Uremia-specific alterations in lipid metabolism

Uremic patients suffer from a secondary form of complex dyslipidemia consisting of quantitative and qualitative abnormalities in serum lipoproteins resulting in altered lipoprotein composition and metabolism. The most prominent are an increase in serum triglyceride levels (due to elevated very-low-density lipoprotein remnants and intermediate-density lipoprotein) and low high-density lipoprotein (HDL) cholesterol. Low-density lipoprotein (LDL) cholesterol is often normal, but the cholesterol may originate from the atherogenic small and dense LDL subclass. The apolipoprotein B-containing part of the lipoprotein may undergo modifications (peptide modification of the enzymatic and advanced glycation end-product, oxidation or glycosylation). Modifications contribute to impaired LDL receptor-mediated clearance from plasma and promote prolonged circulation. HDL particles are structurally altered during states of inflammation. The contribution of this complex and atherogenic form of dyslipidemia to cardiovascular disease in patients with renal disease is at present unclear. Most studies are negative in demonstrating the predictive power of serum lipids for the development of cardiovascular disease. This is most likely due to interference with deteriorating aspects of the activated acute-phase response. Since it is also still unclear whether we have therapeutics available with a sufficient impact on LDL size, remnant lipoprotein lowering and restoration of HDL function, we urgently need specific intervention trials.