title: Metabonomic analysis of serum metabolites in kidney transplant recipients with cyclosporine A- or tacrolimus-based immunosuppression.
abstract: BACKGROUND
  Cyclosporine A (CsA) and tacrolimus (TAC) affect the body metabolism of renal transplant recipients differently. We applied a novel method of H-nuclear magnetic resonance-based metabonomics to integrate the serum metabolic profiles of transplant recipients with normal allograft function and identify time-dependent changes in the levels of serum metabolites in response to CsA- or TAC-based immunosuppression after kidney transplantation (KT).
  
  
  METHODS
  Fifty-seven consecutive renal transplant recipients were treated with CsA-based (CsA, mycophenolate mofetil, and steroid, n=27) or TAC-based (TAC, mycophenolate mofetil, and steroid, n=30) regimens. Serum samples were analyzed at baseline (pretransplant) and 1, 3, and 6 months after KT.
  
  
  RESULTS
  The Partial Least Squares-Discriminant Analysis score plots showed a clear separation between levels at baseline and at 1, 3, and 6 months after KT in both groups. The levels of lipid metabolites were increased after KT in both groups, and importantly, CsA group demonstrated higher levels than TAC group. The metabolites for which the levels differed between the CsA and TAC groups and that changed according to treatment duration were glucose, hypoxanthine, lactate, succinate, and taurine. In contrast, trimethylamine-N-oxide levels, known to be associated with graft dysfunction, did not differ between the two groups.
  
  
  CONCLUSIONS
  These data indicate that CsA- and TAC-based immunosuppressions elicit unique changes in serum metabolic profiles after KT. H-nuclear magnetic resonance-based metabonomics could provide new insights regarding the side effects of immunosuppressive regimens.
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Chan-Duck
authors.initials: CD
authors.lastname: Kim
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Hanna
authors.initials: H
authors.lastname: Yoo
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Do Hyun
authors.initials: DH
authors.lastname: Ryu
authors.forename: Dong Woo
authors.initials: DW
authors.lastname: Noh
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Park
authors.forename: Yong-Lim
authors.initials: YL
authors.lastname: Kim
authors.forename: Geum-Sook
authors.initials: GS
authors.lastname: Hwang
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kwon
mesh_terms: D000704:Analysis of Variance; D016572:Cyclosporine / Q000627:therapeutic use*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D016030:Kidney Transplantation; D016018:Least-Squares Analysis; D008055:Lipids / Q000097:blood; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D008055:Lipids; D016572:Cyclosporine; D016559:Tacrolimus