eprintid: 10168499
rev_number: 12
eprint_status: archive
userid: 699
dir: disk0/10/16/84/99
datestamp: 2023-05-25 14:56:31
lastmod: 2023-05-25 14:56:31
status_changed: 2023-05-25 14:56:31
type: thesis
metadata_visibility: show
sword_depositor: 699
creators_name: Stern, Edward Phineas Stern
title: The causes and treatment of kidney disease in scleroderma
ispublished: unpub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
note: Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
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.
The 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.
In 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.
The 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.
date: 2023-04-28
date_type: published
oa_status: green
full_text_type: other
thesis_class: doctoral_open
thesis_award: Ph.D
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2017054
lyricists_name: Stern, Edward
lyricists_id: ESTER48
actors_name: Stern, Edward
actors_id: ESTER48
actors_role: owner
full_text_status: public
pagerange: 1-185
pages: 185
institution: UCL (University College London)
department: Division of Medicine
thesis_type: Doctoral
citation:        Stern, Edward Phineas Stern;      (2023)    The causes and treatment of kidney disease in scleroderma.                   Doctoral thesis  (Ph.D), UCL (University College London).     Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10168499/2/edward%20stern%20phd%20thesis%20for%20deposit%2017-4-23.pdf