Abstract Introduction Hyperuricemia (HUA) is a residual risk factor of cardiovascular disease (CVD). Patients with HUA frequently experience hypertension, which is the main risk factor for CVD. In terms of cardiorenal syndrome, it is crucial to prevent the progression of chronic kidney disease (CKD) to prevent CVD. Although HUA is associated with the progression of CKD, there is no consensus about the prevention of CKD progression by uric acid (UA) lowering therapy. Dotinurad is a new UA-lowering drug that selectively inhibits urate transporter 1 in the renal proximal tubule. However, its efficacy in lowering serum UA levels and renal function in patients with HUA and hypertension remains unclear. Purpose Therefore, this study aimed to assess the effects of dotinurad on UA and renal function in patients with HUA and hypertension. Methods We analyzed outpatients with HUA and hypertension who newly received dotinurad between May 2021 and December 2023. Their eGFR slope before and after the administration was determined by the linear mixed model using eGFR of pre-twelve months, six months, pre-three months, baseline, post-three months, post-six months, and post-twelve months. The change of eGFR slope before and after the administration was assessed. The relationship between the change of UA(ΔUA) and eGFR (ΔeGFR) baseline and post-six months was also analyzed. Results Sixty-eight patients (mean age 59.5±16.5 years, with 73.5% men) were included in the analysis. Serum UA significantly decreased (baseline:9.0±1.6 mg/dL vs. post-six months:6.6±1.6 mg/dL, P0.001). Although eGFR was not improved (baseline: 50.4 (32.9-63.3) mL/min/1.73m2 vs. post-six months: 54.0 (34.2-69.5) mL/min/1.73m2, P = 0.086), eGFR slope was significantly improved (before administration: -5.73 mL/min/1.73m2/year vs. after administration:0.64 mL/min/1.73m2/year; P for interaction = 0.003) (Figure1). There is a significant relationship between ΔUA and ΔeGFR (r = -0.374, P = 0.005). Multiple regression analysis revealed that ΔUA was negatively associated with ΔeGFR after adjustment for age, sex, and BMI (95% confidence interval; -2.5 to -0.4, P = 0.008). ). There is a significant relationship between ΔUA and ΔeGFR (r = -0.374, P = 0.005). Multiple regression analysis revealed that ΔUA was negatively associated with ΔeGFR after adjustment for age, sex, and BMI (95% confidence interval; -2.5 to -0.4, P = 0.008). Conclusions Dotinurad may prevent renal function from worsening in patients with HUA and hypertension. This effect may depend on the amount of UA reduction.
Mizoguchi et al. (Sat,) studied this question.
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