Therapeutic Effects of Dotinurad and Febuxostat in Chronic Kidney Disease Patients with Hyperuricemia

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  • 高尿酸血症を呈する慢性腎臓病患者におけるドチヌラドとフェブキソスタットによる治療効果の比較

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Abstract

Patients with chronic kidney disease（CKD）are at high risk for developing cardiovascular diseases and hyperuricemia is associated with the progression of renal dysfunction and the incidence of cardiovascular events. In this study, we compared the effects of dotinurad（DTN）, a novel selective urate reabsorption inhibitor, and febuxostat（FBX）, a non-purine xanthine oxidase inhibitor, on cardiovascular risk profile in CKD patients. Nineteen CKD patients were given DTN （0.5, 1, 2 mg/day） or FBX （10, 20, 40 mg/day） for 3-6 months in a random crossover manner, and the indices of cardiovascular risk were evaluated at the end of each treatment period. Hypouricemic effect was not significantly different between DTN and FBX （5.5 vs 5.1 mg/dL） even in subgroup subjects with glomerular filtration rate （eGFR）＜45 mL/min/1.73 m2（5.5 vs 4.9 mg/dL）There were no significant differences in blood pressure, hemoglobin A1c and serum lipids. Indices Indices of renal injury such as eGFR （51.9 vs 50.8 mL/min/ 1.73 m 2） and albuminuria （219 vs 179 mg/gCr） did not significantly differ between DTN and FBX. Significant differences were not observed in circulating markers of oxidative stress （oxidized LDL 94 vs 102 U/L, reactive oxygen metabolites 339 vs 354 U.CARR）or inflammation （high-sensitivity CRP 1.60 vs 1.41 mg/L）. Plasma brain natriuretic peptide did not show a significant difference between the two treatment periods （48 vs 55 pg/mL）. It is suggested that DTN has comparable hypouricemic effect to xanthine oxidase inhibitors even in stage G3b CKD patients and the effects on cardiovascular risk profile is also comparable to xanthine oxidase inhibitors.

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