Kubal Dr., Chandrashekhar (2012). Comparative models of transplant and non-transplant human kidney disease. University of Birmingham. Ph.D.
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Kubal_12_PhD.pdf
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Abstract
Late kidney transplant losses along with chronic kidney disease in non-renal solid organ transplantation pose major problem in this field. To address this I compared ischaemia, interstitial scarring and inflammation on the renal biopsies from failing renal transplants and chronic kidney disease outside renal transplantation using native CKD as a control group. For matched renal function, a similar degree of interstitial scarring was observed across the three study groups. Ischaemia was predominant in failing renal transplants; conversely inflammation was predominant in native CKD. The relationship between macrophages and endothelial cells indicated that, despite a lower macrophage load, there may be an allogeneic impact of macrophages on endothelial cells. In the biopsies from CKD, mRNA levels for iNOS, arginase, CX3CL1, BCL-2, MCP-1/CCL2 and FSP-1 were increased in association with an increasing macrophage load. Macrophage load correlated positively with arginase/iNOS mRNA ratio, suggesting M2 phenotypic transformation of the macrophages. Co-localization studies, demonstrated an increased number of macrophages within 5 microns from endothelial cells in failing renal transplants when compared to chronic kidney disease. Further studies directed towards manipulating macrophage-endothelial cell interaction may be potentially beneficial in improving the longevity of renal transplants.
Type of Work: | Thesis (Doctorates > Ph.D.) |
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Award Type: | Doctorates > Ph.D. |
Licence: | |
College/Faculty: | Colleges (2008 onwards) > College of Medical & Dental Sciences |
School or Department: | School of Clinical and Experimental Medicine |
Funders: | None/not applicable |
Subjects: | R Medicine > R Medicine (General) |
URI: | http://etheses.bham.ac.uk/id/eprint/3827 |
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