2024 中国指南：高尿酸血症与痛风的诊断和治疗（更新版）-第1部分（英文版）

2024 Update of Chinese Guidelines for Diagnosis and Treatment of Hyperuricemia and Gout Part I:

Mingshu Sun ${}^{1}$ | Zhaohui Lyu ${}^{2}$ | Can Wang ${}^{3}$ | Yan Li ${}^{4}$ | Dongbao Zhao ${}^{5}$ | Xingwu Ran ${}^{6}$ | Haibing Chen ${}^{7}$ | ${}^{6}$ | Benli Su ${}^{8}$ |Xiangyun Chang ${}^{9}$ | Ping Liu ${}^{10}$ | Dewen Yan ${}^{11}$ | Xiuyun Jiang ${}^{12}$ | Kang Chen ${}^{2}$ | Jiaqing Shao ${}^{13}$ | Xiaochun Teng ${}^{14}$ |Yongli Yao ${}^{15}$ | Yuming Li ${}^{16}$ | Ying Chen ${}^{3}$ | Jidong Cheng ${}^{17}$ | Zhifeng Cheng ${}^{18}$ | Zhen Liu ${}^{3}$ | Fengjing Liu ${}^{19}$ |Xinyu Li ${}^{20}$ | Huiyong Yin ${}^{21}$ ${}^{(i)}$ | Chao Liu ${}^{22}$ ${}^{(i)}$ | Hsiao-Yi Lin ${}^{23}$ | Yaolong Chen ${}^{24}$ ${}^{(i)}$ | Wen-Chan Tsai ${}^{25}$ | Ronald M. L. Yip ${}^{26}$ |Changgui Li ${}^{17}$ | Jiajun Zhao ${}^{12}$ |

'Depranology, Xiang'an Hospital of Xiamen University, Xiamen, China| 2Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing, China| 3Department of Metabolism, the Affiliated Hospital of Qingdao University, Qingdao, China| 4Department of Endocrinology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,China| 5Department of Rheumatology, the First Affiliated Hospital of Naval Medical University(Shanghai Shanghai Hospital), Shanghai, China| 6Department of Endocrinology, West China Hospital, Sichuan University,Chengdu,China| 7Department of Endocrinology and Metabolism, Shanghai Senthers Pople's Hospital, Tongji University School of Medicine, Shanghai,China| 8Department of Endocrinology and Metabolism, Second Hospital of Dalian Medical University, Dalian, China| 9Department of Endocrinology,the First Affiliated Hospital of Shihezi University, Xinjiang, China| 10Department of Endocrinology, School of Medicine, the Second Affiliated Hospital,The Chinese University of Hong Kong, Shenzhen& Longang District People's Hospital of Shenzhen, Shenzhen, China| 12Department of Endocrinology, Shandong Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen, Shenzhen, China| 12Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China| 13Department of Endocrinology, Affiliated Ling Hospital, Medical School of Nanjing University, Nanjing, China| 14Department of Endocrinology and Metabolism, the First Hospital of China Medical University, Shenyang,China| 15Department of Endocrinology, Qinghai Provincial People's Hospital's Xinghi, China| 16Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology(HUST), Wuhan, China| 17Department of Endocrinology, Xiang'an Hospital of Xiamen University,Xiamen,China| 18Department of Endocrinology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China| 19Department of Endocrinology, Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China| 20Department of Endocrinology, Central Hospital of Dalian University of Technology(Dalian Municipal Central Hospital), Dalian, China| 21Department of Biomedical Sciences,City University of Hong Kong, Hong Kong, China| 22Department of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China| 23Division of Allergy Immunology and Rheumatology, Cheng-Hsin General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan| 24Research Unit of Evidence-Based Evaluation and Guidelines, Chinese Academy of Medical Sciences(2021RU017), School of Basic Medical Sciences, Lanzhou University, Lanzhou, China| 25Department of Rheumatology, Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan| 26Tung Wah Group of Hospitals Integrated Diagnostic and Medical Centre, Kwong Wah Hospital, Kowloon, China

Correspondence: Changgui Li(changguili@vip.163.com)| Jiajun Zhao(jzhao@sdu.edu.cn)

Received: 7 May 2025| Revised: 6 July 2025| Accepted: 14 July 2025

Funding: This work was supported by National Key Research and Development Program of China(Grants 2022YFC2503300 and 2022YFE0107600) and Projects of International Cooperation and Exchanges NSFC(Grant 82220108015).

Keywords: diagnosis| gout| guideline| hyperuricemia| management| prediction

ABSTRACT

Background: In 2018, the Chinese Society of Endocrinology developed the“Chinese guideline for diagnosis and treatment of hyperuricemia and gout(2019)”. Over the past 5 years, clinical and experimental research has expanded our knowledge of gout,

resulting in novel diagnostic and therapeutic approaches. This update, prompted by new clinical challenges and gaps in evidence,aims to refine the 2019 guidelines.

Methods: The working group formulated clinical questions based on a nationwide questionnaire survey, and the expert panel evaluated new evidence addressing these questions from January 2019 to March 2025. The guideline development followed the Grading of Recommendations Assessment, Development, and Evaluation(GRADE) approach, adhering to internationally recog-nized protocols for clinical practice guideline development.

