Nephrotic hyperlipidemia: primary abnormalities in both lipoprotein catabolism and synthesis

One of the most prominent manifestations of the nephrotic syndrome is hyperlipidemia. Lipoprotein synthesis is increased and catabolism is reduced in nephrotic patients and animals. The observation that infusion of either albumin or dextran reduces lipid levels suggests that oncotic pressure (pi) may regulate lipogenesis. It has been postulated that prolonged plasma half-life of lipoproteins in nephrosis is a consequence of saturation of catabolic sites and is secondary to the hyperlipidemia that results from increased lipogenesis. However, the absolute rate of triglyceride catabolism is reduced in nephrotic rats in comparison to normal suggesting that defective lipid catabolism may be a cause rather than a consequence of hyperlipidemia. Furthermore, chylomicrons (CM) and very-low-density lipoproteins (VLDL) are cleared normally in rats with hereditary analbuminemia despite increased lipid synthesis. When we cause proteinuria in analbuminemic rats, the clearance of CM and VLDL becomes greatly prolonged, suggesting that proteinuria, and not reduced serum albumin or pi, is responsible for defective lipoprotein catabolism. Maneuvers that reduce proteinuria, such as administration of an angiotensin-converting enzyme inhibitor, reduce lipid levels in nephrotic patients and animals even when plasma albumin concentration is unchanged supporting a hypothesis that proteinuria may lead to reduced catabolism of lipoproteins.