Expert consensus on urate‑lowering therapy for high‑risk hyperuricemia (2026 edition)

Hyperuricemia (HUA) is a common chronic condition diagnosed when serum uric acid (SUA) exceeds 420 μmol/L (7.0 mg/dL) on two separate occasions. The prevalence of HUA in China has shown a marked upward trend, increasing from 11.1% in 2015–2016 to 14.0% in 2018–2019.[1,2] Although established recommendations are available for urate-lowering therapy (ULT) in gout, substantial controversy remains regarding ULT strategies for high-risk hyperuricemia (HrHUA), especially HrHUA with nephrolithiasis, chronic kidney disease, cardiovascular disorders, and metabolic comorbidities.[3–5] To address these challenges, the Chinese Rheumatology Association and the Committee for Rheumatologists and Immunologists of Chinese Primary Health Care Foundation convened national experts to develop this consensus. The consensus aimed to define HrHUA, optimize ULT strategies for this population, and provide evidence-based guidance for comorbidity-specific management. This consensus was registered in the International Practice Guideline Registry Platform in English and Chinese (PREPARE‑2024CN998). For each clinical question, explicit inclusion and exclusion criteria were defined, and relevant evidence was systematically collected. Evidence was graded according to the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence. For important clinical questions that were not amenable to conventional evidence quality rating methods, the consensus panel issued expert consensus-based recommendations in the form of Good Practice Statements (GPS). A systematic search was conducted in PubMed, Embase, Web of Science, and Cochrane Library through 1 March 2024. Randomized controlled trials (RCTs), cohort studies, meta-analyses, and consensus statements on ULT in HrHUA were included. Non-English studies were screened for eligibility; preprints and abstracts-only were excluded. Overlapping cohorts were de-duplicated by retaining the study with the most complete data. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow and full search strategies are detailed in Supplementary Material, https://links.lww.com/CM9/C928. Final recommendations were formulated through structured expert voting and categorized as strong or weak according to predefined thresholds. This consensus summarizes the available evidence and provides practical guidance for the definition, evaluation, and management of HrHUA in China. Detailed additional supporting information is provided in the Supplementary Material, https://links.lww.com/CM9/C928. Clinical question 1: Which patients with HUA are defined as HrHUA? Consensus 1: HrHUA denotes a clinical state in which HUA coexists with comorbid conditions known to predispose patients to adverse health outcomes, thereby warranting proactive and structured management strategies. HrHUA encompasses presentations complicated by gout or monosodium urate (MSU) crystal deposition; renal involvement, including nephrolithiasis or chronic kidney disease (CKD); cardiovascular disorders, such as hypertension, coronary artery disease (CAD), chronic heart failure (CHF), myocardial infarction, or atrial fibrillation; metabolic disturbances including type 2 diabetes mellitus (T2DM), obesity, metabolic syndrome (MetS), dyslipidemia, or non-alcoholic fatty liver disease (NAFLD); as well as neurological sequelae such as stroke (II-III, Strong recommendation). Key points: All patients with HUA should undergo a comprehensive evaluation incorporating clinical history, physical examination, and relevant laboratory and imaging assessments to identify prognostic risk factors related to HUA-associated organ involvement. Clinical question 2: Should ULT be recommended for HUA patients with gout? Consensus 2.1: For patients with gout attacks ≥2 times per year, initiation of ULT is recommended (II, Strong recommendation). Consensus 2.2: For patients with gout attacks in total ≥2 times, but ≤1 time per year, initiation of ULT may be considered (II, Weak recommendation). Consensus 2.3: For patients with a single gout attack accompanied by CKD stage G3 or higher, SUA >540 μmol/L (9.0 mg/dL), or nephrolithiasis, ULT may be considered (II–V, Weak recommendation). Consensus 2.4: For patients presenting with gouty tophi or imaging evidence of gout-related joint damage, initiation of ULT is recommended (II, Strong recommendation). Key points: Patients with severe renal impairment should not receive uricosuric agents. If target SUA levels cannot be achieved with monotherapy, combination therapy with agents of complementary mechanisms may be considered. Initiation of ULT is reasonable during the