Results: The update includes 26 recommendations addressing 10 clinical questions related to urate-lowering therapy(ULT) for asymptomatic hyperuricemia and reproductive populations, anti-inflammatory treatments, urine alkalinization, dietary advice,and gout diagnosis in patients without a record of hyperuricemia and gout flare predictions in patients with asymptomatic hype-ruricemia and intermittent gout. It recommends feubostasat as a first-line ULT for asymptomatic hyperuricemia and using it with caution during pregnancy and lactation. ULT should be customized according to the pathophysiologic type of hyperuricemia.Chronic gout management includes maintaining serum urate levels between 180 and 300μmol/L and prolonged glucocorticoid tapering in combination with colchicine. Alkalinization with citrate is preferred over sodium bicarbonate for patients with urine pH<6.0. Novel biomarkers for predicting gout flares are proposed for high-risk populations.

Conclusions: These updated guidelines incorporate expert consensus and evidence to provide refined strategies for the diagno-sis, prevention, and treatment of hyperuricemia and gout.

1| Introduction

Gout is a prevalent inflammatory metabolic dysfunctional dis-lease induced by the deposition of monosodium urate(MSU)crystals in joints and soft tissues. Hyperuricemia, defined by elevated concentration of serum urate(SU) exceeding the sat-uration threshold of 420μmol/L(7mg/dL), is a primary risk factor for the development of gout. The treatment paradigm includes long-term urate-lowering therapy(ULT) to reduce SU levels, dissolve MSU crystals, and prevent and manage recur-rent flares. However, recent data indicate an increase in both the prevalence and burden of gout globally.

Gout management involves several disciplines in China, like rheu-matology, endocrinology, nephrology, and general internal medi-cine. By following national standardized procedures and protocols for the development of clinical evidence-based guidelines[1,2], the Chinese Society of Endocrinology, Chinese Medical Association launched in 2018 and accomplished with multidisciplinary ex-perts the Chinese Guidelines for Diagnosis and Treatment of Hyperuricemia and Gout(2019)(2019 Guideline). The 2019 Guideline developed a series of recommendations, especially on stratified gout diagnosis and ULT for asymptomatic hyperurice-mia and gout, and considerations for pathophysiologic type-guided ULT and urine alkalization[3]. The guideline was widely adopted.However, evidence supporting several recommendations was not so strong, and several clinical problems prompted then were not included due to insufficient evidence.

During the past 5 years, emerging studies revealed new devel-opments in gout management. Recent national/regional guide-lines,including the 2021 Asia-Pacific League of Associations for Rheumatology(APLAR)[4] and the 2023 Hong Kong Society of Rheumatology(HKSR)[5] guidelines, have provided some of the advances. Others, such as evidence concerning adjunctive therapies and prediction biomarkers of gout flares, do not arouse sufficient attention[6, 7]. The evolving body of research neces-sitated an update of the 2019 guidelines. The Chinese Society of Endocrinology initiated this 2024 Update of Chinese Guidelines for Diagnosis and Treatment of Hyperuricemia and Gout(2024

Update), aiming to provide refined evidence-based recommen-dations, considering emerging therapies, diagnostic tools, and clinical insights.

2| Methods

The 2024 Update was developed following the Grading of Recommendations Assessment, Development and Evaluation(GRADE) methodology, incorporating evidence from system-atic literature reviews SLRs), standardized evidence quality assessment, and expert consensus, supported by the Lanzhou University GRADE Center. Based on the evidence quality clas-sification(A, B, C, and D)(Table S1), and considering other fac-tors such as cost, accessibility, and the balance of benefits and harms, we form the strength of recommendations. The grade of recommendations is determined as grade 1, recommend to or not to use, and grade 2, suggested to or not to use(Table S2).

A guidance steering committee of five senior specialists was es-tablished to oversee the processing of the guideline. A multidisci-plinary expert panel(EP) was assembled with experts in clinical practice and research of gout from all over China, for clinical question proposals, approval for the suggestions and statements composition, including 20 endocrinologists, 12 rheumatologists,7 experts in nephrology, gastroenterology, and cardiology, and 2 methodologists. A working group of 11 junior endocrinologists was also organized to implement the process of guideline development.

Clinical questions were proposed through a review of guidelines and expert consensus published since 2019, and a national ques-tionnaire survey.The EP discussed at the first face-to-face meeting,incorporating clinical evidence and physicians' input, finalized 10 key questions for the 2024 Update, which were deconstructed using the Patient/Population,Intervention,Comparison,Outcome(PICO) principle(Table S3). A second questionnaire among the EP ranked outcome indicators by importance(Table S4).

