High density lipoproteinuria in nephrotic syndrome

Intravenous administration of the aminonucleoside of puromycin produces the nephrotic syndrome (proteinuria, hypercholesterolemia, hypoproteinemia and edema) in rats. This model is very similar to human nephrotic syndrome caused by various disease states. The current study was designed to assess the nature of urinary lipoproteins in the urine of nephrotic rats, including studies related to the urinary loss of the "activator" apolipoproteins for the lipoprotein lipase-triglyceride interaction. Sprague-Dawley rats were given a single intravenous injection (10 mg/100 g) of puromycin aminonucleoside. Plasma and urine were collected before and 7, 18, 29, 36, and 53 days after injection of puromycin. Urine was fractionated in the preparative ultracentrifuge into density (d) fractions less than 1.006 (very low-density lipoproteins), d = 1.006-1.063 (low-density lipoproteins), and d = 1.063-1.210 (high-density lipoproteins--HDL). The cholesterol, triglyceride, phospholipid, and protein content of these fractions was analyzed. Lipoprotein electrophoresis was performed in agarose agar. Urine from normal and nephrotic rats was added to an in vitro system containing lipoprotein lipase and triglyceride. The free fatty acids (FFA) liberated were then measured as an index of urinary activator property on this system. Measurable urinary lipoproteins were present only on days 7 and 18 after induction of the nephrotic syndrome. Coelectrophoresis of these urinary lipoproteins with rat plasma revealed a single band having alpha- (HDL) electrophoretic mobility. The total mean protein content of day-7 urinary lipoproteins (64.3%) was greater than the content of plasma HDL (52.9%). The protein content of urinary lipoproteins also increased with time. When day-7 and day-18 postinjection urine at nephrotic rats was added to the lipoprotein lipase system, the hydrolysis of triglyceride yielded a mean of 0.320 and 0.235 muEq FFA/ml/20 min, respectively. Control rat urine yielded 0.030 muEq FFA/ml/20 min and 0.000 muEq FFA/ml/20 min 7 and 18 days after injection of normal saline, respectively. It is inferred that in this experimental model (1) high-density lipoproteins are probably excreted in the glomerular filtrate, (2) alterations in the composition of the excreted lipoproteins may occur during their passage through the nephron. The possibility that only a selective portion of the HDL spectrum is excreted into the glomerular filtrate cannot be excluded. It is suggested that the urinary or renal loss of this functionally important lipoprotein may contribute to the pathophysiology of hyperlipoproteinemia in the nephrotic syndrome.