The principle aim of this study was to build a national cohort of children with Steroid Resistant Nephrotic Syndrome (SRNS). The secondary aims were to establish a national registry of rare renal disease in order to build the SRNS cohort. Furthermore, to phenotype and genotype the cohort and undertake development of assays that may be effective biomarkers of disease activity peritransplantation. The successful introduction of the National Registry of Rare Renal Disease, www.renalradar.org. has enabled the nephrology community in the UK to change how it approaches patients that were otherwise considered rare, isolated and difficult to manage. Patients and their families benefit directly, not only from the research but also from the on-going education of treating clinicians and by accessing patient support through the registry. This project has produced novel work in different forms: Firstly it has built a cohort of 226 paediatric patients from around the UK with SRNS, 10% of whom have congenital nephrotic syndrome. With the collection of clinical data from a mean follow-up period of 6 years, it can be shown that in this cohort, there is a 50% risk of end stage renal failure within 10years of diagnosis. In addition, 26% of transplants were complicated by recurrence of disease. Secondly, the use of massively parallel sequencing to analyse 24 genes associated with nephrotic syndrome in 108 patients identifies a definite or probable disease causing mutation in 18.5%, including in genes that would not normally be tested in this age group. It also clearly demonstrates the need to test a panel of genes, as phenotype does not accurately predict genotype. Lastly, the identification of potential biomarkers of disease in post-transplant recurrence: Both an increase in the phosphorylation of VASP (vasodilator stimulated phosphoprotein), and an increase in motility in human podocyte cell lines occur in response to human disease plasma compared to paired remission plasma from the same patients. Identifying those patients most likely to benefit from therapy and developing effective clinical agents remain the goal in SRNS, and this work will significantly aid progress towards that end.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:686640 |
| Date | January 2014 |
| Creators | McCarthy, Hugh James |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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