Evidence retrieval was developed among China Biomedical Literature Database, CNKI, Wanfang, VIP, PubMed, Web of

TABLE 1| Ten clinical questions and the literature distribution of each evidence body.

|Questions|Systematic review/ meta analysis|Distribution of evidence (chapter)||| |---|---|---|---|---| |Questions|Systematic review/ meta analysis|Original research|Guidelines/consensus|| |Urate-lowering therapy in asymptomatic hyperuricemia|4 Meta analyses Systematic reviews|3 RCTs 2 Cohort studies|1 Guideline 3 Consensus|0| |Urate-lowering therapy guided by renal urate excretion|0|2 RCTs 1 Cohort studies|2 Guidelines 1 Consensus|0| |Anti-inflammatory therapy with glucocorticoids for recurrent gout|2 Meta analyses 3 Systematic reviews|4 RCTs|3 Guidelines 2 Consensuses|1 Book| |Management for chronic gouty arthritis|1 Systematic review|0|3 Guidelines 1 Consensus|0| |Urine alkalization|1 Meta analysis 1 Systematic review|3 RCTs 1 Cross-sectional study 1 Cohort study|0|0| |Dietary management|2 Meta analyses Systematic reviews|3 RCTs 3 Cross-sectional studies 2 Case-Control studies 2 Cohort studies|0|0| |Gout management in women of reproductive period|0|1 Cross-sectional study 4 Case reports|2 Guidelines 2 Consensuses|0| |Gout management in men of reproductive period|1 Meta analyses|2 Cohort studies 1 Case report|2 Guidelines|0| |Diagnosis of normouricemic gout|1 Meta analysis 1 Systematic review|1 RCT 1 Cohort study|3 Guidelines|0| |Assessment of gout flare risk|1 Systematic review|5 Cohort studies 5 Case-Control studies|0|0|

Abbreviation: RCT, randomized controlled trial.

Science, Cochrane Library,Embase,and guideline databases for studies published between January 2019 and January 2024.Prior to the publication of the guidelines(March 1,2025), the evidence panel performed a rapid evidence review across all relevant questions to prevent oversight of the most recent evidence.

A total of 40 guidelines/consensus and 505 articles were re-trieved. After removing duplicates and articles not within the scope of the clinical questions, 17 systematic reviews, 50 original studies, and 24 previous guidelines/consensus were included,forming the evidence base for the recommendations.

The preliminary results of the SLRs were presented to EP members during the second face-to-face meeting. The recom-mendations were drafted a revised in two meetings and two rounds of Delphi voting. A 10-point Likert scale was used to rate agreement, with consensus achieved when over 80% of the EP members rated a recommendation≥ 7. In very few cases, a good practice statement(GPS) may be used, representing the opin-ions of the EP members. One patient representative was invited to comment on the recommendations. The final version of the

recommendations will be distributed through publications, aca-demic meetings, and so forth.

The overall procedure is summarized in the flow chart(Figure S1). This guideline was registered(IPGRP, http://www.guide lines-registry.org)(PREPARE-2024CN563).

3| Results

The PICO questions and the corresponding evidences were pre-sented to the EP(Table 1).Finally,25 recommendations reached consensus(Table 2, Figure 1).

3.1| Urate-Lowering Therapy in Asymptomatic Hyperuricemia

For patients with asymptomatic hyperuricemia, first-line ULT options include febuxostat,alloporinol, and benzbromarone;long-term ULT is generally recommended, with discontinuation considered for patients maintaining SU≤360μmol/L for three

TABLE 2| Recommendations with grades(GoR), levels of evidence( LoE), and levels of agreement( LoA).

||PICO question|GoR|LoE|LoA (%)| |---|---|---|---|---| |Urate-lowering therapy in asymptomatic hyperuricemia||||| |1. For patients with asymptomatic hyperuricemia, first-line ULT options include febuxostat, allopurinol and benzbromarone|1|1|A|95.2| |2. Long-term ULT is generally recommended, with discontinuation considered for patients maintaining SU ≤360μmol/L for three months or<240μmol/L on two separate occasions. The decision should involve lifestyle modification and regular SU monitoring|2|GPS||88.7| |Urate-lowering therapy guided by renal urate excretion||||| |3.The classification of hyperuricemia, based on 24-h renal urate excretion (UUE) and fractional excretion of renal urate (FEUA), is recommended to guide ULT selection|3|2|C|91.9| |4.For renal underexcretion, benzbromarone is the preferred agent|3|2|C|93.5| |5.For combined hyperuricemia (UUE between 600 and 700mg), low dose febuxostat and an add-on low dose benzbromarone if necessary are suggested|3|2|C|96.8| |Anti-inflammatory therapy with glucocorticoids for recurrent got||||| |6. For recurrent gout, glucocorticoids are suggested to be tapered down slowly,generally within one month|10|2|D|98.4| |7. Colchicine is recommended to prevent flares during glucocorticoid tapering|10|2|B|96.8| |8. IL-1 inhibitors are suggested for patients unresponsive to conventional therapies|10|2|B|100| |Management for chronic gouty arthritis||||| |9. For chronic gouty arthritis, ULT should aim to maintain SU levels between 180 and 300μmol/L|11|1|C|98.4| |10. Flare prophylaxis is suggested to continue for at least 3 months after achieving target SU levels if there is no evidence of tophi|11|2|C|100| |11. If tophi present, prophylaxis is suggested to continue for at least 6 months after achieving target SU levels and the dissolution of tophi|11|2|C|100| |Auxiliary therapy: Urine alkalization||||| |12. Urine alkalization is suggested for patients with hyperuricemia and gout, particularly those with a morning urine pH< 6.0 and taking uricosuric agents|4|2|C|98.4| |13. Citrate preparations are preferred; Sodium bicarbonate is an alternative for patients who cannot tolerate citrate or have renal impairment|4|2|C|98.4| |14. The dosage of alkalization agents should be adjusted to maintain morning urine pH levels between 6.2 and 6.9|4|2|C|98.4| |Auxiliary therapy: Dietary management||||| |15. Dietary restrictions on high-purine foods, high-fructose products, and alcohol are recommended|5|2|B|98.4| |16. While dietary fiber, tart cherry products, citric acid products, and skim milk are encouraged|5|2|C|100| |Gout management in women of reproductive period||||| |17. Lifestyle interventions should be prioritized. Benzbromarone and allopurinol|6|2|D|98.4| |are contraindicated during pregnancy, while febuxostat can be used cautiously. Allopurinol can be used during lactation|||||

