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Kidney Week

Abstract: FR-PO251

The Mechanism of Anti-Albuminuric Effect by Topiroxostat

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Kato, Sawako, Nagoya University Graduate School of Medicine, Aichi, NAGOYA, Japan
  • Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Aichi, NAGOYA, Japan
  • Kobori, Hiroyuki, Tulane University Hypertension and Renal COE, New Orleans, Louisiana, United States
Background

In 2018, we demonstrated the anti-albuminuric effect of topiroxostat, a selective xanthine oxidoreductase inhibitor (XORi), in the ETUDE trial (24-week, multicenter, open-label, randomized trial; 1:1, high dose vs low dose) for hyperuricemic patients with diabetic nephropathy. XORis have been reported to have renoprotective power via reduction of oxidative stress, inflammation, and renin angiotensin system (RAS) activation. Therefore, we investigated reduction in oxidative stress (8OH-dG), inflammation (MCP-1) and RAS activation (angiotensinogen) in urine samples of patients actually administered topiroxostat.

Methods

Urinary levels of 8OH-dG, MCP-1 and angiotensinogen in the samples collected in the ETUDE study were measured. We compared these parameters between high dose and low dose of topiroxostat by analysis of variance (ANOVA) using the treatment group, eGFR, age and gender and the baseline levels as fixed effects. In addition, in each group of high dose and low dose of topiroxostat, the intra-group comparison was performed by t-test with the changes in these parameters after intervention relative to the baseline values.

Results

There was no significant differences in changes in 8OH-dG, MCP-1 and angiotensinogen between the two treatment groups by ANOVA (P = 0.69, 0.59 and 0.50, respectively). In comparison with the baseline values at the end of intervention, 8OH-dG (P = 0.08 high dose, 0.24 low dose) and MCP-1 increased in high dose group (P = 0.02 high dose, 0.51 low dose). The levels of angiotensinogen showed no statistically significant increase as well as decrease (P = 0.48 high dose, 0.72 low dose).

Conclusion

Our additional analysis failed to detect any suppressive effect of inflammation, oxidative stress and RAS activation with topiroxostat and could not reach an evidence that led to the mechanism of albuminuria lowering action.

Funding

  • Commercial Support