Volume 59, Issue 1, Pages 179-189 (January 2001) Hypoalbuminemia and proteinuria contribute separately to reduced lipoprotein catabolism in the nephrotic syndrome1  Gregory C. Shearer, Frazier T. Stevenson, David N. Atkinson, Hardin Jones, Ilona Staprans, George A. Kaysen  Kidney International  Volume 59, Issue 1, Pages 179-189 (January 2001) DOI: 10.1046/j.1523-1755.2001.00478.x Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 1 Plasma very-low density lipoprotein (VLDL) secretion rates in control (▪), Nagase analbuminemic rats (NAR; •), and adriamycin-induced nephrotic syndrome (NS-ADR; ▴). Mean VLDL triglyceride (TG) secretion rates were measured from TG concentration in serum from tail blood of fasted rats following injection of 600 mg/kg Triton WR 1339. (A) Accumulation of serum TG. There are significant differences in the initial TG. The inset represents the average rate of TG accumulation. (B) The accumulation of apoB as a percent of control apoB levels. There are significant differences in initial apoB levels. The inset represents the average rate of apoB accumulation. Error bars represent SEM. †P < 0.05 vs. control. ‡P < 0.05 vs. NAR. Kidney International 2001 59, 179-189DOI: (10.1046/j.1523-1755.2001.00478.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 2 Clearance of chylomicrons (CMs) by hearts from control (▪; t1/2 = 14.8 min), Heymann nephritis-nephrotic syndrome (NS-HN) (▴; t1/2 = 30.2 min†), and Nagase analbuminemic rat (NAR); (•; t1/2 = 33.2 min†). Removal of triglycerides (TG) from CM by isolated perfused hearts. CM labeled with [3H]-trioleate was added to recirculating Krebs buffer to make a final TG concentration of 55 μg/mL. Error bars represent SEM. Clearance is reported here in t1/2, but statistical differences were determined using the rate constant, β (Methods section). †P < 0.05 vs. control. Note log scale of y axis. Kidney International 2001 59, 179-189DOI: (10.1046/j.1523-1755.2001.00478.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 3 Binding of VLDL from control (▪), NAR (•†), and NS-ADR (▴†). Specific binding of VLDL to aortic endothelial cells was measured after five hours using 125I labeled VLDL. (A) Binding to rat aortic endothelial cells (RAECs). (B) Binding to bovine aortic endothelial cells (BAECs). Error bars represent SEM. †P < 0.05 vs. VLDL from control rats. Kidney International 2001 59, 179-189DOI: (10.1046/j.1523-1755.2001.00478.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 4 Binding of VLDL from control (▪) and NS-HN (▴†) Specific binding of VLDL to BAECs was measured after five hours using 125I-labeled VLDL. Error bars represent SEM. †P < 0.05 vs. VLDL from control rats. Kidney International 2001 59, 179-189DOI: (10.1046/j.1523-1755.2001.00478.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 5 Binding of HDL-treated VLDL. HDL protein (0.7 mg) was incubated with 1.0 mg VLDL TG for two hours, and then VLDLs were reisolated. (A) Binding to RAEC of VLDL from NS-ADR incubated with HDL from control (♦‡), NAR (•‡), and NS-ADR (▴) rats. (B) Binding to RAEC of VLDL from control rats incubated with HDL from control (♦‡) and NS-ADR (•). (C) Controls for binding surface and represents binding to BAEC of VLDL from NS-ADR incubated with specific binding of VLDL to aortic endothelial cells was after five hours measured using 125I-labeled VLDL. Error bars represent SEM. ‡P < 0.05 vs. VLDL incubated with nephrotic HDL. Kidney International 2001 59, 179-189DOI: (10.1046/j.1523-1755.2001.00478.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 6 Effect of control HDL on CM clearance in rats with Heymann nephritis. Symbols are: (▴) untreated NS-HN, t1/2 = 43.0 min†; (▵) NS-HN + control HDL, t1/2 = 18.6 min†; (▪) control, t1/2 = 7.1 min. CM labeled with [3H]-trioleate was injected intravenously via the tail vein, and blood was sampled at selected intervals. To determine the effect of control HDL on clearance in NS-HN rats, 7.5 mg of control HDL protein were administered as a bolus to NS-HN rats immediately prior to CM injection. Error bars represent SEM. Clearance is reported here in t1/2, but statistical differences were determined using the rate constant, β (see Methods section). †P < 0.05 vs. control; ‡P < 0.05 vs. control and NS-HN. Note log scale of y axis. Kidney International 2001 59, 179-189DOI: (10.1046/j.1523-1755.2001.00478.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 7 Proposed model of triglyceride (TG) clearance defects in nephrotic and analbuminemic rats describing possible lesions of triglyceride-rich lipoprotein (TRL) catabolism in Nagase analbuminemic rats (NAR) and nephrotic syndrome (NS). Kidney International 2001 59, 179-189DOI: (10.1046/j.1523-1755.2001.00478.x) Copyright © 2001 International Society of Nephrology Terms and Conditions