Abstract
OBJECTIVES: Gout patients frequently have decreased urine pH, related to metabolic syndrome (MetS) and chronic kidney disease. Here, we aimed to investigate whether the addition of urine alkalization to urate-lowering therapy (ULT) is associated with improvements in albuminuria, gout flares or MetS outcomes in men with gout and low urinary pH (pH < 6.2). METHODS: A prospective cohort study enrolled 385 participants starting ULT with febuxostat (initially 20 mg daily, escalated to 40 mg daily if serum urate ≥360 µmol/l), with or without alkalization based on patient preference using a 3.5 g bid citrate mixture. Participants were followed every 4 weeks to week 12. The primary outcome was urine albumin-to-creatinine ratio (UACR) at week 12. RESULTS: In total, 343 participants completed the week 12 visit (137 alkalization, 206 controls). At week 12, compared with controls, participants receiving alkalization required a significantly lower febuxostat dose (by ∼20%) but had no significant difference in serum urate at target <360 µmol/l. Urine pH increased significantly in the alkalization group from week 4 (P < 0.001). At week 12, the alkalization group had a significantly lower UACR compared with control (P < 0.001), without significantly different eGFR. Participants in the alkalization group experienced fewer gout flares and had lower pain visual analogue scale scores (P < 0.001). There were lower serum triglyceride levels (P < 0.01) and higher HDL-C levels (P < 0.001) in the alkalization group. No other differences in metabolic outcomes were observed. CONCLUSION: Urine alkalization was associated with lower UACR, fewer gout flares, and improved serum lipid profile in febuxostat-treated men with gout and low urine pH. TRIAL REGISTRATION: ChiCTR, http://www.chictr.org.cn, ChiCTR2100043573.