intercritical period of gout, whereas in acute flares, ULT should only be initiated after adequate anti-inflammatory control has been established. Clinical question 3: Should ULT be recommended for HUA patients with nephrolithiasis? Consensus 3: For HrHUA patients with a history of nephrolithiasis, ULT may be considered to reduce the recurrence of nephrolithiasis (II, Weak recommendation). Key points: Xanthine oxidase inhibitors (allopurinol, febuxostat) are preferred in HrHUA patients with nephrolithiasis. Clinical question 4: Should ULT be recommended for HUA patients with CKD? Consensus 4: For HrHUA patients with CKD G3–4, ULT may be considered to slow the decline of renal function, reduce the risk of gout flares, and lower the risk of cardiovascular events (I–II, Weak recommendation). Key points: For HrHUA patients with CKD G3 or higher receiving ULT, dose adjustment of associated agents should be made according to estimated glomerular filtration rate (eGFR). Clinical question 5: Should ULT be recommended for HUA patients with hypertension? Consensus 5: For HrHUA patients accompanied by hypertension, initiation of ULT may be considered for cardiovascular protection (Ⅱ, Weak recommendation). Key points: Antihypertensive therapy should preferentially include agents with uricosuric effects, such as angiotensin II receptor blockers (ARBs: losartan, irbesartan, olmesartan) and calcium channel blockers (amlodipine, nifedipine). Thiazide (hydrochlorothiazide) and loop diuretics (furosemide, torsemide) should be avoided whenever possible. Clinical question 6: Should ULT be recommended for HUA patients with CAD? Consensus 6: For HrHUA patients complicated by CAD who require percutaneous coronary intervention (PCI), initiation of ULT may be considered to protect renal function (Ⅱ, Weak recommendation). Key points: Cardiovascular medications with uric acid-lowering effects, such as atorvastatin and simvastatin, are preferred. Low-dose aspirin (≤325 mg/day) may slightly increase SUA levels; however, if antiplatelet therapy is clinically required and no suitable alternative is available, it may be continued with caution. Ticagrelor should be avoided whenever possible. Clinical question 7: Should ULT be recommended for HUA patients with CHF? Consensus 7: For HrHUA patients accompanied by CHF, initiation of ULT may be considered to improve cardiac function and reduce all-cause mortality risk (I–III, Weak recommendation). Key points: For the management of heart failure, preference should be given to cardiovascular agents with uric acid–lowering effects, such as angiotensin receptor–neprilysin inhibitors (ARNIs: sacubitril/valsartan) and sodium-glucose cotransporter-2 inhibitors (SGLT2i: dapagliflozin, empagliflozin). When alternatives are available, thiazide and loop diuretics should be avoided. Clinical question 8: Should ULT be recommended for HUA patients with T2DM? Consensus 8: For HrHUA patients accompanied by T2DM, initiation of ULT may be considered to improve insulin resistance, preserve renal function, and reduce the risks of all-cause, cardiovascular, and non-cardiovascular mortality (II–III, Weak recommendation). Key points: For glucose-lowering therapy, agents with uric acid-lowering properties, such as SGLT2i (e.g., dapagliflozin and empagliflozin) and insulin sensitizers such as pioglitazone, should be preferred. Clinical question 9: Should ULT be recommended for HUA patients with stroke? Consensus 9: For HrHUA patients accompanied by stroke, initiation of ULT may be considered to improve vascular and neurological functional status (II, Weak recommendation). Key points: Cardiovascular medications with urate-lowering effects, such as atorvastatin or simvastatin, are preferred when clinically appropriate. Although low-dose aspirin may slightly increase SUA levels, its established antiplatelet benefits usually outweigh its modest effect on SUA levels; therefore, continuation is warranted when indicated. Clinical question 10: What are the optimal timing and treatment targets for initiating ULT? Consensus 10.1: For HrHUA patients with gout who meet the criteria for ULT, ULT should be initiated immediately upon diagnosis, with a target SUA level of ≤360 μmol/L (6.0 mg/dL) (II, Strong recommendation). Consensus 10.2: For gout patients with tophi, chronic gouty arthritis, or frequent gout flares, SUA target should be maintained at ≤300 μmol/L (5.0 mg/dL) (III, Weak recommendation). Consensus 10.3: For HrHUA patients with nephrolithiasis, CKD G3–4, hypertension, CAD requiring PCI, CHF, T2DM, or stroke, lifestyle intervention should be initiated and strictly followed; if SUA remains >480 μmol/L (8.0 mg/dL) after 6 months