Effects of Adding Urinary Alkalizer Citrate Mixture to Febuxostat in Gout Patients with Combined-type Hyperuricemia and Acidic Urine: A Prospective Cohort Study

Background People with gout and combined-type hyperuricemia, defined as renal urate overload and renal urate under-excretion, have diminished responsiveness to urate-lowering therapy. Emerging observational data suggest that urine alkalization might improve responsiveness to febuxostat. Hence, this prospective study evaluated the urate-lowering efficacy of citrate mixture added to febuxostat in people with gout and combined-type hyperuricemia. Methods Patients with combined-type hyperuricemia and low urine pH (< 6.2) were prospectively enrolled from a gout clinic. All were treated with febuxostat (initially 20 mg daily, escalated to 40 mg daily if serum urate (SU) ≥ 360µmol/L). Citrate mixture (3.5g twice daily, open label) was added according to shared decision of both physician and patient (alkalization vs. non-alkalization). Participants were followed for 12 weeks, with primary endpoint being achievement of SU < 360 µmol/L at final assessment. Results We enrolled 234 eligible patients, with 194 completing 12 weeks follow-up (98 non-alkalization and 96 with alkalization). At week 12, more patients in the alkalization group achieved SU < 360µmol/L (57% vs. 40%, P  < 0.05), with significantly increased renal urate excretion, and lower febuxostat doses (mean ± S.D, 31.88 ± 9.88 vs. 34.69 ± 8.88 mg, P  < 0.05). Additionally, metabolic measures including the triglyceride concentration and triglyceride-glucose index were lower, and high-density lipoprotein cholesterol concentration as well as insulin sensitivity were higher in the alkalization group. The incidence of adverse events was similar between groups. Conclusions In people with gout and combined-type hyperuricemia, adjunctive urine alkalization with febuxostat demonstrated superior urate-lowering response, along with improvement in metabolic abnormalities. Trial registration ChiCTR, http://www.chictr.org.cn, ChiCTR2100043573.