Dialysis – Transplantation
Kidney International (2005) 67, 1142–1151; doi:10.1111/j.1523-1755.2005.00181.x
1H-NMR–based metabolic signatures of mild and severe ischemia/reperfusion injury in rat kidney transplants
NATALIE SERKOVA, T FLORIAN FULLER, JOST KLAWITTER, CHRIS E FREISE and CLAUS U NIEMANN
Department of Anesthesiology, Biomedical MRI/MRS, University of Colorado Health Sciences Center, Denver, Colorado; Department of Urology, CCM Charité Universitaetsmedizin Berlin, Germany; and Division of Transplantation, Department of Surgery, and Department of Anesthesia and Perioperative Care, University of California, San Francisco, California
Correspondence: Claus U. Niemann, M.D., University of California at San Francisco, Department of Anesthesia and Perioperative Care, 521 Parnassus Avenue, C 450, San Francisco, CA 94143–0648. E-mail:niemannc@anesthesia.ucsf.edu No reprints available
Received 15 April 2004; Revised 15 July 2004; Accepted 28 September 2004.
Abstract
1H-NMR–based metabolic signatures of mild and severe ischemia/reperfusion injury in rat kidney transplants.
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. 1H-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 
mol/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 1H-NMR metabolic profiles of both the mild and severe IR groups revealed significant changes consistent with graft histology, while the SCr did not.
Keywords:
oxidative stress, allantoin, ischemia reperfusion injury
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
RESEARCH
Site-specific DNA binding using a variation of the double stranded RNA binding motif
Nature Structural Biology Letter (01 Jul 1998)
Nature Article (13 Oct 1983)
NMR spectroscopy as a novel approach to the monitoring of renal transplant function
Kidney International Original Article
Molecular Systems Biology Article (15 Jul 2008)