(Continues)

||PICO question|GoR|LoE|LoA (%)| |---|---|---|---|---| |Recommendations||||| |18. Low-dose glucocorticoids, colchicine, and nonsteroidal anti-inflammatory drugs(NSAIDs) are acceptable for managing gout flares|8|2|D|98.4| |Gout management in men of reproductive period||||| |19. For men planning conception, discontinuation of alloporinol and febuxostat is recommended for at least 3 months in those with suspected infertility during treatment. Benzbromarone is recommended if necessary|7|2|D|93.5| |20. Low-dose glucocorticoids, colchicine, and NSAIDs are suggested for managing gout during this period|9|2|D|93.5| |Diagnosis normouricemic gout||||| |21. The presence of MSU crystals in synovial fluid is recommended as the gold standard for diagnosing gout in patients with normouricemia|12|1|C|100| |22. For those who cannot undergo joint aspiration or have negative results, alternative diagnostic tools such as ultrasound, dual-energy CT(DECT), and X-ray are recommended to detect MSU crystal deposits|12|2|B|100| |23. Repeated SU assessment two weeks after a joint episode is recommended to obtain the authentic SU level to follow the 2015 ACR/EULAR diagnostic criteria|12|2|B|100| |Assessment of gout flare risk||||| |24. Imaging techniques such as ultrasound and DECT, are suggested to be used to assess flare risk in patients with gout or asymptomatic hyperuricemia|13|2|B|98.4| |25. Biomarkers like baseline SU, are suggested to be used to assess flare risk in patients with gout or asymptomatic hyperuricemia|13|2|C|96.8|

Abbreviations:ACR,American College of Rheumatology;DECT,dual-energy CT;EULAR,European Alliance of Associations for Rheumatology;FEUA,fractional excretion of uric acid; GPS,good practice statement; IL-1,interieukin-1; MSU,monosodium urate; NSAIDs, nonsteroidal anti-inflammatory drugs; PICO,population,invention,comparison,outcome;SU,serum urate;ULT,urate-lowering therapy;UUE,urinary urate excretion.

months or<240μmol/L on two separate occasions. The decision should involve lifestyle modification and regular SU monitoring.

Patients with asymptomatic hyperuricemia and SU≥9mg/dL, or those with comorbidities such as cardiovascular, metabolic dys-function, and kidney diseases, should initiate ULT as per the 2019 Guideline[3]. Febuxostat is either comparable to or more effective than alloporinol in terms of urate-lowering efficacy[8, 9], and is safer in patients with severe chronic kidney disease(CKD)[10].In patients with CKD stage 3a and asymptomatic hyperuricemia,febuxostat provides better renal protection than benzbromarone[10]. Although feubostat has received a boxed warning from the U.S. Food and Drug Administration for increased risk of mortal-ity in patients with cardiovascular comorbidities following the CARES trial, a recent global meta-analysis did not show signif-icant differences in cardiovascular outcomes between feubostat(40 or 80mg per day) and allopurinol(200-300mg per day)[8].Furthermore, Asians have a higher risk of allergic reaction to al-lopurinol due to the prevalence of HLA-B*5801, which may affect the risk-benefit ratio in the Chinese population.

Allopurinol is recommended by guidelines in many countries as a first-line treatment in patients with asymptomatic hyper-uricemia. Compared to allopurinol, benzbromarone may re-duce the risk of dialysis by approximately 50% in patients with asymptomatic hyperuricemia and CKD. Benzbromarone has urate-lowering effects similar to those of febuxostat[11], and is

particularly effective in patients with poor renal urate excretion[11]. Therefore, both allopurinol and benzbromarone are recom-mended as first-line treatment.

Currently, there is insufficient evidence to support discontinu-ing medication in patients with asymptomatic hyperuricemia.A small subset of patients may be able to maintain SU levels below 360μmol/L through, exercise, and management of metabolic syndrome. Meta-analyses suggest that excessively low SU levels are associated with an increased risk of neurodegen-erative diseases. Therefore, we suggest that patients on low-dose urate-lowering agents who maintain SU levels≤360μmol/L for 3 months or achieve SU levels below 240μmol/L on at least two sep-arate occasions may consider discontinuing ULT, provided they maintain a healthy lifestyle and regularly monitor their SU levels.

3.2| Urate-Lowering Therapy Guided by Renal Urate Excretion

The classification of hyperuricemia, based on 24-h urinary urate excretion(UUE) and fractional excretion of renal urate(FEUA),is recommended to guide ULT selection; for renal underexcre-tion, benzbromarone is the preferred agent, while for combined hyperuricemia(UUE between 600 and 700 mg), low-dose febux-ostat and an add-on low-dose benzbromarone if necessary are suggested.

