Allopurinol benefits left ventricular mass and endothelial dysfunction in chronic kidney disease

Abstract

Allopurinol ameliorates endothelial dysfunction and arterial stiffness among patients without chronic kidney disease (CKD), but it is unknown if it has similar effects among patients with CKD. Furthermore, because arterial stiffness increases left ventricular afterload, any allopurinol-induced improvement in arterial compliance might also regress left ventricular hypertrophy (LVH). We conducted a randomized, double-blind, placebo-controlled, parallel-group study in patients with stage 3 CKD and LVH. We randomly assigned 67 subjects to allopurinol at 300 mg/d or placebo for 9 months; 53 patients completed the study. We measured left ventricular mass index (LVMI) with cardiac magnetic resonance imaging (MRI), assessed endothelial function by flow-mediated dilation (FMD) of the brachial artery, and evaluated central arterial stiffness by pulse-wave analysis. Allopurinol significantly reduced LVH (P=0.036), improved endothelial function (P=0.009), and improved the central augmentation index (P=0.015). This study demonstrates that allopurinol can regress left ventricular mass and improve endothelial function among patients with CKD. Because LVH and endothelial dysfunction associate with prognosis, these results call for further trials to examine whether allopurinol reduces cardiovascular events in patients with CKD and LVH.

Figure 1.

Consort diagram of study, with a total of 67 patients randomized, but after 14 withdrawals, only 53 patients completed the study and had their data analyzed.

Figure 2.

Significant regression of LVMI in the allopurinol group compared to the placebo group after 9 months, as measured by cardiac MRI.

Figure 3.

Significant improvement seen in FMD in the allopurinol group (especially after 9 months), compared to placebo. Data is mean ± SEM.

Figure 4.

Significant improvement seen in AIx in the allopurinol group (especially after 9 months), compared to placebo. Data is mean ± SEM.