Pathogenesis of hyperlipidemia in the nephrotic syndrome

Both increased synthesis and decreased clearance of lipoproteinemia may contribute to the hyperlipoproteinemia which frequently complicates the nephrotic syndrome with increased levels of total and low-density lipo-protein (LDL) cholesterol as the most characteristic abnormality. The hyperlipoproteinemia may also be characterized by elevated levels of triglycerides, increased concentrations of Apo B, Apo C and Apo E and reduced levels of Apo A-I and Apo A-II. The increased lipoprotein synthesis occurs in partly undefined mechanisms related to proteinuria, hypoalbuminemia and, possibly, increased availability of mevalonate as a substrate for cholesterol synthesis. Urinary loss of high-density lipoprotein (HDL) components and other liporegulatory factors may contribute to decreased activity of lipolytic enzymes and result in impaired clearance of cholesterol- and triglyceride-rich lipoproteins of lower densities and altered composition of HDL. The variability in these two metabolic abnormalities may account for the corresponding variability in lipoprotein profiles of patients with the nephrotic syndrome.