SPECIFIC FLUORESCENCE ASSAY FOR ADVANCED GLYCATION END-PRODUCTS IN BLOOD AND URINE OF DIABETIC-PATIENTS

Late rearrangement products that accumulate by glycation of proteins, known as advanced glycation end products (AGEs), have been implicated in the pathogenesis of complications related to diabetes. Circulating AGEs, especially in the form of a small peptide (AGE-peptide) of less than 10 kd, increase in the blood of diabetic patients with end-stage renal disease (ESRD). The aim of the study was to evaluate AGE-peptide levels by measuring AGE-specific fluorescence (excitation at 370 nm a nd emission at 440 nm) and to examine the relationship between AGE-pep tide and diabetic nephropathy. AGE-specific fluorescence in serum and urine were examined in diabetic subjects with various levels of renal complications of varying severity: normoalbuminuria (N), microalbuminu ria (Mi), macroalbuminuria (Ma), chronic renal failure (C), and hemodi alysis (HD). We also assessed correlations among the AGE-peptide level and age, duration of diabetes, hemoglobin A(1c) (HbA(1c)), serum crea tinine, and creatinine clearance. Serum and urine AGE-peptide levels i n C and HD were significantly higher than in N, Mi, and Ma. Serum AGE- peptide levels were significantly correlated with serum creatinine (r = .866, P < .0001) and creatinine clearance (r = -.720, P < .0001) but not with duration of diabetes or age. There was a significant correla tion between AGE-peptide levels measured by enzyme-linked immunosorben t assay (ELISA) and levels determined from the specific fluorescence i ntensity (r = .688, P < .0001). These findings suggest that renal func tion may play a greater role in the accumulation of AGEs than persiste nt hyperglycemia in diabetic patients. Measurement of AGE-specific flu orescence (ie, AGE-peptide) may serve as a simple and useful test to a ssess circulating AGE levels and monitor AGE excretion. Copyright (C) 1998 by W.B. Saunders Company.