Natural history of renal lesions in spontaneously hypercholesterolemic (SHC) male rats

Spontaneously hypercholesterolemic (SHC) rats become hypercholesterolemic on normal diets. SHC rats, especially males, exhibit renal lesions similar to those found in focal segmental hyalinosis/sclerosis (FGS). We presented here a detailed natural history of serum lipid, renal function and pathological changes in male SHC rats from 5 to 40 weeks of age. Increased urinary protein excretion and glomerular injury were apparent before the detection of lipid or immune deposits, indicating that the renal lesions were not caused by these deposits. Serum total cholesterol levels, already high at 5 weeks, abruptly increased in concurrence with increased urinary protein excretion, suggesting that the severe hyperlipidemia of this strain is modified by a nephrotic syndrome. By 30 weeks of age, glomerular sclerosis was evident in more than half of the glomeruli and tubular dilatation was prominent, with an abrupt increase of BUN, SCr, and urinary volume; these findings indicate a rapid progression to renal failure. Our results suggest that SHC rats would be a very useful model to investigate the process leading to glomerular sclerotic lesion and renal failure, as well as the effect of hyperlipidemia on glomerular injury.