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.