Plasma and urine lipoproteins during the development of nephrotic syndrome induced in the rat by adriamycin.

The changes of plasma lipoproteins which occur during the development of nephrotic syndrome induced in the rat were investigated by the administration of the antineoplastic drug adriamycin. Rats received a single intravenous injection of the drug (7.5 mg/Kg) and were sacrificed 5, 10, 15, 20, 25, and 30 days after treatment. By monitoring plasma and urine albumin, four stages in the development of nephrosis were identified: (1) a prenephrotic stage, (2) a mild nephrosis with moderate albuminuria and hypoalbuminemia; (3) a severe nephrosis with massive albuminuria and severe hypoalbuminemia; and (4) a recovery stage in which plasma albumin showed the tendency to increase. Apart from a mild elevation of plasma triacylglycerols and VLDL observed as early as Day 5, no changes in plasma cholesterol and in the other lipoprotein classes were observed at the stage of mild nephrosis (Day 10). However, as the disease became more severe (Day 15-25) there was a striking increase of HDL1 (1.050-1.090 g/ml) and, above all, of HDL2 (1.090-1.210 g/ml). VLDL and LDL also increased but at a later stage. The elevation of HDL1 and HDL2 was associated with an increase of apolipoprotein A-I in plasma (fourfold increase). Moreover, the relative content of this apolipoprotein in HDL1 and HDL2 increased as the disease progressed from mild to severe, so that in severely nephrotic rats HDL1 and HDL2 contained almost exclusively A-I and C apolipoproteins. HDL enriched in apolipoprotein A-I were also found in urine of severely nephrotic animals. Since these findings are similar to those previously described in nephrotic syndrome induced by puromycin aminonucleoside (Gherardi, E., and Calandra, S. (1982). Biochim. Biophys. Acta 710, 188.) the following conclusions can be drawn: (1) the key signs of nephrotic syndrome (albuminuria and hypoalbuminemia) precede the elevation of plasma lipoproteins; (2) the pattern of nephrotic hyperlipoproteinemia evolves as a function of the severity of the disease; (3) the accumulation of HDL enriched in apolipoprotein A-I represents an early and specific feature of nephrotic hyperlipoproteinemia in the rat