Immunogenicity of advanced glycation end products in diabetic patients and in nephropathic non-diabetic patients on hemodialysis or after renal transplantation

Advanced glycation end products (AGE) increase as a consequence of diabetic hyperglycemia and, in nephropathic patients, following renal function loss. Protein-bound AGE behave as immunogens, inducing formation of specific antibodies (Ab-AGE). In this work AGE immunogenicity was studied in 42 diabetic patients, 26 nephropathic patients on hemodialysis and 26 patients with end-stage renal disease who underwent kidney transplantation and in 20 normal subjects. Non-oxidation-derived AGE (nox-AGE), oxidation-derived AGE (ox-AGE) and Ab-AGE were measured by competitive or direct enzyme-linked immunosorbent assay (ELISA) and circulating immune complexes (CIC) by C1q ELISA. Nox-AGE increased significantly in all patient groups (p≤0.05 to ≤0.0001) except in patients on hemodialysis for less than 6 yr. Ox-AGE were only significantly increased in patients transplanted more than 3 yr previously (p<0.05). Ab-AGE were significantly lower than controls in both diabetic groups and in patients on hemodialysis for more than 6 yr (p<0.005 to <0.0001) and not unlike controls in the other groups. These results demonstrate that hemodialysis or renal tranplantation can, initially, reduce either nox- or ox-AGE levels, which however go back to being high in time. Renal transplantation fails to normalize nox-AGE. More importantly, plasma Ab-AGE levels are reduced or unchanged in all patient groups in comparison with controls, despite higher circulating AGE levels. This suggests the importance of tissue-bound AGE as Ab-AGE targets. Additional interventions are needed to control AGE levels in treated nephropathic patients. The search and quantification of specific Ab-AGE would give more meaningful results if performed over specific tissue specimens.