Dotinurad Treatment for Patients With Hyperuricemia Complicating CKD

Area of Science:

• Nephrology
• Pharmacology

Background:

• Hyperuricemia management is crucial for reducing cardiovascular risk and slowing renal injury progression in chronic kidney disease (CKD).
• Novel therapeutic agents are needed to effectively manage hyperuricemia in CKD patients.

Purpose of the Study:

• To assess the efficacy and safety of dotinurad, a urate transporter-1 inhibitor, in patients with hyperuricemia and CKD.
• To compare the effectiveness of dotinurad in different stages of chronic kidney disease.

Main Methods:

• A nonrandomized, parallel interventional study involving patients with hyperuricemia and CKD, grouped by estimated glomerular filtration rate (eGFR).
• Dotinurad dosage was titrated from 0.5 mg/d to 2-4 mg/d, with primary endpoint being noninferiority of serum uric acid (UA) reduction at 24 weeks.
• Secondary endpoints included changes in eGFR and UA clearance-to-creatinine clearance ratio (C_UA/C_Cr), along with safety assessments.

Main Results:

• Dotinurad achieved significant mean serum UA reductions of 47.2% (G1/G2) and 42.8% (G3/G4) at 24 weeks, demonstrating noninferiority in CKD stages G3/G4.
• A slight increase in eGFR was observed, suggesting counteraction of spontaneous decline, and C_UA/C_Cr generally increased over the study period.
• No new safety concerns were identified, and urinary pH remained stable.

Conclusions:

• Dotinurad therapy appears well-tolerated and effective for hyperuricemia in CKD patients.
• The drug shows comparable efficacy to standard treatments in CKD stages G3/G4.
• Further randomized controlled trials in larger patient cohorts are warranted to confirm these findings.