TY - JOUR
T1 - Proteinuria, lipoproteins and renal apolipoprotein deposits in uninephrectomized female analbuminemic rats
AU - Joles, Jaap A.
AU - Van Goor, Harry
AU - Braam, Branko
AU - Willekes-Koolschijn, Nel
AU - Jansen, Eugène H.J.M.
AU - Van Tol, Arie
AU - Koomans, Hein A.
N1 - Funding Information:
Portions of this work were presented at the American Society of Nephrology in Baltimore (MD, USA) on November 16, 1992 and at an International Symposium on Glomerulonephritis in Bruges (Belgium) on December 4, 1992 and appear in abstract form (JASN 3:741, 1992). This research was supported by the Netherlands Heart Foundation, grant nr. 88.223, the Dutch Kidney Foundation, grant nr, C88,814 and the Dutch Organization for Scientific Research, grant nr. PGS-900-759-233. The plasma apolipoprotein assays, urine protein eleetrophoresis and renal tissue processing were performed by Ms. M.M. Geelhoed-Mieras, Ms. C. Laan and Ms. M.L.C. van der Horst, respectively. Dr. J. Grond evaluated renal histology of the rats used in the mieropuneture experiment. We acknowledge their contributions to this study.
PY - 1995/2
Y1 - 1995/2
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0028901236
U2 - 10.1038/ki.1995.57
DO - 10.1038/ki.1995.57
M3 - Article
C2 - 7723232
AN - SCOPUS:0028901236
SN - 0085-2538
VL - 47
SP - 442
EP - 453
JO - Kidney International
JF - Kidney International
IS - 2
ER -