薬理と治療

Abstract

Background　Chronic kidney disease（CKD）is highly prevalent in hyperuricemic patients. Cardiovascular events╱kidney failure are more frequent in CKD patients than in patients without albuminuria. Topiroxostat, a selective xanthine oxidase inhibitor, has been reported to reduce the serum urate level and urinary albumin╱creatinine ratio（ACR）in Japanese hyperuricemic patients with stage 3 CKD. We further assessed the effect of topiroxostat on the serum urate and albuminuria. Methods　This is a post-hoc, sub-group analysis of data obtained from the previously reported multicenter, randomized, placebo-controlled, double-blind, parallel-group, 22-week study comparing the efficacy and safety of topiroxostat versus placebo in Japanese hyperuricemic stage 3 CKD patients with or without gout. We conducted sub-group analyses of the effects of topiroxostat on the serum urate, ACR, estimated glomerular filtration rate and blood pressure. Results　Both in patients receiving╱not receiving renin-angiotensin-aldosterone（RAA）inhibitors╱lipid-lowering drugs, the serum urate level decreased more in the topiroxostat group than in the placebo group. The percent change of the ACR was also significantly lower in the topiroxostat group than in the placebo group in patients receiving RAA inhibitors╱lipid-lowering drugs. In the subgroup analysis of patients with nephrosclerosis, the percent change of the ACR was significantly lower in the topiroxostat group than in the placebo group. Also in the patients with diabetic nephropathy, the percent change of the ACR tended to be lower in the topiroxostat group than in the placebo group（P＝0.059 vs. placebo）. Conclusion　The efficacy of topiroxostat in reducing the serum urate and ACR was maintained when it was administered concomitantly with RAA-blocking agents╱lipid-lowering agents.