Changes in kidney function during dotinurad treatment for hyperuricemia: a systematic review

Hyperuricemia and chronic kidney disease (CKD) are bidirectionally linked; however, studies have shown that urate-lowering therapy with xanthine oxidoreductase inhibitors is largely neutral in regards to renal outcomes. Dotinurad, a selective urate reabsorption inhibitor (SURI) that inhibits URAT1 without impacting ABCG2, OAT1, and OAT3, may exert distinct renal effects; however, clinical evidence regarding its renal impact is dispersed across small studies. In this systematic review, we described changes in estimated glomerular filtration rate (eGFR) during dotinurad treatment given for hyperuricemia.

We systematically searched the PubMed, Embase, CENTRAL, Ichushi-Web, and J-STAGE databases from inception to May 2026 for studies evaluating dotinurad and eGFR. Eligible studies were synthesized descriptively owing to substantial clinical and methodological heterogeneity.

Sixteen studies encompassing 1323 dotinurad-treated patients (1 randomized trial, 4 nonrandomized comparative studies, and 11 single-arm before-after studies) presented 24 study-level eGFR estimates (baseline mean eGFR approximately 20-100 mL/min/1.73 m²; follow-up 12-52 weeks). Across these studies, eGFR showed no significant decline, remaining generally stable or slightly increasing. In the five comparative studies, between-group differences (dotinurad minus comparator) ranged from +0.5 to +3.5 mL/min/1.73 m² (or per year for slopes), with 95% confidence intervals including zero in four.

In the available short-term studies, eGFR generally remained stable during dotinurad treatment in patients with hyperuricemia, including those with CKD. Between-group estimates from five comparative studies were generally imprecise and did not provide consistent evidence of a treatment-related improvement in kidney function. Further randomized trials with prespecified renal end points are warranted.