Genetic differences in susceptibility to glomerular sclerosis: a role for lipids? To better understand the pathogenesis of focal and segmental glomerular hyalinosis and sclerosis (FSGHS), a variety of animal models have been developed--mainly in rats--that allow a comprehensive study of all variables involved, such as hemodynamic, genetic, and metabolic factors. In this article, we briefly review the role of lipids in the pathogenesis of FSGHS and provide evidence that "atherosclerosis of the glomerular mesangium" contributes to the ultimate histopathologic lesion of FSGHS in susceptible rat strains. Observations in a FSGHS-resistant strain revealed several characteristic features that may protect these rats against chronic renal disease such as high nephron numbers, glomerular visceral epithelial cells with a remarkable resistance to toxic injury, minimal sequestration of serum proteins and cholesterol from the circulation into the mesangium, and a remarkable lipoprotein profile in normal as well as nephrotic states with a very low cholesterol content of the very-low-density and low-density lipoprotein fractions. Recent clinicopathologic studies also indicate a correlation between hyperlipidemia and the progression of renal disease. The concept of lipid-mediated glomerular injury warrants further study. 