EVIDENCE OF OXIDANT INJURY AND TUBULAR DAMAGE IN EARLY DIABETIC NEPHROPATHY

Two groups of patients with insulin-dependent diabetes mellitus of >10 years duration and either persistent normoalbuminuria (group 1, n=49; albumin excretion <30 mg/day) or microalbuminuria (group 2, n=33; alb umin excretion 30-300 mg/day) were investigated for evidence of free o xygen radical activity (erythrocytic superoxide dismutase and glutathi one peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (reti nol-binding protein) and tubular enzymuria (N-acetyl-glucosaminidase a nd leucine aminopeptidase) were also measured. Healthy controls (n=38) were matched for age and sex, Groups 1 and 2 were similar in terms of age, sex, duration of diabetes and recent glycaemic control. Serum ch olesterol and creatinine were similar in all three groups. Free-radica l activity and oxidant injury were significantly higher in groups 1 an d 2 than in controls (p<0.001). Glomerular proteinuria, tubular protei nuria and enzymuria were significantly higher in group 2 than in group 1 and controls (p<0.01). Group 1 had significantly higher transferrin uria, tubular enzymuria and tubular proteinuria than controls. However , groups 1 and 2 were similar in degree of free oxygen radical generat ion and oxidant injury. In diabetic nephropathy, oxidant injury and re nal tubular damage accompany and may even precede microalbuminuria. Th e presence of these abnormalities in the absence of glomerular protein uria favours the hypothesis that alterations first occur in the peritu bular microcirculation, which by causing oxidant injury and tubular da mage, may initiate diabetic nephropathy.