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


CONCLUSIONS
Topiroxostat 160 mg effectively reduced the serum urate level in the hyperuricemic stage 3 chronic kidney disease patients with or without gout.
Department of Pathophysiology and Therapy in Chronic Kidney Disease, Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan, t-hosoya@jikei.ac.jp.
Tatsuo
T
Hosoya
Iwao
I
Ohno
Shinsuke
S
Nomura
Ichiro
I
Hisatome
Shunya
S
Uchida
Shin
S
Fujimori
Tetsuya
T
Yamamoto
Shigeko
S
Hara
D052242:Adiponectin / Q000097:blood; D000368:Aged; D000419:Albuminuria / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D015897:Comorbidity; D003404:Creatinine / Q000652:urine; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006073:Gout / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use; D015995:Prevalence; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D052242:Adiponectin; D004791:Enzyme Inhibitors; D009570:Nitriles; D011725:Pyridines; C504882:FYX-051; D014527:Uric Acid; D003404:Creatinine; D014969:Xanthine Oxidase