Effects of Citrate Mixture on Gout Flares During Urate-Lowering Therapy Initiation Among Chinese Male Underexcretion-Type Gout Patients: A Prospective Cohort Study

Purpose: To evaluate the effect of urine alkalization with citrate mixture on reducing flare incidence during initial urate-lowering therapy period in male gout patients with renal underexcretion-type. Patients and Methods: In this prospective cohort study, patients with renal underexcretion and urinary pH < 6.2 were enrolled. All participants received febuxostat 20 mg/day during weeks 0– 4, later increased to 40 mg/day if serum urate (SU) levels > 360 μmol/L. According to group assignment, patients received either alkalization therapy (Alk group; citrate mixture, 3.5 g twice/day) or no alkalization (Control group). The primary outcome measure was gout flare incidence. Results: In total, 240 patients (Alk 114, Control 126) completed the 12-week follow-up. The Alk group had a significantly lower flare incidence (35.1%) than the Control group (59.5%, P < 0.001) and a lower recurrence of flares (14.0% vs. 31.0%, P = 0.002). At week 4, the proportion of participants with SU < 360 μmol/L was significantly higher in the Alk than in the Control group ( P = 0.039). The Alk group had lower triglycerides and higher high-density lipoprotein cholesterol levels than the Control group at weeks 4, 8, and 12 ( P < 0.05). The urinary albumin-to-creatinine ratio (UACR) decreased from 1.65 (0.36– 7.01) to 1.08 (0.62– 2.99) at week 12 in the Alk group, significantly lower than that in the Control group ( P = 0.001). No significant difference was noted in the incidence of adverse events between groups. Conclusion: In patients with renal underexcretion gout, urine alkalization with febuxostat therapy prevented gout flares, improved lipid metabolism, and lowered UACR. Study Registration: ChiCTR, https://www.chictr.org.cn , ChiCTR2100043573.