Mechanisms for the formation of glycoxidation products in end-stage renal disease

Kidney Int. 2000 Jun;57(6):2571-85. doi: 10.1046/j.1523-1755.2000.00117.x.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Enzyme Inhibitors / pharmacology
  • Female
  • Glucose / metabolism
  • Glycation End Products, Advanced / biosynthesis*
  • Glycation End Products, Advanced / blood
  • Guanidines / pharmacology
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / metabolism*
  • Kidney Failure, Chronic / therapy
  • Lysine / analogs & derivatives
  • Lysine / blood
  • Maillard Reaction
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Peritoneal Dialysis
  • Renal Dialysis


  • Enzyme Inhibitors
  • Glycation End Products, Advanced
  • Guanidines
  • fructosyl-lysine
  • N(6)-carboxymethyllysine
  • Arginine
  • pentosidine
  • Glucose
  • Lysine
  • pimagedine