title: In vivo kinetic studies to further understand pathogenesis of abnormal lipoprotein metabolism in chronic kidney disease.
abstract: Patients undergoing hemodialysis (HD) have been shown to be at increased risk for cardiovascular disease (CVD) morbidity and mortality which are, at least in part, due to uremic dyslipidemia including increased triglyceride-rich lipoproteins, in particular remnants, decreased high-density lipoprotein (HDL), and increased lipoprotein(a) [Lp(a)]. In vivo kinetic studies using stable isotope revealed that apolipoprotein (apo)A-I, a primary apoprotein constitute of HDL, was catabolized at a faster rate in HD patients, leading to decreased apoA-I, and therefore reduced HDL cholesterol concentrations. Likewise, apoB catabolic rates were significantly lower in intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) apoB; the latter is also accompanied by a decreased production rate. In HD patients, IDL apoB levels were elevated, but LDL apoB levels remained within the normal range. Nonetheless, a prolonged residence time for LDL apoB of 2-5 days, made LDL more atherogenic. Atorvastatin completely ameliorated impaired LDL apoB catabolism. With regard to Lp(a) metabolism, both apoB and apo(a) were found to be slowly catabolized, indicating roles of normal kidney function on Lp(a) catabolism. Finally, a compartmental model suggests intracellular, rather than extracellular, assembly of Lp(a). This in vivo kinetic evidence will uncover the underlying mechanism for uremic dyslipidemia and provide strategies to reduce CVD in HD patients.
authors.affiliation: Division of Anti-Aging, Vascular Medicine, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513, Japan, katsunorike@ndmc.ac.jp.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikewaki
mesh_terms: D016632:Apolipoprotein A-I / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D050197:Atherosclerosis; D002318:Cardiovascular Diseases / Q000517:prevention & control; D008076:Cholesterol, HDL / Q000378:metabolism; D050171:Dyslipidemias / Q000503:physiopathology; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000378:metabolism*; D006435:Renal Dialysis / Q000009:adverse effects*; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008074:Lipoproteins