 FIGURE1| Summary of the recommendations on management of patients with asymptomatic hyperuricemia and gout. 2019 Guideline, Guideline for the Diagnosis and Treatment of Hyperuricemia and Gout in China(2019). Chinese Journal of Endocrinology and Metabolism. 2020;36(1):13.https://rsyigle.com/cmaid/1179377;*,comorbidities including hypertension, dyslipidemia, diabetes, obesity, stroke, coronary heart disease, heart failure, uric acid nephrolithiasis, chronic kidney disease(CKD≥ stage 2);#, conditions including gout flare≥2 times/year, tophi, chronic gouty ar-thritis, nephrolithiasis, chronic kidney disease, hypertension, diabetes, dyslipidemia, stroke, ischemic heart disease, heart failure, and gout onset age<40 years old; AHU,asymptomatic hyperuricemia;FBX,febuxostat;GCs,glucocorticoids;IL,interleukin;NSAIDs,non-steroidal anti-inflammatory drugs; ROL, renal overload;RUE,renal underexcretion;SU,serum urate;ULT,urate-lowering therapy;XOIs,xanthin oxidase inhibitors.

The 2019 Guideline clarified that hyperuricemia classification should be determined based on a combination of baseline UUE and FE_{UA}[3]. The 2016 European Alliance of Associations for Rheumatology(EULAR) guideline recommended assessing renal ature excretion prior to initiating ULT in gout patients with early onset or a family history of early onset to guide med-ication selection[12].

A randomized controlled trial(RCT) conducted in Chinese gout patients with renal urate underexcretion found that benzborromar(25 mg/day) was more effective than febux-ostat(20mg/day) in achieving SU target levels, with fewer

occurrences of abnormal liver function[11]. A cohort study conducted over 3 months showed that benzbromarone(25 mg/day) led to a higher SU target achievement rate in patients with renal underexcretion compared to unclassified patients[13]. However, it should be avoided in patients with UUE>700 mg on a low-purine diet or>800 mg on a regular diet,which indicate a dominant renal urate overload due to the possibility of renal damage[14]. A RCT study demonstrated that adding benzbromarone(25 mg/day) to febuxostat(20 mg/day) achieved superior urate-lowering efficacy compared to febuxostat monotherapy in gout with combined hyperurice-mia over three months[15].

3.3| Anti-Inflammatory Therapy With Glucocorticoids for Recurrent Gout

Glucocorticoids initiated for recurrent got flare are suggested to be tapered down slowly, generally within 1 month; Colchicine is recommended to prevent flares during glucocorticoid taper-ing; IL-1 inhibitors are suggested for patients unresponsive to conventional therapies.

Systemic or intra-articular glucocorticoids have been proved and suggested by previous guidelines for short-term use in gout flares[5,16-18]. For patients with recurrent gout(≥2 episodes per year),particularly those experiencing flares within 3 months after the last episode, or those not receiving prophylactic treatment during ULT, the tapering period may be extended to 14 or even 21 days,accompanying a low dose of colcicine. However, the total course of glucocorticoids therapy should adhere to the"Guidelines for Clinical Application of Glucocorticoid Drugs(2023 Edition)",which generally limits short-term use to 1 month.

The 2020 American College of Rheumatology(ACR) guide-lines for gout management conditionally recommend IL-1 inhibitors for patients who are unresponsive or intolerant to conventional anti-inflammatory therapy[2]. Anakinra was shown to be not superior to a single dose of triamcinolone(40 mg injection) when administered at 100 or 200 mg/day for 5 days. Rilonacept showed comparable efficacy to indometh-acin when administered as a 320 mg subcutaneous injection.Canakinumab significantly alleviated pain and inflammation and reduced the risk of flares in patients with acute gouty ar-thritis with a single 150 mg dose. Recently, an express letter reported that firsekibart, a fully humanized IL-1β inhibitor administered as a single 200 mg subcutaneous injection, com-pared with compound betamethasone, demonstrated non-inferior pain relief for acute gout attack and superior efficacy in delaying new flares within 6 months among Chinese pa-tients[19]. Current evidence suggests that IL-1 inhibitors are effective and safe for patients with gout flares who are unsuit-able for standard therapies[20].

3.4| Management for Chronic Gouty Arthritis

For chronic gouty arthritis, ULT should aim to maintain SU lev-els between 180 and 300μmol/L; flare prophylaxis is suggested to continue for at least 3 months after achieving target SU levels if there is no evidence of toophi; if tophi are present, prophylaxis is suggested to continue for at least 6 months after achieving tar-get SU levels and the dissolution of tophi.

The primary goal in managing chronic gout is to maintain SU at lower levels to promote the dissolution of crystals and, in some cases, tophi.The 2012 ACR guidelines for gout management rec-ommend maintaining SU level<6mg/dL for all gout patients,and<5mg/dL for those with tophi[21]. These targets were re-affirmed by the 2023 consensus recommendations of the Hong Kong Society of Rheumatology[5].

