Diffuse glomerulosclerosis without tubular injury does not directly manifest renal dysfunction in nephrotic mice (ICGN strain).

Chronic renal disease is characterized by pathological conditions, caused by a progressive and irreversible loss of renal function. The nephrotic mouse (ICGN strain) is a useful model for demonstrating progressive nephrotic syndrome (NS). In the present study, we examined the natural course of kidney disease shown by the NS mice, aging 6-26 weeks, in order to characterize their pathological conditions. Urine and serum biochemistry revealed that massive albuminuria and hypoalbuminemia were evident in the NS mice throughout the observation period and that blood urea nitrogen (BUN) and serum creatinine levels began to increase from 14 weeks after birth. Renal histopathology demonstrated that glomerulosclerotic lesion was diffusely observed in the renal cortical area from 6 weeks after birth. Furthermore, the tubular lesions, characterized by tubular cellular atrophy and luminal cast formation, became mild to moderate and severe in the 14- and 26-week-old NS mice, respectively. Although the 6- and 10-week-old NS mice exhibited diffuse mesangial expansion, BUN and serum creatinine levels were normal as long as the tubular architecture remained almost intact. There was a good correlation between BUN level and tubular injury index (r2 = 0.860, p < 0.001), while no significant relationship was seen between the BUN level and glomerular matrix index. Our model, an experimental analogue of human chronic renal disease, clearly demonstrates that glomerulosclerosis is not always a direct determinant for renal dysfunction.