Dyslipoproteinaemia is an important risk factor for the development of atherosclerosis in noninsulin-dependent diabetes mellitus (NIDDM). This study shows that the uptake of low-density lipoproteins (LDLs) prepared from the plasma of patients with NIDDM in cultured human hepatoma cells is largely reduced. In addition, diabetic LDL was less effective in suppressing intracellular cholesterol synthesis. This is because of physicochemical and biochemical differences between lipoproteins from diabetic and from normal individuals. LDL from patients with NIDDM was abnormal with regard to charge, the degree of glycation, the lipid composition and the conformation of the apolipoprotein B receptor-binding domain. The diminished receptor-mediated uptake of apolipoprotein B-containing lipoproteins in diabetic individuals most probably leads to the accumulation of these lipoproteins in vivo and may be of great importance to the pathogenesis of atheroclerosis in these patients.

Lp(a) and oxLp(a) induce the activation of ROM in glomeruli by a pathway that is sensitive to inhibition of protein kinase C and elevation of intracellular CAMP levels.

We conclude that glomerular epithelial and mesangial cells as well as skin fibroblasts and HepG2 exhibit VLDL receptors additionally to their LDL receptors, even though the regulation of the VLDL receptor in HepG2 cells seems to differ from the regulation in glomerular epithelial and mesangial cells. The high degradation-uptake-ratio in these renal cells suggests the presence of an effective clearance pathway which might serve as protection against lipoprotein accumulation.

No abstract

Dyslipidemia of chronic renal failure is of multifactorial origin. Decreased activity of lipoprotein lipase and hepatic triglyceride lipase, peripheral insulin resistance, hyperparathyroidism and L-carnitine deficiency are the contributing factors. This results in a disturbed catabolism of chylomicron, accumulation of very-low-density (VLDL) and intermediate-density (IDL) lipoproteins as well as incompletely cleared remnant particles, whereas low-density lipoprotein (LDL) levels are diminished. There is current debate as to whether cardiovascular disease is accelerated and whether hyperlipidemia should specifically be treated. In addition, there have been few means of influencing these metabolic alterations. Drug incompatibility and consequently side effects render treatment difficult. The drugs that have been most tested for lipid lowering in chronic renal failure are the fibric acids. By their mode of action, they are the logical choice. Dose reduction overcomes major side effects such as myopathy and rhabdomyolysis. The second generation of fibric acid derivatives (gemfibrozil and beclobrate) show several advantages over formerly used derivatives. Treatment with lovastatin and simvastatin appears to be safe and is recommended in a minority of patients with predominantly elevations of LDL. HMG-CoA reductase inhibitors also lower remnant particles effectively in hemodialysis (HD) patients. L-Carnitine and low-molecular-weight heparin have been shown to influence VLDL rich in triglycerides in a subset of patients on HD. In posttransplant hyperlipidemia, diet remains the first course of action in all patients. When this approach fails, the new lipid-lowering agents, especially fibric acids, appear to be safe in short-term studies in azathioprine- and ciclosporin-treated patients. Lovastatin has been shown to be safe in stable renal transplant patients. Its toxicity seems to depend mainly on high ciclosporin whole blood through or plasma levels.