Abnormalities in uremic lipoprotein metabolism and its impact on cardiovascular disease

Patients with end-stage renal disease (ESRD) suffer from a secondary form o f complex dyslipidemia consisting of both quantitative and qualitative abno rmalities in serum lipoproteins resulting from alterations in lipoprotein m etabolism and composition. The prominant features of uremic dyslipidemia ar e an increase in serum triglyceride levels (due to elevated very low densit y lipoprotein [VLDL]-remnants and intermediate-density lipoprotein [IDL]) a nd low high-density lipoprotein (HDL) cholesterol. Low-density lipoprotein (LDL) cholesterol often is normal, but the cholesterol may originate from t he atherogenic small and dense LDL subclass (sdLDL). The apolipoprotein B ( apoB)-containing part of the lipoprotein may undergo modifications (enzymat ic- and advanced glycation end-product [AGE]-peptide modification, oxidatio n, or glycosilation). Modifications contribute to Impaired LDL receptor-med iated clearance from plasma and promote prolonged circulation. While LDL pa rticles undergo a vicious cycle of accumulation and modification, reverse c holesterol transport is also impaired due to low lecithin:cholesterol acylt ransferase (LCAT) and paraoxonase activity. Therefore, discoid HDL particle s are structurally altered and hepatic cholesterol clearance is limited. Th e composition of HDL may also be altered during states of inflammation. The contribution of this complex and atherogenic form of dyslipidemia to cardi ovascular disease in patients with renal disease is unclear at present. Mos t studies are negative in demonstrating the predictive power of serum lipid s for the development of cardiovascular disease. This Is most likely due to interference with deteriorating aspects of the activated acute-phase respo nse. Nevertheless, patients with renal disease belong to a very high cardio vascular risk group and dyslipidemia should most likely be subjected to suf ficient lipid-lowering therapy in most patients. Because it is also still u nclear whether we have available therapies with sufficient impact on LDL si ze, remnant lipoprotein-lowering, and restoration of HDL function, we urgen tly need the results from large scale intervention trials such as the 4D-tr ial and the CHORUS study. (C) 2001 by the National Kidney Foundation, Inc.