title: Systematic variations associated with renal disease uncovered by parallel metabolomics of urine and serum.
abstract: BACKGROUND
  Membranous nephropathy is an important glomerular disease characterized by podocyte injury and proteinuria, but no metabolomics research was reported as yet. Here, we performed a parallel metabolomics study, based on human urine and serum, to comprehensively profile systematic metabolic variations, identify differential metabolites, and understand the pathogenic mechanism of membranous nephropathy.
  
  
  RESULTS
  There were obvious metabolic distinctions between the membranous nephropathy patients with urine protein lower than 3.5 g/24 h (LUPM) and those higher than 3.5 g/24 h (HUPM) by Partial Least Squares Discriminant Analysis (PLS-DA) model analysis. In total, 26 urine metabolites and 9 serum metabolites were identified to account for such differences, and the majority of metabolites were significantly increased in HUPM patients for both urines and serums. Combining the results of urine with serum, all differential metabolites were classified to 5 classes. This classification helps globally probe the systematic metabolic alterations before and after blood flowing through kidney. Citric acid and 4 amino acids were markedly increased only in the serum samples of HUPM patients, implying more impaired filtration function of kidneys of HUPM patients than LUPM patients. The dicarboxylic acids, phenolic acids, and cholesterol were significantly elevated only in urines of HUPM patients, suggesting more severe oxidative attacks than LUPM patients.
  
  
  CONCLUSIONS
  Parallel metabolomics of urine and serum revealed the systematic metabolic variations associated with LUPM and HUPM patients, where HUPM patients suffered more severe injury of kidney function and oxidative stresses than LUPM patients. This research exhibited a promising application of parallel metabolomics in renal diseases.
authors.affiliation: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, China.
authors.forename: Xianfu
authors.initials: X
authors.lastname: Gao
authors.forename: Wanjia
authors.initials: W
authors.lastname: Chen
authors.forename: Rongxia
authors.initials: R
authors.lastname: Li
authors.forename: Minfeng
authors.initials: M
authors.lastname: Wang
authors.forename: Chunlei
authors.initials: C
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.forename: Yueyi
authors.initials: Y
authors.lastname: Deng
mesh_terms: D001774:Blood Chemical Analysis; D008401:Gas Chromatography-Mass Spectrometry; D015433:Glomerulonephritis, Membranous / Q000097:blood* / Q000378:metabolism / Q000473:pathology / Q000652:urine*; D006801:Humans; D055432:Metabolomics / Q000379:methods*; D049490:Systems Biology / Q000379:methods*; D016482:Urinalysis