Clinical Effects of Topiroxostat on Renal and Endothelial Function in A Patient with Chronic Kidney Disease and Hyperuricemic Arteriolopathy: A Case Report

Abstract

Hyperuricemia is associated with the progression of chronic kidney disease (CKD) and cardiovascular diseases. Topiroxostat, a selective xanthine oxidase inhibitor, effectively reduces serum uric acid (UA) levels and urinary albumin excretion (UAE) in CKD patients. A 50-year-old Japanese man was referred to our hospital due to albuminuria and hyperuricemia, and renal biopsy showed a typical hyperuricemic arteriolopathy. Treatment with topiroxostat decreased serum UA levels (9.2 mg/dL at baseline to 6.4 mg/dL after 6 months), UAE (388 to 88 mg/g.cr), and urinary level of liver-type fatty acid-binding protein (28.8 to 19.8 µg/g.cr). Interestingly, topiroxostat treatment was associated with a trend towards improved flow-mediated dilation (5.4 to 5.8%). These results suggested that topiroxostat in CKD patients with hyperuricemia is potentially effective, not only for ameliorating renal damages but also for improving endothelial function beyond its UA-lowering action.

The effects of xanthine oxidase inhibitor in patients with chronic heart failure complicated with hyperuricemia: a prospective randomized controlled clinical trial of topiroxostat vs allopurinol—study protocol

“…Kawamorita et al [28] demonstrated that the renoprotective effects of topiroxostat could be attributed to its potential anti-oxidative action as demonstrated by inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in concert with suppression of intracellular uric acid production. In addition, it is also suggested that topiroxostat improves vascular endothelial function [7]. Recently, Kuki et al [15] demonstrated that topiroxostat reduced not only serum uric acid level, but also urinary albumin excretion, serum hsCRP level, and plasma BNP level in patients with hyperuricemia at high risk for cardiovascular diseases.…”

“…Unlike allopurinol, topiroxostat has shown renoprotective effects as demonstrated by the reduction of urinary albumin excretion, and thus can also be used without dose reduction in patients with mild to moderate renal dysfunction [6]. In addition, it is also suggested that topiroxostat ameliorates impaired vascular endothelial function beyond the uric acid lowering action [7]. These pharmacological actions of topiroxostat lead us to the hypothesis that this drug could have superior effects to allopurinol for patients with chronic heart failure and hyperuricemia.…”