of lifestyle intervention, ULT should be initiated, with a target of SUA ≤360 μmol/L (GPS, Expert consensus). Consensus 10.4: For all HUA patients, over-lowering of SUA to <180 μmol/L (3.0 mg/dL) should be avoided (GPS, Expert consensus). Consensus 10.5: Lifestyle intervention, including dietary purine restriction, limitation of alcohol and fructose intake, and weight reduction when appropriate, should be implemented and documented as foundational management for all patients with HrHUA (GPS, Expert consensus). Clinical question 11: How to prevent acute gout flares during ULT initiation? Consensus 11.1: When initiating ULT in HrHUA patients, the potential risk of inducing acute gout flares should be considered (GPS, Expert consensus). Consensus 11.2: When initiating ULT in gout, prophylactic anti-inflammatory therapy (low-dose colchicine, non-steroidal anti-inflammatory drugs, or corticosteroids) for 3–6 months is recommended to reduce the risk of gout flares (II–III, Strong recommendation). Consensus 11.3: Initiating urate-lowering agents at a low dose and gradually titrating upward can further reduce the risk of flare induction (II, Weak recommendation). Academic supervisors Hejian Zou (Huashan Hospital, Fudan University), Yan Zhao (Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences), Zhuoli Zhang (Peking University First Hospital; National Clinical Research Center for Skin and Immune Diseases), Lie Dai (Sun Yat-sen Memorial Hospital, Sun Yat-sen University). Writing experts Xiaoxia Zhu (Huashan Hospital, Fudan University), Yingqian Mo (Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University), Lihua Duan (Jiangxi Provincial People’s Hospital), Yufeng Qing (The Affiliated Hospital of North Sichuan Medical College). Expert committee (in alphabetical order by surname) Lie Dai (Sun Yat-sen Memorial Hospital, Sun Yat-sen University), Lingli Dong (Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology), Lihua Duan (Jiangxi Provincial People’s Hospital), Fei Gao (Fuzhou University Affiliated Provincial Hospital), Lan He (The First Affiliated Hospital of Xi’an Jiaotong University), Jingchun Jin (The Affiliated Hospital of Yanbian University (Yanbian Hospital)), Yinghui Jin (Center for Evidence-Based and Translational Medicine, Wuhan University), Qin Li (The First People’s Hospital of Yunnan Province), Xiaomei Li (The First Affiliated Hospital of the University of Science and Technology of China), Jin Lin (The First Affiliated Hospital of Zhejiang University School of Medicine), Shudian Lin (Hainan General Hospital), Shunping Lin (Union Hospital, Fujian Medical University), Yingqian Mo (Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University), Yunfeng Pan (The Third Affiliated Hospital, Sun Yat-sen University), Yufeng Qing (The Affiliated Hospital of North Sichuan Medical College), Haili Shen (The Second Hospital of Lanzhou University), Xiaofei Shi (The First Affiliated Hospital of Henan University of Science and Technology), Juan Su (Qinghai University Affiliated Hospital), Wenfeng Tan (The First Affiliated Hospital of Nanjing Medical University), Caihong Wang (The Second Hospital of Shanxi Medical University), Youlian Wang (Jiangxi Provincial People’s Hospital), Yu Wang (Peking University First Hospital), Yukai Wang (Shantou Central Hospital), Wei Wei (Tianjin Medical University General Hospital), Huaxiang Wu (The Second Affiliated Hospital of Zhejiang University School of Medicine), Husheng Wu (Beijing Jishuitan Hospital, Capital Medical University), Qibing Xie (West China Hospital, Sichuan University), Pingting Yang (The First Affiliated Hospital of China Medical University), Fengxiao Zhang (The First Hospital of Hebei Medical University), Miaojia Zhang (The First Affiliated Hospital of Nanjing Medical University), Zhuoli Zhang (Peking University First Hospital; National Clinical Research Center for Skin and Immune Diseases), Dongbao Zhao (Shanghai Changhai Hospital, Naval Medical University), Yan Zhao (Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences), Yanping Zhao (The First Affiliated Hospital of Harbin Medical University), Xiaoxia Zhu (Huashan Hospital, Fudan University), Hejian Zou (Huashan Hospital, Fudan University), Xiaoxia Zuo (Xiangya Hospital, Central South University). Methodology expert Yinghui Jin (Center for Evidence-Based and Translational Medicine, Wuhan University). Funding This work was supported by the Shanghai Hospital Development Center (Grant No. SHDC2020CR1013B). The views expressed in this article are solely those of the authors and do not necessarily reflect the positions of their affiliated institutions or the funding body. Conflicts of interest None.