Renal and Blood Pressure Effects of Xanthine Oxidase Inhibitors in the FAST trial

Abstract

This thesis reviews current evidence looking at the impact of hyperuriaemia on renal function and blood pressure and control of hyperuricaemia with xanthine oxidase inhibitors. Data from the Febuxostat versus Allopurinol Streamlined (FAST) trial is presented in three studies:1) Up-Titration of Allopurinol in Patients with Gout. Patients recruited into the FAST trial have their sUA levels measured at the screening visit and patients with sUA >357 µmol/L require up-titration of allopurinol dose to achieve EULAR recommended sUA levels prior to randomisation. The up-titration process involves increasing allopurinol dose by 100mg and re-checking sUA after 2 weeks. Dose increases of 100mg are repeated every fortnight until sUA is <357 µmol/L or the patient is taking their maximum tolerated dose of allopurinol. This analysis of FAST patients looked at the proportion of patients who required up-titration, the number of up-titrations required and any associated side effects. 2) FAST Blood Pressure Sub-Study. Home monitored blood pressure was measured in FAST patients who were recruited into a blood pressure sub-study between December 2012 and January 2014. Patients recorded home blood pressure measurements after randomisation, after optimisation of urate lowering therapy (if applicable), after a washout period and after 8 weeks of randomised treatment. Analysis was undertaken looking at changes in blood pressure between patients randomised to allopurinol and those randomised to febuxostat and changes in blood pressure in relation to changes in sUA.3) Interim Analysis of Renal Function at Annual Follow Up in FAST patients.Renal function is measured in all FAST patients with blood tests taken at screening and at every annual visit. Serum creatinine is used with screening data (age, sex, height and weight) to calculate an estimated glomerular filtration rate (eGFR) and creatinine clearance (CrCl) for every patient. The renal function interim analysis looked at data from consecutively randomised FAST patients recruited between 1st January 2012 and 31st May 2013 and assessed how changes in sUA related to changes in CrCl over 1 year.

Date of Award	2018
Original language	English
Awarding Institution	University of Dundee
Supervisor	Thomas MacDonald (Supervisor) & Isla Mackenzie (Supervisor)