title: Combined Clinical Phenotype and Lipidomic Analysis Reveals the Impact of Chronic Kidney Disease on Lipid Metabolism.
abstract: Chronic kidney disease (CKD) results in significant dyslipidemia and profound changes in lipid and lipoprotein metabolism. The associated dyslipidemia, in turn, contributes to progression of CKD and its cardiovascular complications. To gain an in-depth insight into the disorders of lipid metabolism in advanced CKD, we applied UPLC-HDMS-based lipidomics to measure serum lipid metabolites in 180 patients with advanced CKD and 120 age-matched healthy controls. We found significant increases in the levels of total free fatty acids, glycerolipids, and glycerophospholipids in patients with CKD. The levels of free fatty acids, glycerolipids, and glycerophospholipids directly correlated with the level of serum triglyceride and inversely correlated with the levels of total cholesterol and eGFR. A total of 126 lipid species were identified from positive and negative ion modes. Out of 126, 113 identified lipid species were significantly altered in patients with CKD based on the adjusted FDR method. These results pointed to profound disturbance of fatty acid and triglyceride metabolisms in patients with CKD. Logistic regression analysis showed strong correlations between serum methyl hexadecanoic acid, LPC(24:1), 3-oxooctadecanoic acid, and PC(20:2/24:1) levels with eGFR and serum creatinine levels (R > 0.8758). In conclusion, application of UPLC-HDMS-based lipidomic technique revealed profound changes in lipid metabolites in patients with CKD. The observed increases in serum total fatty acids, glycerolipids, and glycerophospholipids levels directly correlated with increased serum triglyceride level and inversely correlated with the eGFR and triglyceride levels.
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University , No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University , No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University , No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University , No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China.
authors.forename: Dan-Qian
authors.initials: DQ
authors.lastname: Chen
authors.affiliation: Division of Nephrology and Hypertension, School of Medicine, University of California Irvine , MedSci 1 C352, Irvine, California 92897, United States.
authors.forename: Nosratola D
authors.initials: ND
authors.lastname: Vaziri
authors.affiliation: Department of Nephrology, Affiliated Hospital of Shaanxi Institute of Traditional Chinese Medicine , No. 2 Xihuamen, Xi'an, Shaanxi 710003, China.
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Yu
authors.affiliation: Department of Nephrology, Xi'an No. 4 Hospital , No. 2 Jiefang Road, Xi'an, Shaanxi 710004, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Baoji Central Hospital , No. 8 Jiangtan Road, Baoji, Shaanxi 721008, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Su
authors.affiliation: Solution Centre, Waters Technologies (Shanghai) Ltd. , No. 1000 Jinhai Road, Shanghai 201203, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Bai
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University , No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China.
authors.forename: Ying-Yong
authors.identifier: 0000-0002-0239-7342
authors.initials: YY
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D002784:Cholesterol / Q000097:blood; D050171:Dyslipidemias / Q000097:blood* / Q000235:genetics / Q000473:pathology; D005227:Fatty Acids / Q000097:blood; D005260:Female; D020404:Glycerophospholipids / Q000097:blood; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000235:genetics / Q000473:pathology; D014280:Triglycerides / Q000097:blood*
chemical_list: D005227:Fatty Acids; D020404:Glycerophospholipids; D008055:Lipids; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol
keywords: chronic kidney disease; fatty acid metabolism; glomerular filtration rate; lipid metabolism; lipidomics; triglyceride metabolism