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 dis ease than female rats. However, female Nagase analbuminemic rats (NAR) are profoundly hyperlipidemic and develop proteinuria and glomerulosc lerosis after uninephrectomy. Male NAR are less hyperlipidemic and are resistant to developing renal damage after uninephrectomy. Ovariectom y markedly decreases hepatic triglyceride secretion and plasma triglyc eride levels in the female NAR. EXPERIMENTAL DESIGN: In this study, we investigated the relationship between plasma lipids and lipoprotein c omposition as well as the development of proteinuria, glomerular apoli poprotein and lipid deposition, and glomerulosclerosis in aging female and male analbuminemic rats. We also studied whether ovariectomy in f emale NAR at an early age would protect their renal function in old ag e.RESULTS: Aging hyperlipidemic female NAR with high triglyceride and cholesterol levels in very low density lipoprotein (VLDL) and intermed iate density lipoprotein (IDL) were found to develop spontaneous prote inuria at 9 months of age. Glomerular lipid deposition and glomerulosc lerosis 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 p ersistent decreases in triglyceride and cholesterol content of VLDL an d IDL as well as total plasma triglycerides, without much change in LD L, high density lipoprotein, total plasma cholesterol, or apolipoprote in B, and they remained completely free of proteinuria and glomerulosc lerosis. Apolipoprotein B deposition in glomeruli was not different in the oldest female, male, or ovariectomized NAR No important differenc es were observed in glomerular diameter between the three different gr oups up to the age of 1 year. CONCLUSIONS: These findings point to an important role of elevated lipid content of the triglyceride-rich lipo proteins VLDL and IDL in the pathogenesis of proteinuria and glomerulo sclerosis in the female NAR.