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Hypoalbuminemia and proteinuria contribute separately to reduced lipoprotein catabolism in the nephrotic syndrome.
Kidney Int. 2001 Jan; 59(1):179-89.KI

Abstract

BACKGROUND

Hypertriglyceridemia is a result of reduced triglyceride (TG)-rich lipoprotein (TRL) catabolism and occurs in rats with nephrotic syndrome (NS) and in Nagase analbuminemic rats (NARs). While the heparin-releasable lipoprotein lipase (LpL) pool in NAR and in NS is similar, TG levels are significantly greater in NS, suggesting that factors other than reduced LpL alone act in NS but not in NARs. Furthermore, clearance of chylomicrons (CM) and very low-density lipoprotein (VLDL) is normal in vivo in NAR despite low LpL levels. We tested the hypotheses that impaired binding of VLDL and impaired VLDL-high density lipoprotein (HDL) interactions contribute to hyperlipidemia in NS.

METHODS

TG and apoB secretion was measured using Triton WR 1339. Clearance of CMs by perfused hearts from NS and NAR was determined. Binding of VLDL from control, NS and NAR to rat aortic endothelial cells (RAECs) was measured prior to and following incubation with HDL from NS, NARs, and control. ApoE, protein, and TG content was determined.

RESULTS

TG levels were greatest in NS (516 +/- 95 mg/dL), intermediate in NAR (193 +/- 20), and least in control (97 +/- 16, P = 0.05), while in contrast, TG secretion was least in NS (178 +/- 33 mg/dL/hour) versus 212 +/- 17 in NAR and 294 +/- 15 in control (P < 0.001 vs. NS). Clearance of CMs by NS and NAR hearts was the same and significantly reduced versus control (P < 0.005). Binding of NS-VLDL to endothelial cells was reduced, while NAR-VLDL binding was increased versus control (P < 0.001). Incubation of NS-VLDL with control or NAR HDL increased VLDL binding compared with binding following incubation with NS HDL (P < 0.001).

CONCLUSION

Increased TG levels in both NS and NAR are the result of decreased TRL clearance. TG levels are greater in NS because of the presence of a combined defect: (1) a decrease in endothelial-bound LpL that occurs as a consequence of reduced serum albumin concentration, and (2) a defect in VLDL binding to endothelial-bound LpL. This latter defect occurs only in the presence of proteinuria and is conferred by HDL.

Authors+Show Affiliations

Division of Nephrology, Department of Medicine, UC Davis, Davis, CA 95616, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

11135070

Citation

Shearer, G C., et al. "Hypoalbuminemia and Proteinuria Contribute Separately to Reduced Lipoprotein Catabolism in the Nephrotic Syndrome." Kidney International, vol. 59, no. 1, 2001, pp. 179-89.
Shearer GC, Stevenson FT, Atkinson DN, et al. Hypoalbuminemia and proteinuria contribute separately to reduced lipoprotein catabolism in the nephrotic syndrome. Kidney Int. 2001;59(1):179-89.
Shearer, G. C., Stevenson, F. T., Atkinson, D. N., Jones, H., Staprans, I., & Kaysen, G. A. (2001). Hypoalbuminemia and proteinuria contribute separately to reduced lipoprotein catabolism in the nephrotic syndrome. Kidney International, 59(1), 179-89.
Shearer GC, et al. Hypoalbuminemia and Proteinuria Contribute Separately to Reduced Lipoprotein Catabolism in the Nephrotic Syndrome. Kidney Int. 2001;59(1):179-89. PubMed PMID: 11135070.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypoalbuminemia and proteinuria contribute separately to reduced lipoprotein catabolism in the nephrotic syndrome. AU - Shearer,G C, AU - Stevenson,F T, AU - Atkinson,D N, AU - Jones,H, AU - Staprans,I, AU - Kaysen,G A, PY - 2001/1/3/pubmed PY - 2001/3/7/medline PY - 2001/1/3/entrez SP - 179 EP - 89 JF - Kidney international JO - Kidney Int. VL - 59 IS - 1 N2 - BACKGROUND: Hypertriglyceridemia is a result of reduced triglyceride (TG)-rich lipoprotein (TRL) catabolism and occurs in rats with nephrotic syndrome (NS) and in Nagase analbuminemic rats (NARs). While the heparin-releasable lipoprotein lipase (LpL) pool in NAR and in NS is similar, TG levels are significantly greater in NS, suggesting that factors other than reduced LpL alone act in NS but not in NARs. Furthermore, clearance of chylomicrons (CM) and very low-density lipoprotein (VLDL) is normal in vivo in NAR despite low LpL levels. We tested the hypotheses that impaired binding of VLDL and impaired VLDL-high density lipoprotein (HDL) interactions contribute to hyperlipidemia in NS. METHODS: TG and apoB secretion was measured using Triton WR 1339. Clearance of CMs by perfused hearts from NS and NAR was determined. Binding of VLDL from control, NS and NAR to rat aortic endothelial cells (RAECs) was measured prior to and following incubation with HDL from NS, NARs, and control. ApoE, protein, and TG content was determined. RESULTS: TG levels were greatest in NS (516 +/- 95 mg/dL), intermediate in NAR (193 +/- 20), and least in control (97 +/- 16, P = 0.05), while in contrast, TG secretion was least in NS (178 +/- 33 mg/dL/hour) versus 212 +/- 17 in NAR and 294 +/- 15 in control (P < 0.001 vs. NS). Clearance of CMs by NS and NAR hearts was the same and significantly reduced versus control (P < 0.005). Binding of NS-VLDL to endothelial cells was reduced, while NAR-VLDL binding was increased versus control (P < 0.001). Incubation of NS-VLDL with control or NAR HDL increased VLDL binding compared with binding following incubation with NS HDL (P < 0.001). CONCLUSION: Increased TG levels in both NS and NAR are the result of decreased TRL clearance. TG levels are greater in NS because of the presence of a combined defect: (1) a decrease in endothelial-bound LpL that occurs as a consequence of reduced serum albumin concentration, and (2) a defect in VLDL binding to endothelial-bound LpL. This latter defect occurs only in the presence of proteinuria and is conferred by HDL. SN - 0085-2538 UR - https://www.unboundmedicine.com/medline/citation/11135070/Hypoalbuminemia_and_proteinuria_contribute_separately_to_reduced_lipoprotein_catabolism_in_the_nephrotic_syndrome_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(15)47452-6 DB - PRIME DP - Unbound Medicine ER -