Uric acid-lowering and renoprotective effects of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia: a randomized, double-blind, placebo-controlled, parallel-group study (UPWARD study)

Takashi Wada, Tatsuo Hosoya, Daisuke Honda, Ryusuke Sakamoto, Kazutaka Narita, Tomomitsu Sasaki, Daisuke Okui, Kenjiro Kimura
2018 Clinical and Experimental Nephrology  
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
more » ... croalbuminuria 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-tocreatinine 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 m 2 , 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.
doi:10.1007/s10157-018-1530-1 pmid:29372470 fatcat:2miew3orv5bena46egllwjavya