[Frontiers in Bioscience 7, e326-338, August 1, 2002]


Julian B. Marsh

Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA, USA, 02111


1. Abstract
2. Introduction
3. Discussion
3.1. Albumin metabolism
3.2. Lipoprotein metabolism
3.2.1. VLDL Metabolism
3.2.2. Chylomicron Metabolism
3.2.3. LDL Metabolism
3.2.4. Lipoprotein (a)
3.2.5. HDL and apoA-I Metabolism
3.3. Receptors
3.3.1. Effects of Statins
3.4. Lipid transfer (LCAT and CETP)
3.5. Lipases (Lipoprotein and Hepatic)
3.6. Lipid metabolism
3.7. Lipiduria
3.8. Hypotheses and questions
3.8.1. Is the initiating event hepatic overproduction of lipoproteins?
3.8.2. Is the initiating event decreased lipolysis of triglyceride-rich lipoproteins?
3.8.3. Why does impaired clearance of triglyceride-rich lipoproteins accompany nephrosis?
3.8.4. Is there an explanation for a decrease in lipase activity?
3.9. Summary
4. Acknowledgment
5. References


This review covers lipids, apolipoproteins, and receptors involved in the dyslipidemia of the nephrotic syndrome in humans and in rat or mouse models of the syndrome. It emphasizes research published during the last decade, though earlier work is cited. The focus is on the biosynthesis and catabolism of the plasma lipoprotein density classes and the role of receptors and enzymes in regulating lipoprotein metabolism in nephrosis. Although the factors responsible for the initiation of the hepatic and peripheral cellular responses to proteinuria and hypoalbuminemia remain elusive, recent work highlights the increased risk of atherosclerosis and the progression of renal disease associated with nephrotic dyslipidemia. Understanding of the role of the kidney in the catabolism of apolipoproteins entering the glomerular filtrate has been enhanced by the discovery of the receptor-mediated uptake of apolipoprotein A-I, the main apoprotein of HDL. The following aspects of lipid and lipoprotein metabolism in relation to nephrosis are discussed, with attention paid to differences between experimental nephrosis and the human nephrotic syndrome:(1) Albumin metabolism (2) Lipoprotein metabolism (3) Receptors (4) LCAT and CETP (5) Hepatic and Lipoprotein Lipase (6) Lipid metabolism (7) Lipiduria (8) Hypotheses and Questions (9) Summary.