Lines, Simon (2013) The influence of vitamin E bonded haemodialysis membranes on erythropoiesis stimulating agent requirements, oxidative stress, inflammation, haemostasis and outcomes. PhD thesis, University of Leeds.
Abstract
Introduction: Haemodialysis (HD) patients have high rates of cardiovascular (CV) disease and mortality yet the reasons for this have not been fully elucidated. High doses of erythropoiesis stimulating agents (ESAs), increases in oxidative stress and inflammation, and alterations to the fibrin clot phenotype are all possible contributors. Vitamin E (VE)- bonded dialysis membranes are purported to have favourable effects on a number of these parameters which were tested here in the setting of a randomised controlled trial.
Methods: Patients were randomised to HD with VE-bonded polysulfone membranes or non-VE-bonded equivalents and followed for 12 months. Data on anaemia parameters
were collected monthly and blood tests were performed at baseline, 6 and 12 months for the measurement of oxidative stress (oxidatively modified-low density lipoprotein,
thiobarbituric acid reactive species), inflammation (C-reactive protein, complement components C3, SC5b-9, factor D, properdin) and fibrin clot properties. Contemporaneous
data were collected on CV events and death.
Results: Of the 260 patients enrolled, 123 were randomised to dialysis with VE-bonded membranes. Analysis of the full dataset revealed no differential effects of the VEmembranes
on ESA requirements, oxidative stress, inflammation, fibrin clot structure or clinical outcomes. Key findings included a potential ESA-sparing effect of the VEmembranes in ESA resistant patients, a progressive decline in C3 levels over 12 months and associations between the levels of C3 and SC5b-9 at baseline and the subsequent risks of dying or experiencing a CV event.
Conclusions: There were no benefits in switching prevalent HD patients to dialysis with VE-bonded dialysis membranes with the exception of possible utility in ESA-resistant
patients. The novel finding suggesting a link between the complement system and poor outcomes in HD patients may provide further insights to explain the high rates of CV
disease and mortality for this patient group and merits further study.
Metadata
Supervisors: | Wright, Mark |
---|---|
ISBN: | 978-0-85731-671-4 |
Awarding institution: | University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) |
Identification Number/EthosID: | uk.bl.ethos.605293 |
Depositing User: | Repository Administrator |
Date Deposited: | 06 May 2014 09:00 |
Last Modified: | 18 Feb 2020 12:47 |
Open Archives Initiative ID (OAI ID): | oai:etheses.whiterose.ac.uk:5871 |
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