Advanced glycation end-products in diabetic nephropathy

Advanced glycation end-products (AGEs) are the pigmented and fluorescent adduct formed by a non-enzymatic reaction between sugar and protein. Since AGEs are generated in high glucose milieu, then induce the structural and functional alteration of matnx proteins, and have biological effects on various kinds of cells including mesangial cells, AGEs have been implicated in tissue damage of diabetic nephrophathy. To elucidate the factor(s) that determine the AGEs level in diabetic nephrophathy, we quantitated the plasma pentosidine level of different status of diabetic nephrophathy by HPLC assay. The plasma pentosidine level in diabetic nephrophathy was found to be determined by factors such as renal function, control of glucose and the patient's age; of these, renal function was the most critical factor. For a better understanding of the pathological role of AGEs in diabetic nephrophathy, we then examined renal tissues of diabetic nephrophathy immunohistochemically using antibodies specific for AGE proteins. Immunohistochemistry revealed the positive immunostaining for AGEs in the expanded mesangial area of diffuse diabetic glomerulosclerosis. The degree of staining was stronger than that in patients of IgA nephropathy with a similar degree of mesangial expansion. The nodular lesions, characteristic of diabetic nephrophathy, were also stained positive for AGEs. These findings suggests a potential link of AGEs accumulation, which may be determined by renal function, control of glucose and age, to renal tissue damage in diabetic nephrophathy.