In Vivo Studies of the Role of Albumin in Endogenous and Heparin-Activated Lipemia-Clearing in Nephrotic Rats 1

Abstract

In a previous study (1) heparin was found to inhibit the rise of plasma lipids and cholesterol occurring in rats with nephrosis experimentally induced by injection of anti-rat kidney serum (AKS). Such inhibition was marked when heparin was administered prior to and immediately after the injection of AKS, but of much lesser degree when administered to the chronic nephrotic rat with established hypoalbuminemia and hyperlipemia. A similar slight or absent anti-lipemic response to heparin has been observed in some human subjects with nephrosis (2). This suggested to us that perhaps the inhibitory action of heparin necessitated the presence of a larger concentration of plasma albumin than was present in the chronic nephrotic rat.Therefore a second study (3) was done in which bovine serum albumin was infused into rats during both the induction and chronic phases of experimental nephrosis. This was found to be far more effective than heparin in respectively preventing and correcting the hyperlipemia otherwise occurring in such rats. However, the infusion of albumin was not found capable of completely normalizing the plasma lipids of the nephrotic animal unless it concomitantly was nephrectomized.This suggested that the accumulation of lipids in the plasma of the nephrotic rat is due not only to a quantitative deficiency of plasma albumin (3) but also to the excessive renal loss of some other essential plasma constituent of the lipid-clearing mechanism which might be escaping pan passu, either separately or combined with the escaping albumin. If this substance were heparin, or its plasma equivalent, the combined administration of heparin and albumin would be expected to be 'Aided by Grants from the National Institute of Arthritis and Metabolic Diseases of the National Institutes of Health, (A-46, C-4), the American Heart Association and the San Francisco Heart Association.completely effective in normalizing the plasma lipids of the nephrotic rat. This was found to be true in the present study of such combined treatment, the data also providing an in vivo demonstration of the essential role of adequate plasma albumin for both endogenous and heparin-activated processes of lipemia-clearing. METHODS AND RESULTSAdult, male rats (Long-Evans) were used in these studies. Pooled rabbit anti-rat kidney serum (AKS) was prepared as described by Heymann and Lund (4) and assayed in preliminary studies by its ability to induce hypoalbuminemia, hyperlipemia and hypercholesteremia within 18 hours after its intravenous injection. Continuous intravenous infusions were administered by a special constant infusion apparatus designed to inject 0.25 ml.per hour (6.0 ml. per 24 hours) through an exteriorized polyethylene cannula placed in an inferior lumbar vein during a preliminary operation accomplished under ether anesthesia. The injected solutions were either freshly prepared aqueous bovine serum albumin (30 per cent) or sodium chloride (0.9 per cent), the latter being used since it was previously found to induce a degree of hemodilution in...

Plasma Lipid Interrelationships in Experimental Nephrosis1

“…Our studies also indicated that the accumulation of cholesterol in the plasma in this syndrome is not caused by any preceding change in its intestinal absorption (2) or excretion (3), or in the rate of its hepatic synthesis (6). Finally, it was found that both the hyperlipemia and the hypercholesteremia were initiated by the loss of albumin and, conversely, were remedied by the administration of albumin (8,13) particularly in conjunction with heparin (12). (15), when phosphatide was infused in an amount sufficient to further raise the plasma phospholipid concentration, the resulting plasma levels were notably disproportionate.…”

Studies on the Metabolism of Plasma Proteins in the Nephrotic Syndrome. Ii. The Lipoproteins12

“…It has also been observed, however, that children with the nephrotic syndrome show varying degrees of lipoprotein lipase deficiency (31) ; Rosenman and Friedman have recently reported similar findings in nephrotic rats (32). It has been found that in some nephrotic children, hypercholesterolemia was due primarily to an elevation of lipoproteins of Sf 3 to 9, but, in these instances, the Sf 10 to 200 lipoproteins were also elevated (33, …”

Cutaneous and Tendon Xanthomas

“…There is a prim ary form known as lipid nephrosis, although a similar picture may develop during chronic glomerulonephritis, Kimmelstiel-Wilson syndrome, amyloidosis, toxic or allergic reactions, infections, renal vein thrombosis, lupus erythem atosus and multiple myeloma. The mechanism of the hyperlipemia is partly explained by the severe de pletion of serum albumin which seems to be necessary for transport of free fatty acids, and also because of the loss of a factor which may play an im portant role in the clearing process of lipids from the blood [9,43,44]. E ruptive xanthom as have been recorded accompanying the nephrotic syndrome, although their incidence seems to be low [20,46], Recovery from the nephrotic syndrome is followed by nor malization of lipid levels and disappearance of skin xanthom as.…”