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Title: Modulation of phosphate in dialysis patients and in normal individuals has an impact on FGF23, tissue phosphate and markers of bone turnover
Author: Bhargava, Ramya
ISNI:       0000 0005 0289 6653
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2018
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Background: Hyperphosphataemia in dialysis patients presents a therapeutic challenge. A high concentration of serum phosphate is statistically associated with increased all-cause mortality and cardiovascular events in observational studies. This association has resulted in the development of targets for control of serum phosphate and development of expensive phosphate binder tablets, to which non-adherence is common. There is an urgent need for prospective trial data to determine whether treatment with oral phosphate binders results in improved clinical outcomes, and if so, what the treatment target concentration should be. In this thesis, I examine various aspects of disordered phosphate metabolism and the feasibility of undertaking a multi-centre trial to determine the importance of serum phosphate control in dialysis patients. The thesis is presented in the publication-format, where each chapter addresses a different aspect of phosphate metabolism, and is presented as separate but related research questions. Methodology: To determine feasibility, I designed and executed a dual centre interventional trial of 104 dialysis patients, randomized to two groups (higher range and lower range groups) with different treatment targets for serum phosphate concentration. A titration phase of 2 months was followed by a maintenance phase of 10 months. Data collected included recruitment rate, drop-out rate, mortality, separation of serum phosphate concentration between the two groups and the possibility of maintaining a significant separation between the groups for the duration of the study. Symptom scores and FGF23 levels were examined. I also undertook a small study of dialysis patients with known vascular calcification and examined them for the presence of retinal vessel calcification by detailed fundoscopic testing, and increased calcium/phosphate deposition in their skin from biopsies. Results: 104 participants were recruited and randomised, from a pool of 768 screened dialysis patients (13.5%). 66 patients completed the full 12 month follow up. Statistical analysis was limited by the small number of participants, and therefore descriptive statistics are presented in the majority of cases. Median serum parathyroid hormone and FGF23 did not rise significantly in either group. There was no significant difference in symptom scores between the groups. Nine patients in the higher range group and 2 patients in the lower range group died during the study. Conclusion: It is feasible to conduct a larger multi-centre trial, randomizing dialysis patients to different treatment targets for serum phosphate, and maintaining them within a specified target range, over a period of 2 or 3 years. The sample size would depend on the event rate and specific study design - currently being debated within the UK renal community.
Supervisor: Brenchley, Paul Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: phosphate ; phosphate binders ; randomized controlled trial ; mortality ; clinical outcomes ; Dialysis