--- title: Two gout drugs, one uric acid target, different stone risks. Korean data separate them publication: Medical Insights Korea section: news category: Kidney Stones canonical_url: https://medicalinsightskorea.com/news/gout-drug-choice-urolithiasis-risk-korea author: Andrew Cho published: 2026-09-15T09:00:00+09:00 modified: 2026-09-15T09:00:00+09:00 content_type: reporting license: Quotation permitted with attribution to Medical Insights Korea and a link to the canonical URL. --- # Two gout drugs, one uric acid target, different stone risks. Korean data separate them Allopurinol lowers urate by making less of it; benzbromarone lowers it by pushing more into the urine. In 61,300 matched Korean patients, the second route carried a 56 percent higher rate of urinary stones. ## Answer In a cohort study using the Korea National Health Insurance Service database from 2011 to 2020, gout patients starting allopurinol as first-line urate-lowering treatment had a lower rate of new urinary stones than propensity-score matched patients starting benzbromarone — 0.87 versus 1.39 cases per 100 person-years over a mean follow-up of 322 days, a hazard ratio of 0.64 (95% CI 0.51 to 0.80) — and the difference held for stones requiring intervention, with a hazard ratio of 0.61 (95% CI 0.43 to 0.88). ## Key takeaways - A Korea National Health Insurance Service cohort study matched 61,300 patients starting allopurinol for gout against 12,260 starting benzbromarone, five to one, on more than 80 variables. - Over a mean follow-up of 322 days, 619 cases of urolithiasis occurred: 0.87 per 100 person-years on allopurinol against 1.39 on benzbromarone, a hazard ratio of 0.64 (95% CI 0.51 to 0.80). - About 44 percent of the urinary stones required intervention, and the difference persisted for that outcome with a hazard ratio of 0.61 (95% CI 0.43 to 0.88). - The lower risk on allopurinol held across subgroups by age, sex, thiazide use and cardiovascular risk, and was larger in the high cardiovascular risk subgroup, with a P value for interaction of 0.02. - The two drugs lower urate by opposite routes: allopurinol inhibits xanthine oxidase and reduces urate production, while benzbromarone is a uricosuric that increases urate excretion into the urine. - Uric acid accounted for 19.61 percent of 33,078 Korean urinary stone analyses between 2014 and 2019, rising with age and more common in men than women at 24.5 percent against 11.0 percent. - The 2024 European Association of Urology guideline classes uric acid stone formers as at high risk of relapse. ## Full article Gout and urinary stones share a chemical. Roughly a fifth of stones analysed in Korea are uric acid, and the men in whom gout concentrates are the men in whom uric acid stones concentrate. What has been less obvious is that the two commonest ways of lowering urate do not carry the same stone risk, and that Korea is one of the few countries with the data to show it. ### Two drugs, two mechanisms, one target Allopurinol is a xanthine oxidase inhibitor: it lowers serum urate by reducing how much the body makes. Benzbromarone is a uricosuric: it lowers serum urate by increasing how much the kidney excretes. Both bring the blood number down. Only one of them does it by sending more urate through the urinary tract, which is where stones form. The mechanistic worry is therefore old. What was missing was a comparison at scale in ordinary practice, and it was missing partly for a reason of geography: benzbromarone is not marketed in the United States, so the largest pharmacoepidemiology databases in the world cannot answer the question. Korea prescribes both. ### What the national comparison found A study published in Rheumatology used the Korea National Health Insurance Service database covering 2011 to 2020, identifying gout patients starting either drug as their first urate-lowering treatment. Propensity-score matching on more than 80 variables produced 61,300 allopurinol initiators matched five to one against 12,260 benzbromarone initiators, with a mean age of 59 and 79 percent men. **New urinary stones by first-line urate-lowering drug, Korea 2011–2020** | | Allopurinol | Benzbromarone | Hazard ratio (95% CI) | | --- | --- | --- | --- | | Urolithiasis, per 100 person-years | 0.87 | 1.39 | 0.64 (0.51–0.80) | | Stone requiring intervention | — | — | 0.61 (0.43–0.88) | Six hundred and nineteen cases of urolithiasis occurred over a mean follow-up of 322 days. Around 44 percent of those stones required an