Journal Article

Effects of adding urinary alkalizer citrate mixture to febuxostat in gout patients with combined-type hyperuricemia and low urine pH: a prospective cohort study

Ji, Xiaopeng, Zhang, Hui, Li, Changgui, Dalbeth, Nicola, Wang, Can, Chen, Ying, Cui, Lingling, Han, Lin, Liu, Zhen, Sun, Mingshu, Guo, Kai, Li, Xinde, He, Yuwei, Terkeltaub, Robert, Wang, Xuefeng, Ji, Aichang, Sun, Wenyan, Lu, Jie

2026

Overview

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 (3.5 g 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 (57.3% vs. 39.8%, P  < 0.05), with significantly increased renal urate excretion, and lower febuxostat doses (mean ± S.D, 31.9 ± 9.9 vs. 34.7 ± 8.9 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 Adjunctive urine alkalization with febuxostat demonstrated a superior urate-lowering response and improved metabolic abnormalities in male with gout and combined-type hyperuricemia. Trial registration ChiCTR, http://www.chictr.org.cn , ChiCTR2100043573.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Aged / Blood pressure / Body mass index / Care and treatment / Cholesterol / Chronic illnesses / Citric Acid - administration & dosage / Citric Acid - therapeutic use / Clinical outcomes / Clinical trials / Cohort analysis / Cohort Studies / Combined-type hyperuricemia / Complications and side effects / Diagnosis / Drug dosages / Drug therapy / Drug Therapy, Combination / Febuxostat - administration & dosage / Febuxostat - therapeutic use / Female / Gout / Gout - complications / Gout - drug therapy / Gout - urine / Gout flare / Gout Suppressants - administration & dosage / Gout Suppressants - therapeutic use / Health aspects / Humans / Hydrogen-Ion Concentration / Hyperuricemia / Hyperuricemia - complications / Hyperuricemia - drug therapy / Hyperuricemia - urine / Insulin resistance / Kidney diseases / Kidney stones / Male / Measurement / Medicine / Medicine & Public Health / Metabolic syndrome / Middle Aged / Orthopedics / Patients / Potassium / Prospective Studies / Rheumatism / Rheumatology / Risk factors / Serum urate / Treatment Outcome / Type 2 diabetes / Uric acid / Uric Acid - blood / Uric Acid - urine / Urinary tract diseases / Urine / Urine alkalization