title: H-NMR-based metabolic signatures of mild and severe ischemia/reperfusion injury in rat kidney transplants.
abstract: BACKGROUND
  Severe ischemia/reperfusion (IR) injury is a risk factor for delayed graft function. Delayed graft function remains difficult to predict, and it currently relies primarily on serum creatinine (SCr), urine output, and occasionally on graft biopsy. (1)H-NMR (nuclear magnetic resonance spectroscopy) based metabolomics was used to establish IR-specific metabolic markers in both blood and kidney tissue. These markers were compared to SCr and graft histology.
  
  
  METHODS
  Male Lewis rats were used for kidney transplantation. Two cold ischemia (CI) groups (24- and 42-hour) and two transplantation groups [after 24 (TX24) and after 42 hours (TX42) of CI] were compared to a control group. Whole blood and kidney tissue were collected for further analysis.
  
  
  RESULTS
  SCr levels taken 24 hours after transplantation were 1.6 +/- 0.12 mg/dL (TX24) and 2.1 +/- 0.5 mg/dL (TX42), (P= n.s.). Histology samples revealed mild injury in the TX24 group and severe injury in the TX42 group. A significantly decreased level of polyunsaturated fatty acids (PUFA) and elevated levels of allantoin, a marker of oxidative stress, was found in the renal tissue. In the blood, both trimethylamine-N-oxide (TMAO), a marker of renal medullary injury, and allantoin were significantly increased. Allantoin levels were low in both the control and CI groups. Levels were significantly increased after reperfusion (control 0.02 +/- 0.03 micromol/mL, TX24 1.13 +/- 0.22, and TX42 1.89 +/- 0.38, P < 0.001), and correlated with cold ischemia time (r= 0.96) and TMAO (r= 0.94).
  
  
  CONCLUSIONS
  The (1)H-NMR metabolic profiles of both the mild and severe IR groups revealed significant changes consistent with graft histology, while the SCr did not.
authors.affiliation: Department of Anesthesiology, Biomedical MRI/MRS, University of Colorado Health Sciences Center, Denver, Colorado, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Serkova
authors.forename: T Florian
authors.initials: TF
authors.lastname: Fuller
authors.forename: Jost
authors.initials: J
authors.lastname: Klawitter
authors.forename: Chris E
authors.initials: CE
authors.lastname: Freise
authors.forename: Claus U
authors.initials: CU
authors.lastname: Niemann
mesh_terms: D000481:Allantoin / Q000378:metabolism; D000818:Animals; D003404:Creatinine / Q000097:blood; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008744:Methylamines / Q000097:blood; D051381:Rats; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000378:metabolism*; D014527:Uric Acid / Q000097:blood
chemical_list: D005231:Fatty Acids, Unsaturated; D008744:Methylamines; D017382:Reactive Oxygen Species; D014527:Uric Acid; D000481:Allantoin; D003404:Creatinine; C005855:trimethyloxamine