Effect of Plasma Oncotic Pressure on Apolipoprotein Levels in Rats with Heymann Nephritis

The nephrotic syndrome is characterized by reduced plasma albumin and colloid osmotic pressure (π). Infusion of dextran or albumin reduces lipid levels suggesting that reduced plasma π plays a role in causing hyperlipidemia in the nephrotic syndrome. To determine whether apolipoprotein (Apo) levels were affected by π, passive Heymann nephritis (HN) was created in 20 rats. Hyperoncotic (25%) human albumin or ficoll was infused continuously into each of 5 HN rats adjusted to maintain a plasma π above 20 mm Hg. Either saline or a mixture of amino acids calculated to approximate those released from catabolized human albumin were infused into 5 HN as controls. Urinary rat albumin loss was not different between the 4 groups of HN. Plasma apo A-I, B and E were all increased significantly in saline and amino acid infused HN, but apo A-IV was decreased. Infusion of either albumin or ficoll normalized apo A-I, and apo E levels in HN even though proteinuria continued unabated. In contrast, apo B remained significantly elevated in HN infused with albumin, but was reduced to normal by ficoll. Fifteen non-nephrotic control animals were studied in 3 groups of 5 animals each; one receiving human albumin, one ficoll, both adjusted to increase plasma π to supranormal levels, and a 3rd group received saline. In contrast to HN, plasma apo A-I, E, and B levels were unaffected by albumin or ficoll infusion in control animals. Ficoll caused a significant reduction in apo A-IV in both HN and control animals to subnormal levels, but albumin infusion was without effect. Reduced plasma π, but not reduced plasma albumin is necessary for increased apo A-I, and E levels in the nephrotic syndrome. When plasma π is normal extensive proteinuria does not increase plasma apo A-I or E levels. Factors other than albumin concentration or π, such as persistent urinary protein loss, play a role in establishing increased apo B containing lipoproteins in the nephrotic syndrome. Ficoll may cause changes in plasma lipoprotein levels by means other than its ability to increase plasma π.