The meaning of serum levels of advanced glycosylation end products in diabetic nephropathy

It has been reported that advanced glycosylation end products (AGEs) play a n important role in the development of diabetic complications. To evaluate the relationship between serum AGEs and diabetic nephropathy, we measured s erum AGE levels in diabetic patients with normoalbuminuria (N), microalbumi nuria (M), overt proteinuria (O), and hemodialysis (HD), non diabetic patie nts with nephropathy, and age-matched control subjects using the enzyme-lin ked immunosorbent assay (ELISA). Urine AGE levels were also measured in the se subjects except group HD. Serum AGE levels in diabetic patients were not significantly higher than those in the normal subjects. When we compared s erum AGE levels among various stages of diabetic nephropathy, groups O and HD had significantly higher serum AGE levels than the other groups. Serum A GE levels in group HD were almost 6-fold higher than those in groups N and M. In contrast, there were no significant differences in urinary AGE levels among any diabetic groups. As for the variables that determine serum AGE l evels in diabetic patients, there was no significant Correlation between se rum AGEs and fasting blood glucose, hemoglobin A(1c) (HbA(1c)), or duration of diabetes. In contrast, serum:AGEs showed a strong correlation with seru m creatinine and an inverse correlation with creatinine clearance. To evalu ate the relationship between serum AGEs and oxidative stress in diabetic ne phropathy, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum malondial dehyde (MDA), which are biological markers of total oxidative stress in viv o, were also examined. Both urinary 8-OHdG and serum MDA levels were signif icantly higher in diabetic patients with proteinuria versus those without p roteinuria. However, there was no significant correlation between serum AGE s and urinary 8-OHdG or serum MDA levels in diabetic patients. These result s suggest that the accumulation of serum AGEs in diabetic nephropathy may b e mainly due to decreased removal in the kidney rather than increased produ ction by high glucose levels or oxidative stress. Copyright (C) 2000 by W.B . Saunders Company.