoxidation products, pentosidine and CML, were quantitated by high-performance liquid chromatography in uremic patients treated by dialysis. The formation of early glycation products (as furosine) and late glycoxidation products was modeled in uremic serum and in spent peritoneal dialysate. RESULTS: Clinical factors that affect circulating levels of AGEs included dialysis clearance and dialyzer membrane pore size, but not the presence or absence of diabetes. Both pentosidine and CML form at an accelerated rate in serum from uremic patients. Chelating agents most effectively slow the formation in vitro. In uremic fluids, the primary mechanism of formation of pentosidine is through the Amadori pathway. The primary mechanism of formation of CML is through metal-chelated autoxidation of reducing sugars generating reactive carbonyl precursors. In uremic serum, the presence of an unidentified reactive low molecular weight precursor accelerates the formation of pentosidine. CONCLUSIONS: The formation of the two glycoxidation products, pentosidine and CML, proceeds by different pathways and is enhanced by different precursors in the uremic milieu. The formation of both AGEs is markedly enhanced by metal-catalyzed reactions, evidence for the presence of increased metal-ion mediated oxidant stress in uremia.
M F Weiss; P Erhard; F A Kader-Attia; Y C Wu; P B Deoreo; A Araki; M A Glomb; V M Monnier
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Kidney international     Volume:  57     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-08-24     Completed Date:  2000-08-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2571-85     Citation Subset:  IM    
Division of Nephrology, Department of Medicine, University Hospitals of Cleveland, Cleveland, Ohio 44106, USA.
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MeSH Terms
Aged, 80 and over
Arginine / analogs & derivatives,  blood
Enzyme Inhibitors / pharmacology
Glucose / metabolism
Glycosylation End Products, Advanced / biosynthesis*,  blood
Guanidines / pharmacology
Kidney Failure, Chronic / blood,  metabolism*,  therapy
Lysine / analogs & derivatives,  blood
Maillard Reaction
Middle Aged
Peritoneal Dialysis
Renal Dialysis
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Glycosylation End Products, Advanced; 0/Guanidines; 124505-87-9/pentosidine; 21291-40-7/fructosyl-lysine; 50-99-7/Glucose; 56-87-1/Lysine; 5746-04-3/N(6)-carboxymethyllysine; 74-79-3/Arginine; 79-17-4/pimagedine

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