In patients with gout, the use of citrate mixture is superior to that of sodium bicarbonate in lowering the incidence of urine occult blood and the frequency of gout attacks, according to study results published in Rheumatology (Oxford). However, the efficacy of citrate mixture and sodium bicarbonate is comparable, without any significant adverse events.

Researchers sought to compare the safety and efficacy of citrate mixture and sodium bicarbonate on urine alkalization in patients with gout receiving treatment with benzbromarone.

A prospective, randomized, parallel-controlled study (China Clinical Trial Registration Number: ChiCTR1800018518) was conducted in the gout clinic of the Affiliated Hospital of Qingdao University in Qingdao, China. Study inclusion criteria were patients aged between 18 and 70 years and fulfilment of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) clinical diagnostic criteria for gout. Participants enrolled in the study underwent a 14-day washout period with a low-purine diet and drug washout.

Continue Reading

Patients were randomly assigned in a 1:1 ratio to receive either sodium bicarbonate or citrate mixture. They received urate-lowering treatment and urine alkalization therapy (sodium bicarbonate 1 g thrice daily; citrate mixture 3.5 g twice daily) for 12 weeks. In addition, benzbromarone was administered initially at a 25-mg/day dose, then maintained at a dose of 50 mg/day, along with 2000 to 2500 mL of water daily.

Overall, 182 patients completed the 12-week urine alkalization study. In both groups, the urine pH value increased significantly from baseline to follow-up (P <.05). Median urine pH was elevated by 9.1% in the sodium bicarbonate group (from 5.50 [95% CI, 5.43-5.57] to 6.00 [95% CI, 5.81-6.05]) and by 7.2% in the citrate mixture group (from 5.53 [95% CI, 5.48-5.63] to 5.93 [95% CI, 5.80-6.01]).

Further, the estimated glomerular filtration rate decreased significantly after 12 weeks of treatment in the sodium bicarbonate group (P <.01), whereas it remained comparable between baseline and the last follow-up in the citrate mixture group (P >.05). Urine analysis results showed that the incidence rate of occult blood in the sodium bicarbonate group was higher than that in the citrate mixture group (38% vs 24%, respectively; P <.05), with a similar occurrence of kidney stones in both groups.

At the 12-week follow-up, the frequency of twice gout flare was statistically significantly lower in the citrate mixture group than in the sodium bicarbonate group (4% vs 12%, respectively; P =.037). There were no treatment-emergent adverse events reported in either group.

Study limitations included the lack of generalizability of the population and the lack of detailed research on urine components, particularly citrate ions.

Researchers concluded that a standardized method of urine pH determination should be incorporated during monitoring procedures, with the current trial highlighting the importance of urine alkalization in patients with gout.


Xue X, Liu Z, Li X, et al. The efficacy and safety of citrate mixture vs sodium bicarbonate on urine alkalization in Chinese primary gout patients with benzbromarone: a prospective, randomized controlled study. Rheumatology (Oxford). Published online November 19, 2020. doi:10.1093/rheumatology/keaa668

This article originally appeared on Rheumatology Advisor