Proteinuria, lipoproteins and renal apolipoprotein deposits in uninephrectomized female analbuminemic rats

Abstract

To elucidate the pathogenetic role of hyperlipidemia per se in the development of glomerulosclerosis, severely hyperlipidemic female analbuminemic rats (NAR) and mildly hyperlipidemic male NAR were studied for a period of 37 weeks after uninephrectomy (UNX). Plasma cholesterol increased from 6.3 ± 0.4 (week 4) to 11.9 ± 0.6 mmol/liter (week 37) in the ♀ NAR, and from 4.3 ± 0.1 to 6.4 ± 0.5 mmol/liter in the ♂ NAR in the same period. Plasma protein concentration was also consistently higher in ♀ NAR (60 ± 1 g/liter) as compared to ♂ NAR (52 ± 1 g/liter). Plasma viscosity was higher in ♀ NAR than in ♂ NAR, but there were no differences in blood viscosity. Proteinuria increased progressively in the UNX ♀ NAR from 25 weeks after surgery, reaching a final value of 141 ± 37 mg/day. No proteinuria occurred in the UNX ♂ NAR (final value 15 ± 2 mg/day). Glomerular capillary pressure, measured prior to the onset of proteinuria, was not significantly different in UNX ♀ NAR and UNX ♂ NAR. At the end of the study glomerulosclerosis and lipid deposition was only found in the UNX ♀ NAR. Throughout the study hyperfiltration and hyperperfusion, relative to the one-kidney clearances of the sham-operated (2K) animals, were not different in UNX ♂ and ♀ NAR. No differences were observed in blood pressure. Hypertrophy, evaluated by glomerular diameters, was less pronounced in UNX ♀ NAR (174 ± 3 μm) than in UNX ♂ NAR (190 ± 7 μm). Glomerular diameters in 2K ♀ and ♂ NAR were similar (respectively 158 ± 2 and 157 ± 4 μm). Plasma apo B levels were similar (2K ♀ NAR: 204 ± 8 U; 2K ♂ NAR 204 ± 13 U), but cholesterol and triglyceride content of apo B-containing lipoproteins, namely VLDL, IDL and LDL, was increased twofold in the ♀ NAR as compared to the ♂ NAR, implying a larger particle size in the ♀ NAR. Deposition of apo B and apo E was observed in the glomerular mesangium of UNX ♀ NAR, particularly in sclerotic lesions. Glomerular apo A-I deposits were localized primarily in visceral epithelial cells and were not associated with sclerotic lesions. The development of proteinuria and glomerulosclerosis after UNX in ♀ NAR but not in ♂ NAR may depend upon differences in plasma lipoprotein composition, but is apparently not related to differences in whole kidney hyperfiltration and hyperperfusion, glomerular capillary pressure, or blood viscosity.