Changes in uric acid levels and estimated glomerular filtration rate slope after treatment with dotinurad in patients with hyperuricemia

Hyperuricemia is a recognized risk factor for chronic kidney disease (CKD). Dotinurad, a novel selective urate reabsorption inhibitor, effectively lowers uric acid (UA) levels. However, longitudinal patterns of UA after treatment initiation and changes in estimated glomerular filtration rate (eGFR) slope across the pre-initiation and post-initiation periods remain insufficiently characterized. We retrospectively identified patients with hyperuricemia who initiated dotinurad therapy. Eligible patients required a baseline eGFR and at least two eGFR measurements during both the pre-initiation period (3, 6, or 12 months before initiation) and the post-initiation period (3, 6, or 12 months after initiation). UA levels were assessed at baseline and at 3, 6, and 12 months. Longitudinal changes in UA and eGFR slopes were evaluated using linear mixed-effects models. Among 135 screened patients, 68 met the inclusion criteria. The mean age was 59 years, and 73.5% were male. The median baseline eGFR was 50.4 mL/min/1.73 m². UA levels were lower at 3, 6, and 12 months compared with baseline (all P < 0.001). The annual eGFR slope was − 5.7 mL/min/1.73 m²/year (95% confidence interval [CI] − 8.3 to − 3.2) before initiation and 0.6 mL/min/1.73 m²/year (95% CI − 0.6 to 1.8) after initiation. The difference in slopes was statistically significant (P for interaction = 0.003). Similar patterns were observed in multivariable models adjusted for baseline eGFR, age, sex, and sodium–glucose cotransporter 2 inhibitor use. In this retrospective cohort, dotinurad use was associated with lower UA levels and a less negative eGFR slope over time. These findings describe real-world patterns of UA levels after treatment initiation and changes in eGFR slope before and after treatment initiation, and they support the need for prospective studies evaluating kidney outcomes.