To compare the efficacy and safety of Firsekibart versus compound betamethasone in gout patients with different estimated glomerular filtration rate (eGFR) levels. Methods: Patients were randomized, double blinded and separated into two equal groups to receive a single dose of Firsekibart (200 mg) or compound betamethasone (7 mg). Patients were divided into three subgroups according to baseline eGFR: ≥ 90, 60–89, and 30–59 mL/min/1.73 m² to evaluate 72-hour pain relief, 12/24-week recurrence rate, renal function changes, and safety events. Results: Of 311 patients in full analysis set (FAS), 113 (36.3%) had baseline eGFR 60–89 mL/min/1.73 m², and 42 (13.5%) had baseline eGFR 30–59 mL/min/1.73 m². Similar reduction in visual analogue scale (VAS) scores at 72-hour was observed in each eGFR subgroup between Firsekibart and compound betamethasone group (p > 0.05). Compared with compound betamethasone, Firsekibart reduced the risk of recurrence at 12/24 weeks in patients with different eGFR subgroups (all p < 0.0001). In safety evaluation, no obvious changes of creatinine and eGFR were observed in each subgroup during 24-week follow up. Treatment emergent adverse events (TEAEs) incidence was comparable in each eGFR subgroup analysis. In total, 1 (0.6%) patient experienced emergent serious adverse events (TESAE) and 0 treatment-related adverse events (TRSAE) was reported in the Firsekibart group compared to 6 (3.8%) and 3 (1.9%) in the compound betamethasone group, respectively. Conclusion: Overall, Firsekibart demonstrated non-inferior short-term pain relief while offering better prevention of new flares, with a lower incidence of serious adverse events compared to compound betamethasone, and results were consistent across eGFR subgroups. Both Firsekibart and compound betamethasone showed little effect on renal function.