Guidelines also recommend low-dose colchicine, NSAIDs, or low-dose corticosteroids for gout flare prophylaxis for at least 3 months(for those without tophi) or at least 6 months(for those

with tophi), with the duration potentially extended based on the dissolution status of tophi[22, 23]. In chronic gout, maintaining a constant, safe level of SU is crucial to prevent recurrent crystal formation and inflammation. Therefore, the EP reached con-sensus that prophylaxis treatment should not be discontinued until the SU target is stable for 3-6 months, depending on the presence of tophi.

IL-1 inhibitors are a newer class of drugs for the treatment of acute gout. Some studies have explored the use of IL-1 inhibitors as prophylactic agents, showing promising results; however, in-fection must be ruled out before administration, particularly in chronic gouty arthritis.

3.5| Auxiliary Therapy: Urine Alkalization

Urine alkalization is suggested for patients with hyperuricemia and gout, particularly those with a morning urine pH<6.0 and taking uricosuric agents; citrate preparations are preferred; so-dium bicarbonate is an alternative for patients who cannot toler-ate citrate or have renal impairment; the dosage of alkalization agents should be adjusted to maintain morning urine pH levels between 6.2 and 6.9.

Excessively acidic urine is a key factor in the formation of uric acid stones. Urine alkalization can dissolve existing stones and prevent the formation of new ones[24]. A cross-sectional study found that those with a urine pH≤5.0 were at higher risk of renal damage[25]. A study has shown that alloporinol combined with citrate preparations significantly increased urine pH and FEUA,while effectively reducing SU levels. Therefore, urine alkalization is recommended for hyperuricemia and gout patients, especially those on uricuricas agents, when the morning urine pH is<6.0.

Citrate preparations have been found to be of comparable ef-ficacy on urine alkalization but more effective in reducing gout flares, hematuria, urine albumin-to-creatinine ratio(UACR), and kidney stones and in improving the serum lipid profile[6, 26, 27]. Prolonged sodium bicarbonate use may in-crease sodium load, which heightens the risk of hypertension and promotes urinary calcium excretion, potentially increasing the likelihood of calcium stone formation. In summary, citrate preparations are considered the preferred agents for urine alka-lization in patients with gout and asymptomatic hyperuricemia,while sodium bicarbonate should be used in cases of intolerance to citrate preparations or when renal impairment and metabolic acidosis are present.

The dosage of urine alkalization medications is primarily deter-mined by urine pH levels. The goal is to maintain a morning urine pH between 6.2 and 6.9, which helps reduce the risk of uric acid kidney stones and promotes their dissolution. The rec-ommended treatment duration is currently 3-6 months[6].

3.6| Auxiliary Therapy: Dietary Management

Dietary restrictions on high-purine foods, high-fructose products,and alcohol are recommended; while dietary fiber, tart cherry products,citric acid products,and skim milk are encouraged.

Excessive intake of purine-rich food or ingredients that interfere with purine metabolism(such as fructose) or urate excretion(such as alcohol) may lead to hyperuricemia, and a low-purine diet benefits the gout population in reducing sUA levels and car-diovascular-metabolic conditions, particularly in those with the urate overproduction phenotype[28]. Certain dietary patterns,such as the Mediterranean diet and DASH diet(the dietary pat-tern in Dietary Approaches to Stop Hypertension), are beneficial for patients with gout by improving hyperuricemia and meta-bolic syndrome. These diets are more beneficial compared to the western diet, which is characterized by high purine, fat, and calorie content[29, 30].

The consumption of carbohydrates, particularly fructose-containing soft drinks, can exacerbate metabolic diseases and further elevate SU levels. Alcohol metabolism produces lactic acid, which reduces renal clearance of uric acid and decreases its excretion[31]. Certain alcoholic beverages, such as beer, con-tain high levels of purines, which can directly elevate SU levels.Additionally, alcohol increases the release of purines within the body, which are subsequently metabolized into uric acid, lead-ing to elevated SU levels.

Dietary fiber helps support blood sugar control, improves in-sulin resistance, and promotes uric acid excretion[32]. Tart cherry preparations and citric acid products can alkalize urine, effectively reduce the frequency of gout flares, and lower SU levels[6, 33]. Population studies have also indicated that, compared to other protein sources, milk does not elevate SU levels[34].

3.7| Gout Management in Women of Reproductive Period

Lifestyle interventions should be prioritized. Benzbromarone and alloporinol are contraindicated during pregnancy, while febuxostat can be used cautiously. Alloporinol can be used during lactation. Low-dose glucocorticoids, colchicine, and non-steroidal anti-inflammatory drugs(NSAIDs) are acceptable for managing gout flares.

Hyperuricemia during pregnancy is associated with adverse outcomes. Due to the lack of established diagnostic criteria for hyperuricemia during pregnancy and lactation, unclear initia-tion of treatment and targets, and insufficient clinical evidence for urate-lowering medication for pregnant or lactating women,SU levels should primarily be managed through appropriate di-etary and lifestyle modifications to ensure the safety of the fetus and nursing infants.

A systemic review suggests that alloporinol use during preg-nancy may have teratogenic effects, especially during the first trimester[35]. Most guidelines recommend against the use of benzbromarone and alloporinol in pregnant women. Febuxostat may be considered only when the benefits outweigh the poten-tial risks of the fetus. A case report showed that oxypurinool, the active metabolite of alloporinol, was detectable with low con-centration in breast milk of a lactating woman taking 300 mg/day of alloporinol, and relatively low levels in the infant's plasma 2 h after breastfeeding, without adverse events after 6 weeks'

exposure[36]. The American Academy of Pediatrics considers alloporinol compatible with breastfeeding.

