Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease

abstract

This study compared the molecular lipidomic profile of LDL in patients with nondiabetic advanced renal disease and no evidence of CVD to that of age-matched controls, with the hypothesis that it would reveal proatherogenic lipid alterations. LDL was isolated from 10 normocholesterolemic patients with stage 4/5 renal disease and 10 controls, and lipids were analyzed by accurate mass LC/MS. Top-down lipidomics analysis and manual examination of the data identified 352 lipid species, and automated comparative analysis demonstrated alterations in lipid profile in disease. The total lipid and cholesterol content was unchanged, but levels of triacylglycerides and N-acyltaurines were significantly increased, while phosphatidylcholines, plasmenyl ethanolamines, sulfatides, ceramides, and cholesterol sulfate were significantly decreased in chronic kidney disease (CKD) patients. Chemometric analysis of individual lipid species showed very good discrimination of control and disease sample despite the small cohorts and identified individual unsaturated phospholipids and triglycerides mainly responsible for the discrimination. These findings illustrate the point that although the clinical biochemistry parameters may not appear abnormal, there may be important underlying lipidomic changes that contribute to disease pathology. The lipidomic profile of CKD LDL offers potential for new biomarkers and novel insights into lipid metabolism and cardiovascular risk in this disease.

keywords

PERFORMANCE LIQUID-CHROMATOGRAPHY; STAGE RENAL-FAILURE; CARDIOVASCULAR-DISEASE; MASS-SPECTROMETRY; PLASMA-LIPOPROTEINS; HUMAN LDL; RISK; ABNORMALITIES; TOOL; DISCRIMINATION

subject category

Biochemistry & Molecular Biology

authors

Reis, A; Rudnitskaya, A; Chariyavilaskul, P; Dhaun, N; Melville, V; Goddard, J; Webb, DJ; Pitt, AR; Spickett, CM

our authors

Groups

acknowledgements

This work was supported by a Marie Curie Intra-European Fellowship within the 7th European Community Framework Program (IEF 255076). A. Rudnitskaya was supported by the Portuguese Science and Technology Foundation, through the European Social Fund (ESF) and

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