EXPERIMENTAL FOCAL SEGMENTAL GLOMERULOSCLEROSIS IN MICE

Although a lot of animal models of proteinuria have been established, proposals for the mechanisms of proteinuria are still controversial. I n this work, during an 18-day trial, mice injected with a single dose of adriamycin (AD) rapidly showed combined glomerular albuminuria and immunoglobulinuria, progressively elevated levels of nitrite/nitrate i n urine, hypercholesterolemia, abnormal renal function, segmentally or globally glomerular hyalinosis/sclerosis associated with tubular atro phy, enhanced glomerular deposition of immunoglobulins and fibrinogen, augmented expression of matrix components in the whole glomerular tuf t, and loss of glomerular negative charge property. These laboratory a nd pathological features are comparatively similar to those of human f ocal segmental glomerulosclerosis in the advanced state, Juxtamedullar y glomeruli appear to be more susceptible to the AD-related nephrotoxi city than those in the superficial renal cortex. A change in size-depe ndent glomerular permselectivity may precede a charge-dependent defect in glomeruli in this mouse model of proteinuria. Data in this study c onfirm the hypothesis of glomerular hyperfiltration involved in the pa thogenesis of this chronic glomerulopathy associated with proteinuria in mice, In addition, nitric oxide may play a crucial role in the prog ression of the chronic glomerulopathy model.