Takashi Wada1, Tatsuo Hosoya2, Daisuke Honda3, Ryusuke Sakamoto4, Kazutaka Narita5, Tomomitsu Sasaki6, Daisuke Okui6, Kenjiro Kimura7. 1. Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan. 2. Department of Pathophysiology and Therapy in Chronic Kidney Disease, Jikei University School of Medicine, Tokyo, Japan. 3. Drug Development Center, Sanwa Kagaku Kenkyusho Co., Ltd., Nagoya, Aichi, Japan. d_honda@skk-net.com. 4. R&D Strategy Center, Sanwa Kagaku Kenkyusho Co., Ltd., Nagoya, Aichi, Japan. 5. Drug Development Center, Sanwa Kagaku Kenkyusho Co., Ltd., Nagoya, Aichi, Japan. 6. Medical R&D Division, Fuji Yakuhin Co., Ltd., Saitama, Japan. 7. JCHO Tokyo Takanawa Hospital, Tokyo, Japan.
Abstract
BACKGROUND: Hyperuricemia is supposed to be an independent risk factor for kidney dysfunction in diabetic patients. We attempted to examine the uric acid-lowering effect and the renoprotective effect of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia in this pilot study. METHODS: The study design was randomized, double-blind, placebo-controlled, parallel-group study. A total of 65 patients with hyperuricemia and diabetic nephropathy with microalbuminuria were enrolled and assigned to either the topiroxostat group or the placebo group. Topiroxostat (stepwise dosing from 40 to 160 mg/day) or matching placebo was administered BID for 28 weeks. The primary endpoint was a change in the urinary albumin-to-creatinine ratio in the first-morning-void urine sample. Secondary endpoints were changes in the estimated glomerular filtration rate and the serum uric acid level. RESULTS: At 28 weeks, there was no significant difference in the percent change from baseline in the urinary albumin-to-creatinine ratio between the two groups (topiroxostat: 0 vs. placebo: 17%, p = 0.3206), but the changes in the estimated glomerular filtration rate (- 0.2 vs. - 4.0 mL/min/1.73 m2, p = 0.0303) and the serum uric acid level (- 2.94 vs. - 0.20 mg/dL, p < 0.0001) were significantly different between the topiroxostat and placebo groups. Gouty arthritis occurred in 1 patient in the placebo group and no patients in the topiroxostat group. CONCLUSION: These findings support that diabetic nephropathy combined with hyperuricemia may be associated with kidney dysfunctions. Topiroxostat provides strict control of the serum uric acid level preventing decline of eGFR in these patients.
RCT Entities:
BACKGROUND:Hyperuricemia is supposed to be an independent risk factor for kidney dysfunction in diabeticpatients. We attempted to examine the uric acid-lowering effect and the renoprotective effect of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia in this pilot study. METHODS: The study design was randomized, double-blind, placebo-controlled, parallel-group study. A total of 65 patients with hyperuricemia and diabetic nephropathy with microalbuminuria were enrolled and assigned to either the topiroxostat group or the placebo group. Topiroxostat (stepwise dosing from 40 to 160 mg/day) or matching placebo was administered BID for 28 weeks. The primary endpoint was a change in the urinary albumin-to-creatinine ratio in the first-morning-void urine sample. Secondary endpoints were changes in the estimated glomerular filtration rate and the serum uric acid level. RESULTS: At 28 weeks, there was no significant difference in the percent change from baseline in the urinary albumin-to-creatinine ratio between the two groups (topiroxostat: 0 vs. placebo: 17%, p = 0.3206), but the changes in the estimated glomerular filtration rate (- 0.2 vs. - 4.0 mL/min/1.73 m2, p = 0.0303) and the serum uric acid level (- 2.94 vs. - 0.20 mg/dL, p < 0.0001) were significantly different between the topiroxostat and placebo groups. Gouty arthritis occurred in 1 patient in the placebo group and no patients in the topiroxostat group. CONCLUSION: These findings support that diabetic nephropathy combined with hyperuricemia may be associated with kidney dysfunctions. Topiroxostat provides strict control of the serum uric acid level preventing decline of eGFR in these patients.
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