Glomerular Hyalinosis in Relation to Lipid Deposition in Rats with Reduced Renal Mass

Abstract

Studies have suggested that similarities exist between the pathogenesis of glomerulosclerosis and atherosclerosis. The role of subendothelial accumulation of macromolecular substances, lipids in particular, in the pathogenesis of glomerular hyalinosis and sclerosis was studied in 17 Sprague-Dawley rats with reduced renal mass (1 and 1/3 nephrectomy). Sequential changes of functional and morphologic data were studied three, five and seven months after ablation. Urinary protein excretion, and values for blood urea nitrogen, creatinine, fasting serum cholesterol, and triglycerides all increased by the third month following operation. After the seven months, the rats had a significantly higher daily urine protein excretion than animals at month 3 and greater values for fasting serum cholesterol and triglycerides than animals at month 5. By light microscopy, animals at month 7 showed a significantly greater percentage of glomeruli with segmental hyalinosis/sclerosis than rats at month 3. Glomerular lipid deposition, confirmed by oil red 0 staining, was noted in 11 animats (65%). Ultrastructurally, a subendothelial accumulation of fat and electron- dense proteinaceous material, which corresponded to the early hyalinosis lesion in glomeruli, was observed more frequently in rats at month 7 than in animals at months 3 and 5. Mesangial deposition of the same substances was seen in nine rats showing no significant difference in each group. These observations suggest that the development of glomerular hyalinosis may be related to the subendothelial deposition of harmful lipids in the circulation, similar to arterial wall damage in atherosclerosis, eventually leading to glomerular sclerosis.