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Journal of Lipid Research, Vol. 50, 2524-2531, December 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

Chronic kidney disease delays VLDL-apoB-100 particle catabolism: potential role of apolipoprotein C-III

Doris T. Chan^*,, Gursharan K. Dogra, Ashley B. Irish, Esther M. Ooi^*, P. Hugh Barrett^*, Dick C. Chan^* and Gerald F. Watts^1,*

^* School of Medicine Pharmacology, Royal Perth Hospital Unit, University of Western Australia, WA, Australia
Department of Renal Medicine, Sir Charles Gairdner Hospital, WA, Australia
Department of Nephrology, Royal Perth Hospital, WA, Australia

¹ To whom correspondence should be addressed. e-mail: gwatts{at}meddent.uwa.edu.au

To determine the relative contribution of obesity and/or insulin resistance (IR) in the development of dyslipidemia in chronic kidney disease (CKD), we investigated the transport of apolipoprotein (apo) B-100 in nonobese, nondiabetic, nonnephrotic CKD subjects and healthy controls (HC). We determined total VLDL, VLDL₁, VLDL₂, intermediate density lipoprotein (IDL), and LDL-apoB-100 using intravenous D3-leucine, GC-MS, and multicompartmental modeling. Plasma apoC-III and apoB-48 were immunoassayed. In this case control study, we report higher plasma triglyceride, IDL-, VLDL-, VLDL₁-, and VLDL₂-apoB-100 concentrations in CKD compared with HC (P < 0.05). This was associated with decreased fractional catabolic rates [FCRs (pools/day)] [IDL:CKD 3.4 (1.6) vs. HC 5.0 (3.2), P < 0.0001; VLDL:CKD 4.8 (5.2) vs. HC 7.8 (4.8), P = 0.038; VLDL₁:CKD 10.1 (8.5) vs. HC 29.5 (45.1), P = 0.007; VLDL₂:CKD 5.4 (4.6) vs. HC 10.4 (3.4), P = 0.001] with no difference in production rates. Plasma apoC-III and apoB-48 were significantly higher in CKD (P < 0.001) and both correlated with impaired FCRs of VLDL, VLDL₁, and VLDL₂ apoB-100 (P < 0.05). In CKD, apoC-III concentration was the only independent predictor of clearance defects in VLDL and its subfractions. Moderate CKD in the absence of central adiposity and IR is associated with mild hypertriglyceridemia due to delayed catabolism of triglyceride rich lipoproteins, IDL, and VLDL, without changes in production rate. Altered apoC-III metabolism may contribute to dyslipidemia in CKD, and this requires further investigation.

Supplementary key words lipids • kinetic analysis • insulin resistance • central adiposity

Abbreviations: apo, apolipoprotein; BMI, body mass index; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; FCR, fractional catabolic rate; IDL, intermediate density lipoprotein; IQR, interquartile range; IR, insulin resistance; sCr, serum creatinine; TRL, triglyceride-rich lipoprotein

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