Morphological studies on focal glomerular sclerosis (FGS) in rat: Disturbance of glomerular polyanion

We carried out an experiment in order to elucidate the pathogenesis of focal glomerular sclerosis (FGS) showing the steriod-resistant nephrotic syndrome . In the examinations we observed histopathological findings centering around the loss of glomerular anionic sites caused by some factors. The experiment was conducted in Sprague-Dawley male rats divided into 4 groups of 1) the unilateral nephrectomy+2.5% glycine overload diet group (NG), 2) the unilateral nephrectomy+commercial diet group (NC), 3) the 2.5% glycine overload diet group (G), 4) commercial diet only group (C). The FGS characterized with focal segmental and/or hyalinosis (FSH) of the glomeruli were observed since 3 months later in the NG and NC groups and since 11 months later in the G and C groups. The FSH were dominantly distributed in the juxtamedullary cortex rather than the subcapsular cortex in a rate of 5 to 1. The NG and NC groups showed high proteinuria, whereas the G and C groups indicated within normal extents. In colloidal iron stain the decrease and/or lack in colloidal iron staining was observed since 3 months later in the NG and NC groups, since 5 months later in the G group, and since 7 months later in the C group. And in each groups there was shown the relationship between the degree of glomerular anionic loss and the urinary protein excretion. The lack of colloidal iron affinity in the non-sclerotic glomeruli is frequently observed from a period before onset of FSH and accordingly this may be a precursor of sclerotic lesion. The hemodynamic overload due to unilateral nephrectomy, anatomical differences in vessels and toxicity of glycine cause disturbances at glomerular anionic sites, as a result protein excretion and expansion of the mesangial matrix are induced, and these seem to become the causes for incidence of segmental sclerosis and vulnerability of the glomeruli.