Gout

Gouty arthritis, a prevalent inflammatory condition characterized by the deposition of monosodium urate crystals within joints, often results in debilitating pain and inflammation. Conventional therapeutic approaches, including nonsteroidal anti-inflammatory drugs, corticosteroids, and urate-lowering agents such as allopurinol and febuxostat, often have limitations such as adverse effects, drug interactions, and suboptimal patient compliance. This review presents a comprehensive overview of both established and emerging therapeutic strategies, developed between 2019 and 2024, for gouty arthritis; the review focuses on their mechanisms of action, efficacy, and safety profiles. Novel therapeutic approaches include pharmaceutical plant additives (e.g., Citrullus colocynthis, Atractylodes lancea), anti-inflammatory agents such as canakinumab and ozone therapy, and complementary therapies such as warm ginger compresses, Qingpeng ointment, and various lifestyle modifications. These strategies offer promising alternatives to conventional treatments by targeting uric acid metabolism, inflammatory pathways, and crystal formation, potentially reducing reliance on standard medications and minimizing adverse effects. Although therapies such as canakinumab have demonstrated significant efficacy in reducing gout flares, others such as polyphenol-rich foods offer favorable safety profiles. Further research, including large-scale clinical trials, is warranted to validate these findings and integrate these strategies into clinical practice to improve patient outcomes and quality of life.

ImportanceClinicians often approach urate-lowering therapy (ULT) cautiously in patients with gout and impaired kidney function because they are concerned about the risk of progression to severe or end-stage kidney disease. However, evidence from randomized clinical trials of this association remains inconclusive.ObjectiveTo evaluate the association between achieving target serum urate level with ULT and progression of chronic kidney disease (CKD) to severe or end-stage in patients with gout and impaired kidney function.Design, setting, and participantsThis was a cohort study using the target trial emulation approach using data from a general practice database (IQVIA Medical Research Database) for 2000 to 2023. Eligible patients were 40 to 89 years old and had gout and CKD stage 3. Data analyses were performed from November 2023 to September 2024.ExposuresLowering serum urate level to target level (Main outcomes and measuresSevere or end-stage kidney disease, determined by an estimated glomerular filtration rate of less than 30 mL/min/1.73 m2 on at least 2 occasions more than 90 days apart within 1 year, or at least 1 Read code (per the Refined Etiology, Anatomical Site, and Diagnosis classification) for CKD stages 4 or 5, hemodialysis, peritoneal dialysis, or kidney transplant. The prespecified noninferiority margin of the hazard ratio (HR) was set at 1.2, comparing those who achieved the target serum urate level with those who did not.ResultsAmong the 14 792 participants (mean [SD] age, 73.1 [9.5] years; 9215 men [62.3%] and 5577 women [37.7%]) with gout and with CKD stage 3, the 5-year risk of severe or end-stage kidney disease was 10.32% for those who achieved the target serum urate level and 12.73% for those who did not. Compared with those not achieving the target level, the adjusted 5-year risk difference and HR of severe or end-stage kidney disease for patients achieving the target serum urate level was -2.41% (95% CI, -4.61% to -0.21%) and 0.89 (95% CI, 0.80 to 0.98), respectively.Conclusions and relevanceThe findings of this cohort study indicate that in patients with gout and CKD stage 3, lowering serum urate level to less than 6 mg/dL vs 6 mg/dL or greater using ULT was not associated with an increased risk of severe or end-stage kidney disease. These findings support optimizing ULT to achieve target serum urate levels when treating patients with gout and impaired kidney function.

Gouty arthritis (GA) is an inflammatory disease caused by monosodium urate (MSU) crystals deposited in the joint tissues causing severe pain. The disease can recur frequently and tends to form tophus in the joints. Current therapeutic drugs for the acute phase of GA have many side effects and limitations, are unable to prevent recurrent GA attacks and tophus formation, and overall efficacy is unsatisfactory. Therefore, we need to advance research on the microscopic mechanism of GA and seek safer and more effective drugs through relevant targets to block the GA disease process. Current research shows that the pathogenesis of GA is closely related to NLRP3 inflammation, oxidative stress, MAPK, NET, autophagy, and Ferroptosis. However, after synthesizing and sorting out the above mechanisms, it is found that the presence of ROS is throughout almost the entire spectrum of micro-mechanisms of the gout disease process, which combines multiple immune responses to form a large network diagram of complex and tight connections involved in the GA disease process. Current studies have shown that inflammation, oxidative stress, cell necrosis, and pathological signs of GA in GA joint tissues can be effectively suppressed by modulating ROS network-related targets. In this article, on the one hand, we investigated the generative mechanism of ROS network generation and its association with GA. On the other hand, we explored the potential of related targets for the treatment of gout and the prevention of tophus formation, which can provide effective reference ideas for the development of highly effective drugs for the treatment of GA.

IntroductionGut microbiota modulation has recently been identified as a prospective avenue for the exploration of novel therapeutic strategies for the management of gout. Nevertheless, the application of a single specific strain or bacterial metabolite for gout intervention has rarely been explored and the underlying regulatory mechanism remains elusive.ObjectivesTo ascertain the potential role and the molecular mechanism of Clostridium butyricum and butyrate in the management of gouty arthritis.MethodsA Uox-KO mouse model of gouty arthritis was developed and the composition of the gut microbiota was analyzed. C. butyricum and butyrate were supplemented to assess functional recovery and intestinal homeostasis. NanoString analysis identified miRNA variations. GC/MS measured butyric acid levels and qPCR detected the abundance of butyrate-producing enzymes and bacteria. Flow cytometry analyzed macrophage polarization and ELISA measured pro-inflammatory cytokine production. Agomir and antagomir were transfected and dual-luciferase reporter assay was adapted for validation of miRNA target binding. siRNA and rescue experiments were performed to validate the role of SOCS7 in macrophage polarization. In addition, a cohort of patients with gouty arthritis were assembled for the purpose of validating the molecular mechanism.ResultsThe results of our study demonstrated that a reduction of butyrate levels, resulting from a deficiency of butyrate-producing bacteria, leads to aberrant miR-146a expression. This, in turn, induces an imbalance in macrophage polarization and the onset of gouty arthritis. The administration of C. butyricum and butyrate demonstrated considerable anti-inflammatory efficacy by restoring intestinal homeostasis, modulating miR-146a expression, and skewing macrophage polarization. The SOCS7/JAK2-STAT3 signaling pathway was identified as a pivotal mediator in the skewing of macrophage polarization induced by miR-146a.ConclusionOur findings enrich the understanding of the regulatory mechanisms underlying macrophage polarization in gouty arthritis and highlight the potential applications of probiotics and their metabolites in clinical gout treatment.