The effect of allopurinol on left ventricular mass in haemodialysis patients
Premature cardiovascular death is the leading cause of death amongst patients with end stage renal disease. Increased left ventricular mass (LVM) is strongly associated with all-cause and cardiovascular mortality. Reduction of LVM may improve outcomes. Allopurinol has reduced LVM in randomised controlled trials in chronic kidney disease, diabetes and ischaemic heart disease. The aim of this thesis was to investigate whether allopurinol might also regress left ventricular mass indexed to body surface area (LVMI) in a haemodialysis population. A multicentre double blind randomised controlled trial was performed. 80 haemodialysis patients were randomly assigned to allopurinol 300mg or placebo after each dialysis session for 1 year. LVMI was assessed by cardiac magnetic resonance imaging (CMR) performed on the post HD day at baseline and after a year of treatment. The secondary outcomes were change in blood pressure (BP), flow mediated dilation (FMD), augmentation indices (Aix) and pulse wave velocity (PWV). 53 patients completed the study and were included in the final analysis, by intention to treat. In an unadjusted analysis allopurinol did not regress LVMI - change in LVMI (g/m2): placebo +3.6 ± 10.4, allopurinol +1.6 ± 11 p=0.49. In a sub-group analysis of patients who achieved a reduction in urate of 20% or more with allopurinol, allopurinol significantly reduced LVMI- change in LVMI placebo +3.6 ± 10.4 versus -2.9 ± 7 p= 0.03. Allopurinol had no demonstrable effect on BP, FMD, Aix or PWV. This thesis shows that, compared with placebo, treatment with allopurinol did not regress LVMI in haemodialysis patients. However, in those patients on allopurinol who achieved a 20% reduction in urate there was a significant reduction in LVMI suggesting effect of allopurinol on LVMI is dependent on effective dose. A larger scale trial to see if allopurinol reduces CV outcomes in HD patients is warranted, with a target reduction of at least 20% in urate in the active arm.
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