During gout flares, low-dose glucocorticoids, colchicine, and NSAIDs are generally considered safe and effective.

Overall, medication use during pregnancy and lactation should be carefully evaluated, weighing the risks and benefits, with consideration for the potential effects on both mother and infant.

3.8| Gout Management in Men of Reproductive Period

For men planning conception, discontinuation of allopurinol and febuxostat is recommended for at least 3 months in those with suspected infertility during treatment. Benzbromarone is recommended if necessary. Low-dose glucocorticoids, colchi-cine, and NSAIDs are suggested for managing gout during this period.

Recent studies have indicated that hyperuricemia negatively af-fects sex hormones, semen quality, and contributes to erectile dysfunction(ED), while the impact of urate-lowering drugs on male fertility and pregnancy outcomes remains unclear. One study reported temporary infertility in a patient treated with alloporinol, with sperm penetration test scores returning to nor-mal after discontinuation[35]. A cohort study found that febux-ostat may pose a higher risk of ED compared to alloporinol in male gout patients[37]. A prospective cohort study concerning the effects of alloporinol, febuxostat, and benzbromarone on sperm quality and sex hormones found that benzbromarone increased sperm concentration, while febuxostat exposure de-creased sperm motility at three months[38]. However, the de-cision of ULT discontinuance should be based on a balanced risk/benefit evaluation. The 2016 EULAR recommendations on antirheumatic drugs during pregnancy and lactation, as well as the 2020 ACR guidelines on reproductive health management for patients with rheumatic and musculoskeletal diseases, sug-gest that men can use low-dose NSAIDs, colchicine, and tumor necrosis factor inhibitors during the conception period[39].

3.9| Diagnosis of Mormouricemic Gout

The presence of MSU crystals in synovial fluid is recom-mended as the gold standard for diagnosing gout in patients with normouricemia. For those who cannot undergo joint as-piration or have negative results, alternative diagnostic tools such as ultrasound, dual-energy CT(DECT), and X-ray are recommended to detect MSU crystal deposits. Repeated SU assessment 2 weeks after a joint episode is recommended to obtain the authentic SU level to follow the 2015 ACR/EULAR diagnostic criteria.

Although elevated SU is a primary driver for MSU crystal for-mation and serves as an independent risk factor for gout flares,not all patients experience high SU levels during flare episodes.During got flares, SU levels tend to decrease temporarily[40].Therefore, for patients highly suspected of having gout, if their SU levels are normal during joint episodes, or do not meet the

diagnostic criterion, it is recommended to recheck the SU level at least 2 weeks after the episode resolve[41].

In any cases, the presence of MSU crystals in synovial fluid or tophi remains the gold standard for diagnosis, as recommended in both the 1977 American Rheumatism Association criteria and the 2015 ACR/EULAR classification criteria[42]. For pa-tients who cannot undergo joint aspiration or present negative results, newly developed technologies like DECT and ultraso-nography are alternative diagnostic tools for patients without a history of hyperuricemia[43].

3.10| Assessment of Gout Flare Risk

Imaging techniques such as ultrasound and DECT, along with biomarkers like baseline SU, are suggested to be used to assess flare risk in patients with gout or asymptomatic hyperuricemia.

Gout flares not only cause severe pain, but they have also been recently linked to significant cardiovascular and cerebrovascu-lar complications. Predicting and preventing flares in patients with intercritical gout or asymptomatic hyperuricemia is im-portant for both healthcare providers and patients. Studies have demonstrated that the presence of MSU crystal deposition, con-firmed via ultrasound and/or DECT, is a risk factor for flares within 1-2years[44, 45]. These imaging modalities can also forecast the frequency of flares in joints with MSU crystal depo-sition following the initiation of ULT[46]. A systematic review revealed a positive correlation between the volume of urate crys-tal deposits detected by DECT and the risk of future flares[45].

In recent years, biomarkers have been increasingly used to sup-port both the diagnosis and prediction of gout flares. Emerging biomarkers and multi-omics predictive models have shown po-tential in forecasting gout flares and frequent attacks[7, 47, 48].A prospective cohort study involving 193 gout patients identified serum cancer antigen(CA) 72-4 as an independent risk factor for gout flares[47]. A cohort study investigating patients with infre-quent or frequent gout, using mass spectrometry-based untargeted metabolomics, established a predictive model for frequent gout at-tacks[7]. Another cohort study also identified seven characteris-tic metabolic markers that distinguish gout from hyperuricemia using mass spectrometry[48]. However, these findings require further validation through multicenter and prospective studies.

4| Discussion

This 2024 Update strengthens and expands many of the rec-ommendations presented in the 2019 Guideline, integrating novel evidences, multidisciplinary expert consensus, and pa-tient perspectives. These recommendations focus on ULT for asymptomatic hyperuricemia and individuals in the reproduc-tive phase, ULT guided by renal urate excretion criteria, special anti-inflammatory treatment strategies, diagnosis for normouri-cemic gout, prediction of gout flares, urine alkalization, and di-etary modifications regarding SU levels and inflammation. By offering clear guidance on these previously ambiguous issues,the update provides optimized management options for gout and hyperuricemia patients, addressing issues not adequately

covered in national/regional clinical practice guidelines from APLAR,HKSR,and the Taiwan consensus[4,5,14].

