title: NMR spectroscopy as a novel approach to the monitoring of renal transplant function.
abstract: High field 1H NMR spectroscopy was used for the rapid multicomponent analysis of low molecular wt compounds in urine in order to investigate the patterns of metabolic changes associated with early renal allograft dysfunction. Urine samples were collected daily for 14 days from 33 patients who underwent primary renal allograft transplantation, and analyzed by 500 and/or 600 MHz 1H NMR spectroscopy. All patients received 20 mg prednisolone and 5 mg/kg b.d. oral cyclosporin A (CsA) solution. In this study no patient showed clinical or histopathological evidence of CsA nephrotoxicity. For each patient the NMR-generated metabolite data were correlated with the clinical observations, graft biopsy pathology, and data from conventional laboratory techniques for assessing renal function. The NMR spectra of urine from patients with immediate functioning grafts were similar with respect to their patterns of amino acids, organic acids and organic amines, whereas the patients with delayed or non-functioning grafts showed significantly different metabolite excretion patterns. In longitudinal studies on individual patients there were increased urinary levels of trimethylamine-N-oxide (TMAO), dimethylamine (DMA), lactate, acetate, succinate, glycine and alanine during episodes of graft dysfunction. However, only the urinary concentration of TMAO was statistically significantly higher (P < 0.025) in the urine collected from patients during episodes of graft dysfunction (410 +/- 102 microM TMAO/mM creatinine) than in patients with good graft function (91 +/- 18 microM TMAO/mM creatinine) or healthy control subjects (100 +/- 50 microM TMAO/mM creatinine). These findings suggest that graft dysfunction is associated with damage to the renal medulla which causes the release of TMAO into the urine from the damaged renal medullary cells. This provides a possible novel urinary marker for post-transplant graft dysfunction. This study shows that NMR spectroscopy of biofluids, when used in combination with conventional laboratory techniques, is a valuable aid to renal transplant monitoring.
authors.affiliation: Department of Chemistry, Birkbeck College, University of London, United Kingdom.
authors.forename: P J
authors.initials: PJ
authors.lastname: Foxall
authors.forename: G J
authors.initials: GJ
authors.lastname: Mellotte
authors.forename: M R
authors.initials: MR
authors.lastname: Bending
authors.forename: J C
authors.initials: JC
authors.lastname: Lindon
authors.forename: J K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000652:urine; D004123:Dimethylamines / Q000652:urine; D005260:Female; D006085:Graft Survival; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008744:Methylamines / Q000652:urine; D008875:Middle Aged; D013997:Time Factors; D014556:Urine / Q000737:chemistry*
chemical_list: D004123:Dimethylamines; D008744:Methylamines; D016572:Cyclosporine; C034516:dimethylamine; C005855:trimethyloxamine