Plasma apolipoprotein C-III metabolism in patients with chronic kidney disease

• Published in: Journal of lipid research 2011-04, Vol.52 (4), p.794-800
• Main Authors: Ooi, Esther M.M., Chan, Doris T., Watts, Gerald F., Chan, Dick C., Ng, Theodore W.K., Dogra, Gursharan K., Irish, Ashley B., Barrett, P. Hugh R.
• Format: Article
• Language: English
• Subjects: Apolipoprotein C-III - blood; Apolipoprotein C-III - metabolism; Apolipoproteins B - blood; Case-Control Studies; Cholesterol, VLDL - blood; Chronic Disease; Female; Gas Chromatography-Mass Spectrometry; Humans; Kidney Diseases - blood; kinetics; Leucine - blood; lipoprotein metabolism; Lipoproteins, HDL - blood; Lipoproteins, VLDL - blood; Male; Middle Aged; Patient-Oriented and Epidemiological Research; triglycerides; Triglycerides - blood
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M011163

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.