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-1-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-1-nuclear magnetic resonance-based metabonomics could provide new insights regarding the side effects of immunosuppressive regimens.