Impact of adding urine alkalization therapy to xanthine oxidase inhibitor in gout management: a prospective cohort study

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 TG 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. Clinical Trial Registration This project was registered in ChiCTR (www.chictr.org.cn), with registration number: ChiCTR2100043573.