The treating serum urate-to-target strategy has consistently been acknowledged as the principle of managing gout and asymptom-atic hyperuricemia at risk[1-3, 14]. The 2019 Guidelines have recommended stratified ULT targets based on disease burden factors such as tophoti, flare frequency, comorbidities, and age at onset[3]. The question of whether ULT should be discontinued in long-term patients who have achieved target SU levels has been a significant clinical concern. Given the absence of long-term safety data for these ULT agents[10], the 2024 Update sug-gests discontinuing drugs under certain conditions and focusing on lifestyle management, which is similar to another guideline regarding lifestyle behaviours[49].

The determination of the first-line urate-lowering agent remains another contentious issue. The selection of an appropriate drug depends on several factors, including the individual patient's urate-lowering response, potential adverse effects, co-existing medicines, and pharmacoeconomic considerations. In light of re-cent high-quality clinical trial data[8,9,13,15], the 2024 Update recommends benzromarone over XOIs in Chinese patients with renal urate underexcretion. For patients with combined hyper-uricemia, a combination of low-dose febuxostat and benzroma-rone is now preferred, rather than titrating febuxostat alone[14].This renal urate excretion profile-guided ULT is underpinned by a cohort study in which subtypes of renal urate handling have subtype-specific clinical and genetic features[50].

Reproductive safety related to ULT has not been adequately ad-dressed in prior guidelines. This updated guideline systemati-cally reviewed the use of urate-lowering medications in specific populations, including pregnant women, lactating women, and men preparing for conception. Given the importance of these clinical issues and the acceptable strength of the available evi-dence, recommendations on gout management during the repro-ductive period of men and women were presented in the 2024 Update. However, balancing between benefit and damage and lifestyle modification is fully emphasized.

Gout has been identified as a heterogeneous disease with fre-quent comorbidities, which was highlighted by the 2018 EULAR evidence-based recommendations for gout diagnosis[1]. In this Update, comorbid conditions are considered when assessing risk factors for gout flare and other related conditions. Additionally,the guidelines offer more precise and robust recommendations,regarding urine alkalization for individuals with hyperurice-mia and gout. The EP agreed that citrate preparations should be preferred for urine alkalization due to their efficacy, poten-tial kidney protective effects, and anti-inflammatory prop-erties[6, 25, 26]. Due to the same concern about the potential harm of gout flares, the Update also recommends a gout diag-nostic framework for patients without verified hyperuricemia.

The role of lifestyle factors in the development of hyperuricemia and gout is well-established. In addition to dietary limitations,the 2024 Update provides prioritized dietary recommendations with certain nutrients that recently proved to be beneficial for urate reduction and gout management. Based on evidence[6, 32, 33], the EP endorses the consumption of dietary fiber,

tart cherry products, citric acid, and skim milk, which may help manage gout and improve patient outcomes.

Compared to the 2019 Guidelines and other previously published recommendations, this 2024 Update incorporates a deeper un-derstanding of the disease and integrates the latest evidence,especially studies from the Chinese population, broadening its applicability in diverse clinical scenarios. However, certain recommendations remain based on limited research, which ne-cessitates ongoing investigation, especially regarding long-term cardiovascular and renal outcomes. Clinical questions involving gout with comorbidities will be addressed in part two of this guideline.

Author Contributions

Changgui Li conceived the idea and submitted the project with a contri-bution from Zhaohui Lyu to the Chinese Association of Endocrinology Executive Committee. Jiajun Zhao organized and chaired the meetings.Changgui Li was in charge of the whole process of the guideline devel-opment. Mingshu Sun wrote the manuscript with the help of Can Wang and Zhen Liu. Wen-Chan Tsai and Ronald M.L. Yip provided opinions as external reviewers. All authors have contributed to this work and have approved the final version of the manuscript.

Acknowledgments

We thank the administrative team, members of the Working Group for their help with the questionnaire surveys, data collection, literature searching, and evidence retrieving and organizing the face-to-face meetings:Lidan Ma,Xiaoyu Cheng,Tian Liu,Xufei Luo,Lingling Cui,Yuwei He,Xinde Li,Jie Lu,Fei Yan,Lin Han,Hui Zhang,Wenyan Sun,Aichang Ji, Han Qi,Xinmiao Xu, Wu thank Qiang Li, Feng Wei,Yi Zhang, Lizhen Lan, Qing Wang, Jun Zhu, Zhuo Li, Jixing Liang, Lin Liao,Hongli Lin,Chao Xie,Huanbai Xu,Zhengi Anel,Mina,Luo Sun,Jia Li,Zhenmei An, and Li Cong for their participation in the development of this guideline. We thank Ziyi Chen and Qion Fu for the wording of the whole manuscript. We thank Mr. Jianshan Wu for providing us with patients' perspectives on the recommendations.

Ethics Statement

This study does not involve human participants.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Supporting Information

Additional supporting information can be found online in the Supporting Information section.