High lipid levels in very low density lipoprotein and intermediate density lipoprotein may cause proteinuria and glomerulosclerosis in aging female analbuminemic rats.

BACKGROUND: Male rats are generally more prone to developing renal disease than female rats. However, female Nagase analbuminemic rats (NAR) are profoundly hyperlipidemic and develop proteinuria and glomerulosclerosis after uninephrectomy. Male NAR are less hyperlipidemic and are resistant to developing renal damage after uninephrectomy. Ovariectomy markedly decreases hepatic triglyceride secretion and plasma triglyceride levels in the female NAR. EXPERIMENTAL DESIGN: In this study, we investigated the relationship between plasma lipids and lipoprotein composition as well as the development of proteinuria, glomerular apolipoprotein and lipid deposition, and glomerulosclerosis in aging female and male analbuminemic rats. We also studied whether ovariectomy in female NAR at an early age would protect their renal function in old age. RESULTS: Aging hyperlipidemic female NAR with high triglyceride and cholesterol levels in very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) were found to develop spontaneous proteinuria at 9 months of age. Glomerular lipid deposition and glomerulosclerosis were observed at 18 months of age. In male NAR that had lower lipid levels in VLDL and IDL, only mild proteinuria and no glomerular lipid deposition or glomerulosclerosis were observed up to the age of 22 months. Concurrently ovariectomized NAR demonstrated profound and persistent decreases in triglyceride and cholesterol content of VLDL and IDL as well as total plasma triglycerides, without much change in LDL, high density lipoprotein, total plasma cholesterol, or apolipoprotein B, and they remained completely free of proteinuria and glomerulosclerosis. Apolipoprotein B deposition in glomeruli was not different in the oldest female, male, or ovariectomized NAR. No important differences were observed in glomerular diameter between the three different groups up to the age of 1 year. CONCLUSIONS: These findings point to an important role of elevated lipid content of the triglyceride-rich lipoproteins VLDL and IDL in the pathogenesis of proteinuria and glomerulosclerosis in the female NAR.