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<https://discovery.ucl.ac.uk/id/eprint/10168499> <http://purl.org/ontology/bibo/abstract> "This project examines the pathogenic processes that lead to kidney disease in scleroderma and tests a novel therapy for scleroderma kidney disease in a clinical trial. I describe three programmes of experiment to identify possible pathogenic targets and new treatment strategies in scleroderma kidney disease.\r\nThe first divides a large cohort of patients according to their immunological and renal phenotypes, uses genome wide association to identify possible risk genes and then interrogates candidate genes further by staining renal disease tissue for the relevant gene products.\r\nIn the second stream of investigation, I describe a project to develop novel biomarkers of renal disease activity by measuring concentrations of candidate proteins in urine and serum of scleroderma patients and compare the measurements from matched control groups.\r\nThe final set of investigations is a randomised control clinical trial, testing the safety and efficacy of the highly selective endothelin antagonist zibotentan in renal outcomes for patients with scleroderma-associated chronic kidney disease and scleroderma renal crisis. Outcomes are assessed by traditional clinical measures of renal function as well as deploying novel disease activity biomarkers developed in parallel in my earlier experiments. In a parallel study I assess the pharmacokinetics of zibotentan in patients on haemodialysis."^^<http://www.w3.org/2001/XMLSchema#string> .
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