Chronic kidney disease (CKD) is characterized by the progressive loss of functional nephrons. Although cardiovascular disease (CVD) complications and atherosclerosis are the leading causes of morbidity and mortality in CKD, the mechanism by which the progression of CVD accelerates remains unclear. To reveal the molecular mechanisms associated with atherosclerosis linked to CKD, we applied a shotgun lipidomics approach fortified with standard laboratory analytical methods and gas chromatography-mass spectrometry technique on selected lipid components and precursors to analyze the plasma lipidome in CKD and classical CVD patients. The MS-based lipidome profiling revealed the upregulation of triacylglycerols in CKD and downregulation of cholesterol/cholesteryl esters, sphingomyelins, phosphatidylcholines, phosphatidylethanolamines and ceramides as compared to CVD group and controls. We have further observed a decreased abundance of seven fatty acids in CKD with strong inter-correlation. In contrast, the level of glycerol was elevated in CKD in comparison to all analyzed groups. Our results revealed the putative existence of a functional causative link-the low cholesterol level correlated with lower estimated glomerular filtration rate and kidney dysfunction that supports the postulated "reverse epidemiology" theory and suggest that the lipidomic background of atherosclerosis-related to CKD is unique and might be associated with other cellular factors, i.e., inflammation.

Chair and Department of Medical Chemistry and Laboratory Medicine Poznan University of Medical Sciences 60 806 Poznan Poland

Department of Analytical Chemistry Faculty of Chemical Technology University of Pardubice 532 10 Pardubice Czech Republic

Department of Biomedical Proteomics Institute of Bioorganic Chemistry Polish Academy of Sciences 61 704 Poznan Poland

Department of Cardiac Surgery and Transplantology Poznan University of Medical Sciences 61 001 Poznan Poland

Department of Hypertension Angiology and Internal Disease Poznan University of Medical Sciences 61 001 Poznan Poland

Department of Molecular and Systems Biology Institute of Bioorganic Chemistry Polish Academy of Sciences 61 704 Poznan Poland

Department of Natural Products Biochemistry Institute of Bioorganic Chemistry Polish Academy of Sciences 61 704 Poznan Poland

Department of Nephrology Transplantology and Internal Medicine Poznan University of Medical Sciences 60 355 Poznan Poland

Institute of Computing Science Poznan University of Technology 60 965 Poznan Poland

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