Glycoxidation-modified macrophages and lipid peroxidation products are associated with the progression of human diabetic nephropathy

The aim of this study is to Investigate the role of glomerular macrophages activated by glycoxidation and lipid peroxidation products in the progressi on of glomerular lesions In diabetic nephropathy. Renal biopsy samples from 43 patients with diabetes (age, 54 +/- 14 years) and 10 control cases were immunohistochemically examined for the expression of carboxymethyllysine ( CML), a representative glycoxidative product; oxidized phosphatidylcholine (OX-PC), a representative lipid peroxidation product; leukocyte common anti gen (LCA); CD68; and macrophage scavenger receptor (MSR) class A. The sever ity of the diffuse lesions in each glomerulus was histologically graded fro m 0 to IV. When grade II and III lesions had Kimmelstiel-Wilson (KW) nodule s, they were placed in a new category called grade III with KW nodules. The number of cells positive for CML, Ox-PC, LCA, CD68, and MSR was compared i n different grades. The number of macrophages per glomerulus increased with the glomerular lesion grade and was highest in grade III with KW nodules. Conversely, the number of lymphocytes did not parallel the grade of glomeru lar lesions. Almost 50% of macrophages contained CML, and more than 40% of those were observed in exudative lesions, tuft. adhesions, and at the perip hery of KW nodules. Ox-PC accumulated in 50% of CML-positive macrophages, w hich coexpress MSR. Macrophages positive for CML and Ox-PC increased with t he grade. Glomerular macrophages may be activated by glycoxidative and lipi d peroxidation products through MSR and may have a role In the development of human diabetic glomerulosclerosis. (C) 2001 by the National Kidney Found ation, Inc.