title: Plasma apolipoprotein C-III metabolism in patients with chronic kidney disease.
abstract: Moderate chronic kidney disease (CKD) (defined by an estimated glomerular filtration rate of 30-60 ml/min) is associated with mild hypertriglyceridemia related to delayed catabolism of triglyceride-rich lipoprotein particles. Altered apolipoprotein C-III (apoC-III) metabolism may contribute to dyslipidemia in CKD. To further characterize the dyslipidemia of CKD, we investigated the kinetics of plasma apoC-III in 7 nonobese, nondiabetic, non-nephrotic CKD subjects and 7 age- and sex-matched healthy controls, using deuterated leucine ([5, 5, 5, ²H₃]leucine), gas chromatography-mass spectrometry, and multicompartmental modeling. Compared with controls, CKD subjects had higher concentrations of plasma and VLDL triglycerides and plasma and VLDL apoC-III (P < 0.05). The increased plasma apoC-III concentration was associated with a decreased apoC-III fractional catabolic rate (FCR) (1.21 ± 0.15 vs. 0.74 ± 0.12 pools/day, P = 0.03). There were no differences between apoC-III production rates of controls and those of CKD subjects. In CKD subjects, plasma apoC-III concentration was significantly and negatively correlated with apoC-III FCR (r = -0.749, P = 0.05) but not with apoC-III production rate. Plasma apoC-III concentration was positively correlated with plasma and VLDL triglycerides and VLDL apoB concentrations and negatively correlated with VLDL apoB FCR (P < 0.05 for all). ApoC-III FCR was negatively correlated with plasma and VLDL triglycerides and VLDL apoB concentration and positively correlated with VLDL apoB FCR (P < 0.05 for all). Altered plasma apoC-III metabolism is a feature of dyslipidemia in moderate CKD. Modification of apoC-III catabolism may be an important therapeutic target for reducing cardiovascular disease risk in moderate CKD.
authors.affiliation: Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Esther M M
authors.initials: EM
authors.lastname: Ooi
authors.forename: Doris T
authors.initials: DT
authors.lastname: Chan
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.forename: Dick C
authors.initials: DC
authors.lastname: Chan
authors.forename: Theodore W K
authors.initials: TW
authors.lastname: Ng
authors.forename: Gursharan K
authors.initials: GK
authors.lastname: Dogra
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Irish
authors.forename: P Hugh R
authors.initials: PH
authors.lastname: Barrett
mesh_terms: D053305:Apolipoprotein C-III / Q000097:blood* / Q000378:metabolism; D001055:Apolipoproteins B / Q000097:blood; D016022:Case-Control Studies; D015243:Cholesterol, VLDL / Q000097:blood; D002908:Chronic Disease; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007674:Kidney Diseases / Q000097:blood*; D007930:Leucine / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
chemical_list: D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D015243:Cholesterol, VLDL; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D007930:Leucine