Oxidized LDL-anti-oxidized LDL immune complexes and diabetic nephropathy

Abstract

Aims/hypothesis: Oxidized LDL is immunogenic and immune complexes formed by oxidized LDL and corresponding antibodies are pro-atherogenic and pro-inflammatory. Considering that macroalbuminuria is a risk factor for coronary heart disease and that common pathogenic factors for atherosclerosis and glomerulosclerosis exist, our aim was to determine whether the amount and/or characteristics of oxidized LDL- anti-oxidized LDL complexes correlated with the degree of albuminuria in patients with Type I (insulin-dependent) diabetes mellitus.

Methods: We studied 33 macroalbuminuric patients (albumin excretion rate >300 mg/24 h) and 29 microalbuminuric patients (albumin excretion rate >or=30 mg/24 h and <or=300 mg/24 h) who were matched for age, sex and HbA(1C) concentrations with 43 patients with normal albuminuria. In all patients we isolated and characterized oxidized LDL-anti-oxidized LDL complexes. A subgroup of 47 patients (22 with normal albuminuria, 11 with microalbuminuria, and 14 with macroalbuminuria) was randomly selected from the larger group for characterization of the antibody moiety of oxidized LDL immune complexes.

Results: The concentrations of oxidized LDL immune complexes were increased in patients with macroalbuminuria (total cholesterol in immune complexes isolated from patients with macroalbuminuria was 272+/-20 vs 204+/-18 micro g/ml in patients with normoalbuminuria, p<0.03). Also, the Kd of oxLDL antibodies isolated from the immune complexes was lower in patients with abnormal albuminuria than in patients with normoalbuminuria (0.86+/-0.1x10(-8) vs 1.13+/-0.1x10(-8) mol/l, p<0.05).

Conclusion/interpretation: The data indicate that high concentrations of oxidized LDL-anti-oxidized LDL complexes, particularly when formed with antibodies of higher avidity, are associated with abnormal proteinuria.