Comparative study of a novel selective urate reabsorption inhibitor "dotinurad" among patient groups with different stages of renal dysfunction

Clin Exp Nephrol. 2021 Dec;25(12):1336-1345. doi: 10.1007/s10157-021-02115-7. Epub 2021 Jul 30.

Abstract

Background: Dotinurad is a selective urate reabsorption inhibitor (SURI), which selectively inhibits URAT1 to lower serum uric acid levels in patients with hyperuricemia. Herein, the effects of dotinurad were compared among patient groups with different stages of renal dysfunction.

Methods: Patient data from four clinical trials were pooled and divided into four groups according to the stage of renal dysfunction to compare the effects of dotinurad at different stages. The grouping (stages G1-G3b) was based on the estimated glomerular filtration rate (eGFR) of the patients. In addition, patient data from a long-term study (34 or 58 weeks) were evaluated in the same manner.

Results: In the pooled analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 64.7-100.0% at a dose of 2 or 4 mg. In the long-term analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 60.0-100.0% at a dose of 2 or 4 mg. Although the outcomes in stage G3b were worse due to higher baseline serum uric acid levels, satisfactory outcomes were observed in all stages. Even in stages G3a and G3b, when renal function declined, the eGFR remained constant throughout the dose period.

Conclusion: The efficacy of dotinurad was confirmed in hyperuricemic patients with normal renal function (stage G1) and mild to moderate renal dysfunction (stage G2-G3b). Dotinurad was found to be effective in the treatment of hyperuricemia in patients with mild to moderate renal dysfunction.

Keywords: Chronic kidney disease; Dotinurad; Hyperuricemia; Selective urate reabsorption inhibitor; URAT1 inhibitor.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Benzothiazoles / adverse effects
  • Benzothiazoles / therapeutic use*
  • Biomarkers / blood
  • Clinical Trials as Topic
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Hyperuricemia / blood
  • Hyperuricemia / diagnosis
  • Hyperuricemia / drug therapy*
  • Hyperuricemia / physiopathology
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / physiopathology
  • Kidney Diseases / diagnosis
  • Kidney Diseases / physiopathology*
  • Male
  • Middle Aged
  • Renal Reabsorption / drug effects*
  • Treatment Outcome
  • Uric Acid / blood*
  • Uricosuric Agents / adverse effects
  • Uricosuric Agents / therapeutic use*

Substances

  • Benzothiazoles
  • Biomarkers
  • Uricosuric Agents
  • Uric Acid
  • dotinurad