title: Marked increase in urinary excretion of apolipoproteins in children with nephrolithiasis associated with hypercalciuria.
abstract: Using a proteomic approach, we aimed to identify and compare the urinary excretion of proteins involved in lipid transport and metabolism in children with kidney stones and hypercalciuria (CAL), hypocitraturia (CIT), and normal metabolic work-up (NM), and in healthy controls (HCs). Additionally, we aimed to confirm these results using ELISA, and to examine the relationship between the urinary excretion of selected proteins with demographic, dietary, blood, and urinary parameters.
  
  
  
  Prospective, controlled, pilot study of pooled urine from CAL, CIT, and NM versus age- and gender-matched HCs, using liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. Results were confirmed by ELISA performed on individual samples.
  
  
  
  Of the 1,813 proteins identified, 230 met the above criteria. Of those, 5 proteins (apolipoprotein A-II [APOA2]; apolipoprotein A-IV [APOA4]; apolipoprotein C-III [APOA3]; fatty acid-binding protein, liver [FABPL]; fatty acid-binding protein, adipocyte [FABP4]) involved in lipid metabolism and transport were found in the CAL group, with significant differences compared with HCs. ELISA analysis indicated statistically significant differences in the urinary excretion of APOC3, APOA4, and FABPL in the CAL group compared with HCs. Twenty-four-hour urinary calcium excretion correlated significantly with concentrations of ApoC3 (r = 0.77, p < 0.001), and FABPL (r = 0.80, p = 0.005).
  
  
  
  We provide proteomic data showing increased urinary excretion of lipid metabolism/transport-related proteins in children with kidney stones and hypercalciuria. These findings suggest that abnormalities in lipid metabolism might play a role in kidney stone formation.
authors.affiliation: Department of Pediatric Urology, Children's Hospital of Michigan, Detroit, MI, USA. lkovacev@dmc.org.
authors.forename: Larisa
authors.initials: L
authors.lastname: Kovacevic
authors.affiliation: Department of Pediatric Urology, Children's Hospital of Michigan, Detroit, MI, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Caruso
authors.affiliation: Department of Pediatric Urology, Children's Hospital of Michigan, Detroit, MI, USA.
authors.forename: Tuhina
authors.initials: T
authors.lastname: Govil-Dalela
authors.affiliation: Department of Statistics, Children's Hospital of Michigan, Detroit, MI, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Thomas
authors.affiliation: Department of Pediatric Urology, Children's Hospital of Michigan, Detroit, MI, USA.
authors.forename: Yegappan
authors.initials: Y
authors.lastname: Lakshmanan
mesh_terms: D000293:Adolescent; D001053:Apolipoproteins / Q000378:metabolism / Q000652:urine*; D002118:Calcium / Q000378:metabolism / Q000652:urine; D002648:Child; D002853:Chromatography, Liquid; D002951:Citrates / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D053565:Hypercalciuria / Q000378:metabolism / Q000652:urine*; D007669:Kidney Calculi / Q000378:metabolism / Q000652:urine*; D008297:Male; D013058:Mass Spectrometry; D010865:Pilot Projects; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods; D065667:Renal Elimination
chemical_list: D001053:Apolipoproteins; D002951:Citrates; D050556:Fatty Acid-Binding Proteins; D002118:Calcium
keywords: Children; Hypercalciuria; Nephrolithiasis; Proteomics; Urinary apolipoproteins