Age-associated changes in renal glomeruli of mice

To investigate age-associated changes in renal glomeruli of C57BL/6 female mice, we used a single radial immunodiffusion method to measure albumin excretion. Up to 100 mg/dl in urine samples was regarded as microalbuminuria. The mean amount of urinary albumin increased from 14.0 mg/dl at 6 months to 151.1 mg/dl at 24 months of age. Microalbuminuria occurred in 64.6% of tested mice by the time they were 24 months old, and 10% of the mice had marked albuminuria (more than 100 mg/dl) at that time. Parallel morphological study showed that renal mesangial changes were also age-dependent. Mesangial cell proliferation and spike lesions in glomerular capillary walls appeared in aged mice with microalbuminuria, and were then followed by diffuse glomerular sclerosis accompanied by marked albuminuria. Histological scores on damage in the renal mesangium with changes of glomerular basement membrane increased significantly with age from a mean score of 0 at 6 months to 3.24 at 24 months of age. Immunofluorescent study showed a marked deposition of IgG and IgM, but no complement component C3 in enlarged mesangium. Electron microscopic examination of diffuse sclerotic glomeruli in aged mice revealed amyloid substances. These results suggest that assays of albuminuria could be a useful method for early detection of age-associated renal deterioration.