Effects of topiroxostat on the serum urate levels and urinary albumin excretion in hyperuricemic stage 3 chronic kidney disease patients with or without gout

Abstract

Background: Topiroxostat, a selective xanthine oxidase inhibitor, shows effective reduction in the serum urate level in hyperuricemic patients with or without gout. The objective of this study was to evaluate the efficacy and safety of topiroxostat in hyperuricemic stage 3 chronic kidney disease patients with or without gout.

Methods: The study design was a 22-week, randomized, multicenter, double-blind study. The enrolled patients were randomly assigned to treatment with topiroxostat 160 mg/day (n = 62) or to the placebo (n = 61). The endpoints were the percent change in the serum urate level, change in the estimated glomerular filtration rate, the urinary albumin-to-creatinine ratio, the proportion of patients with serum urate levels of 356.88 μmol/L or less, blood pressure, and serum adiponectin.

Results: After 22 weeks, although the changes in the estimated glomerular filtration rate and blood pressure were not significant, the percent change in the serum urate level (-45.38 vs. -0.08 %, P < 0.0001) and the percent change in urinary albumin-to-creatinine ratio (-33.0 vs. -6.0 %, P = 0.0092) were found to have decreased in the topiroxostat as compared with the placebo. Although the incidence of 'alanine aminotransferase increased' was higher in the topiroxostat, serious adverse event rates were similar in the two groups.

Conclusion: Topiroxostat 160 mg effectively reduced the serum urate level in the hyperuricemic stage 3 chronic kidney disease patients with or without gout.

Fig. 1

Patient distribution. Asterisk discontinuance criteria (serum urate <118.96 μmol/L)

Fig. 2

Percent change of the serum urate levels and proportion of patients with serum urate levels ≤356.88 μmol/L at the final visit (intent-to-treat population). a Percent change of the serum urate level from the baseline to the final visit. Results are expressed as mean ± SD. b Proportion of patients with serum urate levels ≤356.88 μmol/L at the final visit. Results are expressed as percentages and its 95 % CIs. Two patients of the topiroxostat group were withdrawn without measurement of the serum urate levels during the study. Therefore, these patients were excluded from this analysis. SD standard deviation, CI confidential interval

Fig. 3

Change of the eGFR and ACR from the baseline to the final visit (intent-to-treat population). a Changes of the eGFR from the baseline to the final visit. Results are expressed as point estimates and its 95 % CIs by ANCOVA. Covariates: baseline eGFR, baseline ACR, baseline HbA1c. b Percentage of the ACR from the baseline to the final visit. Results are expressed as point estimates and its 95 % CIs as calculated by ANCOVA. Covariate: baseline ACR. eGFR estimated glomerular filtration rate, ACR urinary albumin-to-creatinine ratio, SD standard deviation, CI confidential interval, ANCOVA analysis of covariance

Fig. 4

Changes of the eGFR and ACR from the baseline to each visit (intent-to-treat population). a Changes of the eGFR from the baseline to each visit. Results are expressed as mean ± SD. b Percent changes of the ACR from the baseline to each visit. Results are expressed as means and its 95 % CIs. eGFR estimated glomerular filtration rate, ACR urinary albumin-to-creatinine ratio, SD standard deviation, CI confidential interval

Fig. 5

Correlation between the baseline ACR and the change in the ACR from the baseline to the final visit in each group. a Topiroxostat group (n = 62). b Placebo (n = 60). ACR Urinary albumin-to-creatinine ratio, r _P Pearson’s correlation coefficient