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Title: NMR-based metabolomic studies in transplantation
Author: Fenton, Hayley Michelle
ISNI:       0000 0004 2740 2923
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2011
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Acute rejection is one of the most common forms of graft damage following solid organ transplantation and recurrent episodes can have deleterious effects on long term graft survival. Episodes can vary from severe to sub-clinical and definitive diagnosis can only be carried out using an invasive biopsy, which can not only cause damage to the graft, but can allow detection of an acute rejection episode to be delayed, allowing further immunological damage to the graft. For this reason, l H-NMR spectroscopy and pattern recognition techniques were applied to sample. from those undergoing either kidney or liver transplantation in an attempt to elucidate a biornarker of acute rejection. In the case of kidney transplantation. lower level of ether phospholipids (p = 0.010). ethanolamine phospholipid (p == 0.010) and diacyl glycerophospholipids (p = 0.020 were found in the lipidic component of erythrocyte extracts from those patients undergoing an acute rejection episode compared to those who did not. Specific fatty acids were also reduced including linoleic acid (p = 0.0 I 0), arachidonic, eicosapentaenoic and related fatty acid (p = 0.0 13) and the degree of unsaturation of the fatty acid chains was reduced in rejecting patients (p = 0.038). This is indicative of increased oxidative stress in the erythrocyte of rejecting patients. The aqueous component of the erythrocytes yielded creatinine at the most influential marker, alongside ketones, organic acids amino acids and adenine nucleotide. Subsequent dynamic modeling allowed the time-dependent trends in creatinine throughout the seven day study period to be related to the transplant outcome. Analysis of both the low molecular weight and macromolecular components of the plasma of liver transplant patients did not allow identification of an acute rejection marker but did allow visualisation of the Changes occurring to the metabolic profile following transplantation. Increases in low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were observed over the seven day post-transplant. corresponding with a recovery of liver function. Increased levels of glycoprotein were also observed, which may occur as a result of a reaction to the trauma caused by surgery. A reduction in choline phospholipids was also observed, which has also been observed following major surgery. These NMR studies have provided useful insights on acute rejection and the transplant process.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available