Nephrotic hyperlipidemia: is inhibition of receptor- mediated edocytosis involved?
Tzanko S. Stantchev
Hyperlipidemia is a consistent feature of the nephrotic syndrome (NS) and is usually of the Ha or lib Fredrickson type. In cases with severe hypoalbuminemia (15g/l or less) very low density lipoproteins (VLDL) also increase and the ratio of cholesterol to.triglyceride falls (1-4). The nephrotic hyperlipidemia is generally considered to be due to increased hepatic synthesis and secretion of lipoproteins, but there are also investigations showing altered lipoprotein clearance (1,2). Warwick et al. (5) have found a trend towards lower fractional catabolic rate of intermediate density lipoproteins (IDL) and low density lipoproteins (LDL) in nephrotic patients with relatively well maintained serum albumin despite the heavy proteinuria. In another group of nephrotic pateints with lower plasma albumin levels, the amount of LDL cleared by receptormediated endocytosis (RME) was only 55% of the value seen in controls, while 60% more LDL were channeled into alternative catabolic pathways (6). In experimental NS, delayed removal of chylomicron remnants was revealed as well (7). Chylomicron remnants are taken up by the liver via the LDL receptor-related protein (LRP). Recently, evidences were provided that receptor for activated x,-macroglobulin (a 2 macroglobulin-proteinase complex) and the LRP are one and the same entity (8). x, macroglobulin seems to control the activity of proteinases not by active site-directed inhibition but by steric shelding and rapid clearance (9). The plasma levels of a 2 -macroglobulin are consistently elevated in NS (2), but to the best of my knowledge, there are insufficient data about the uptake of oc 2 -macroglobu- lin-proteinase complexes. Asamietal. (10) reported a glomerular deposition of a 2 -macroglobulin in a child with steroid refractory NS, but such depositions were not detected in other nephrotic patients. Biochemical and clinical improvement was observed in this case after treatment with the synthetic proteinase inhibitor camostat mesylate, but the dynamics of a 2 -macroglobulin depositions was not examined.
Biomed Rev 1994; 3: 77-79.