Cellular and extracellular proteins suffer significant damage in vivo by glycation. Physiological proteolysis of proteins damaged by glycation forms glycation free adducts that are released into plasma for urinary excretion. Inefficient elimination of these free adducts in uremia leads to their accumulation. In mild renal insufficiency, plasma glycation free adducts accumulated as renal clearance declined. In patients with end-stage renal disease, plasma glycation free adducts were increased up to 18-fold on peritoneal dialysis and up to 40-fold on hemodialysis. Glycation free adduct concentrations in peritoneal dialysate increased with dialysate dwell time, achieving concentrations in the dialysate higher than in plasma--suggesting that glycation adduct formation may occur in the peritoneal cavity and active transport into the peritoneal cavity may occur. In hemodialysis, plasma glycation free adducts equilibrated rapidly across the dialysis membrane, with both plasma and dialysate concentrations decreasing during a dialysis session. Therefore, protein glycation free adducts normally excreted efficiently in urine show profound mishandling and accumulation in chronic renal failure. Their accumulation may impair vascular cell function and contribute to morbidity and mortality in renal disease.