title: Muscle metabolites, detected in urine by proton spectroscopy, correlate with disease damage in juvenile idiopathic inflammatory myopathies.
abstract: OBJECTIVE
  To assess for novel markers of muscle damage using urinary muscle metabolites by 1H magnetic resonance spectroscopy in patients with juvenile idiopathic inflammatory myopathy (IIM).
  
  
  METHODS
  Creatine (Cr), choline (Cho), betaine (Bet), glycine (Gly), trimethylamine oxide (TMAO), and several other metabolites were measured in first morning void urine samples from 45 patients with juvenile IIM and from 35 healthy age-matched controls, and correlated with measures of myositis disease activity and damage. Urinary metabolite to age-adjusted creatinine (Cn) ratios were examined.
  
  
  RESULTS
  Age-adjusted initial Cr:Cn, Cho:Cn, Bet:Cn, Gly:Cn, and TMAO:Cn ratios were higher in patients with juvenile IIM than controls (P < 0.01). Cr:Cn ratios showed significant correlations with physician-assessed global disease damage (Spearman rs = 0.37; P = 0.01), Steinbrocker functional class (rs = 0.35; P = 0.02), serum Cr (rs = 0.72; P = 0.001), and lactate dehydrogenase (rs = 0.34; P = 0.03) levels. Cho:Cn (rs = 0.3; P = 0.05), Gly:Cn (rs = 0.33; P = 0.03), and TMAO:Cn (rs = 0.36; P = 0.02) ratios showed a significant correlation with serum aldolase levels. Cho:Cn ratios also showed a significant correlation with aspartate aminotransferase levels (rs = 0.35; P = 0.02). A linear regression model was used to evaluate the factors influencing urinary Cr:Cn ratios in the 43 patients with data sets available at the initial visit. The regression model explained 73% of the variation in Cr:Cn ratios. The most significant factor was the physician-assessed global disease damage (R2 = 0.50, P = 0.015).
  
  
  CONCLUSIONS
  Urinary Cr:Cn, Cho:Cn, Bet:Cn, Gly:Cn, and TMAO:Cn ratios are elevated in juvenile IIM and Cr:Cn correlates strongly with global disease damage. The Cr:Cn ratio may have potential utility as a marker of myositis disease damage.
authors.affiliation: GKT School of Medicine, Imperial College School of Medicine, Hammersmith Hospital Campus, London, United Kingdom. ychung@sghms.ac.uk
authors.forename: Y-L
authors.initials: YL
authors.lastname: Chung
authors.forename: L G
authors.initials: LG
authors.lastname: Rider
authors.forename: J D
authors.initials: JD
authors.lastname: Bell
authors.forename: R M
authors.initials: RM
authors.lastname: Summers
authors.forename: L S
authors.initials: LS
authors.lastname: Zemel
authors.forename: R M
authors.initials: RM
authors.lastname: Rennebohm
authors.forename: M H
authors.initials: MH
authors.lastname: Passo
authors.forename: J
authors.initials: J
authors.lastname: Hicks
authors.forename: F W
authors.initials: FW
authors.lastname: Miller
authors.forename: D L
authors.initials: DL
authors.lastname: Scott
mesh_terms: D000293:Adolescent; D001622:Betaine / Q000652:urine; D015415:Biomarkers / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D002794:Choline / Q000652:urine; D003401:Creatine / Q000652:urine; D005260:Female; D005998:Glycine / Q000652:urine; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008744:Methylamines / Q000652:urine; D009132:Muscles / Q000378:metabolism*; D009220:Myositis / Q000652:urine*
chemical_list: D015415:Biomarkers; D008744:Methylamines; D001622:Betaine; C005855:trimethyloxamine; D003401:Creatine; D002794:Choline; D005998:Glycine