intervention, and the advantage for allopurinol was, if anything, slightly larger for that harder outcome than for stones overall — which is the direction that matters, because a difference visible only in diagnostic codes and not in procedures would be easy to dismiss as differential scanning. **0.87 vs 1.39** — new urinary stones per 100 person-years on allopurinol versus benzbromarone among matched Korean gout patients _Source: Kang EH et al., Rheumatology, 2024_ The lower risk on allopurinol persisted across subgroups defined by age, sex, thiazide use and cardiovascular risk. It was larger in patients at high cardiovascular risk than in those who were not, with a P value for interaction of 0.02 — a signal the authors report and do not over-explain, and neither will we. ### Why this lands harder in Korea The Korean Society of Endourology and Robotics research series analysed 33,078 urinary stone compositions collected between January 2014 and June 2019. Uric acid was 19.61 percent of the total, third behind calcium oxalate at 46.41 percent and struvite at 29.66 percent. - Uric acid stones were more common in men than women: 24.5 percent against 11.0 percent. - The proportion of uric acid stones rose with age, while calcium oxalate fell. - Uric acid stones were least common in the capital region. Set that against the gout cohort — mean age 59, 79 percent men — and the overlap is close to exact. The patients being started on urate-lowering therapy in Korea are demographically the same patients whose stones, when they form, are most likely to be uric acid. > **The relapse risk that sits behind this** > The 2024 European Association of Urology guideline update places uric acid stone formers, together with infection and cystine stone formers, in the group at high risk of relapse outright — not conditionally, and not only after a second stone. For a Korean man in his late fifties starting urate-lowering therapy, that is the context in which a choice between two drugs of comparable urate-lowering efficacy stops being a matter of indifference. ### What the study leaves open This is not a randomised trial. Propensity-score matching on more than 80 variables is a serious attempt to make the two groups comparable, and it still cannot balance what the claims never recorded: serum urate levels achieved, urine pH, fluid intake, or whether a patient was already alkalinising their urine. Urine pH in particular is the variable that governs uric acid crystallisation, and it is absent from every claim in the database. The follow-up is short — a mean of 322 days, under a year, in a disease that recurs over decades. And the finding does not say benzbromarone should not be used. It says that when two drugs reach the same urate target by opposite routes, the route that runs through the urine carries a measurable stone cost, and that the cost is largest in exactly the population most likely to be prescribed it. The practical reading is a question to raise rather than a rule to follow: a gout patient with a history of urinary stones, or with the age and sex profile in which uric acid stones cluster, has a reason to ask which mechanism their urate-lowering drug uses. Most patients have never been told there is more than one. ## Sources - Kang EH, Shin A, Park CS, Lee EB, Lee YJ, Curhan G, Choi HK. Risk of urolithiasis associated with allopurinol versus benzbromarone among patients with gout: a population-based cohort study. Rheumatology 2024;63(9):2433-2441. doi:10.1093/rheumatology/keae262. PMID:38733596. https://doi.org/10.1093/rheumatology/keae262 - Jung HD, Seo IY, Lee JY. Large database study of urinary stone composition in South Korea: Korean Society of Endourology and Robotics (KSER) research series. Investigative and Clinical Urology 2021;62(4):462-469. doi:10.4111/icu.20210039. PMID:34190438. https://doi.org/10.4111/icu.20210039 - Skolarikos A, Somani B, Neisius A, Jung H, Petřík A, Tailly T, Davis N, Tzelves L, et al. Metabolic evaluation and recurrence prevention for urinary stone patients: an EAU guidelines update. European Urology 2024;86(4):343-363. doi:10.1016/j.eururo.2024.05.029. PMID:39069389. https://doi.org/10.1016/j.eururo.2024.05.029 ## Citation Andrew Cho (2026). "Two gout drugs, one uric acid target, different stone risks. Korean data separate them". Medical Insights Korea. https://medicalinsightskorea.com/news/gout-drug-choice-urolithiasis-risk-korea Retrieved from https://medicalinsightskorea.com/news/gout-drug-choice-urolithiasis-risk-korea