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ABSTRACT. Progressive glomerular injury associated with early-onset proteinuria was investigated in male Osborne-Mendel (OM) rats aged 5 to 20 weeks. Age-matched male Fischer 344 (F344) rats were used for comparison. OM rats developed mild hypertension and selective proteinuria (albuminuria) from 5 weeks of age, and non-selective proteinuria from 7 weeks of age. Light microscopy of OM kidney revealed hyaline droplets in the podocyte at 5 weeks of age and vacuolation of podocytes and adhesion of the capillary loop to the Bowman's capsule at 7 weeks of age. Segmental glomerulosclerosis developed in OM rats from 15 weeks of age, and global sclerosis appeared at 20 weeks of age. Desmin, a marker of podocye injury, was expressed in podocytes from 10 weeks of age, and the intensity of expression increased with age. Ultrastructurally, damage to podocytes such as effacement of foot processes, decreasing number of filtration slits, and rearrangement of the actin cytoskeleton were observed from 5 weeks of age in OM rat. Glomerular volume in OM rats increased with age and was consistently higher than in age-matched F344 rats. The number of WT-1-positive podocytes and vimentin-positive podocyte area were lower in OM rats and decreased with age. These findings suggest that glomerulonephropathy in male OM rats is associated with glomerular hypertrophy, progressive podocytopathy, and a reduction in podocyte number and area. Renal injury in OM rats was associated with development of early-onset proteinuria and was more progressive than in age-matched F344 rats. Osborne-Mendel (OM) rats have long been used as obesity-prone rats [22]. When fed a high fat diet, they are susceptible to the development of obesity and demonstrate several metabolic abnormalities, including cardiac and renal hypertrophy, hyperglycemia, and hyperinsulinemia [4,14]. These clinical symptoms are also characteristic of human metabolic syndrome, suggesting that OM rats could provide an animal model for human metabolic syndrome. Metabolic syndrome is a reported risk factor for progression of chronic kidney disease and for end-stage renal disease (ESRD) [23]. This time, characteristic progressive glomerular injury associated with early onset proteinuria in OM rats was found in our laboratory. However, to our knowledge, there have been no detailed pathological studies on renal disease, especially on glomerular injury in OM rats.Podocytes are highly differentiated and specialized epithelial cells that line the outer aspect of the glomerular basement membrane (GBM). In the normal glomerulus, they serve as the final barrier against urinary protein loss. Foot processes of neighboring podocytes interdigitate over the capillary walls and are bridged by the slit diaphragms, thus forming the final filtration barrier. In proteinuric nephropathy, injuries to podocytes may develop in the early stage of the disease, and the ensuing reduction in podocyte number occurs continuously [20]. Detachment of podocytes from the GBM results in a decrease in the number of glomerular p...

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