Kidney Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Kidney Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

H-NMR-based metabolic signatures of mild and severe ischemia/reperfusion injury in rat kidney transplants.

Serkova N, Fuller TF, Klawitter J, Freise CE, Niemann CU

Department of Anesthesiology, Biomedical MRI/MRS, University of Colorado Health Sciences Center, Denver, Colorado, USA.

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). CONCLUSION: 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.

Published 8 February 2005 in Kidney Int, 67(3): 1142-51.
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