Incidence Of Gout Research Articles

Increased risk of incident gout in young men with metabolic syndrome: A nationwide population-based cohort study of 3.5 million men.

To date, few studies have focused on risk factors for gout in young people, and large-scale studies on the relationship between metabolic syndrome (MetS) and gout are lacking. We aimed to investigate the association between gout and MetS in a large nationwide population-based cohort of young men who participated in national health examination. Cohort included men aged 20-39 years who participated in a health check-up in 2009-2012. A total of 3,569,104 subjects was included in the study, excluding those who had a previous diagnosis of gout or had renal impairment. The outcome was the occurrence of gout, which was defined using the diagnosis code of gout in the claims database. Cox proportional hazard model was used to evaluate the association between MetS and incident gout. Mean follow-up duration was 7.35 ± 1.24 years and the incidence rate of gout was 3.36 per 1,000 person-years. The risk of gout in subjects with MetS was 2.4-fold higher than subjects without MetS. Among the components of MetS, hypertriglyceridemia and abdominal obesity showed the greatest association with gout. As the number of MetS components increased, the risk of gout increased. The association between gout and MetS was more pronounced in relatively young subjects and in low- or normal-weight subjects. Metabolic syndrome is an important risk factor for the gout in young men. In particular, the association between MetS and gout was greater in young and non-obese men. Management of MetS in young men will be important for future gout prevention.

Treat-to-target urate-lowering therapy and hospitalizations for gout: results from a nationwide cohort study in England.

To investigate associations between treat-to-target urate-lowering therapy (ULT) and hospitalizations for gout. Using linked Clinical Practice Research Datalink and NHS Digital Hospital Episode Statistics data, we described the incidence and timing of hospitalizations for flares in people with index gout diagnoses in England from 2004-2020. Using Cox proportional hazards and propensity models, we investigated associations between ULT initiation, serum urate target attainment, colchicine prophylaxis, and the risk of hospitalizations for gout. Of 292 270 people with incident gout, 7719 (2.64%) had one or more hospitalizations for gout, with an incidence rate of 4.64 hospitalizations per 1000 person-years (95% CI 4.54, 4.73). There was an associated increased risk of hospitalizations within the first 6 months after ULT initiation, when compared with people who did not initiate ULT [adjusted Hazard Ratio (aHR) 4.54; 95% CI 3.70, 5.58; P < 0.001]. Hospitalizations did not differ significantly between people prescribed vs not prescribed colchicine prophylaxis in fully adjusted models. From 12 months after initiation, ULT associated with a reduced risk of hospitalizations (aHR 0.77; 95% CI 0.71, 0.83; P < 0.001). In ULT initiators, attainment of a serum urate <360 micromol/l within 12 months of initiation associated with a reduced risk of hospitalizations (aHR 0.57; 95% CI 0.49, 0.67; P < 0.001) when compared with people initiating ULT but not attaining this target. ULT associates with an increased risk of hospitalizations within the first 6 months of initiation but reduces hospitalizations in the long term, particularly when serum urate targets are achieved.

The burden of gout in acne keloidalis nuchae-Insights from a population-based study.

The risk of gout amid patients with acne keloidalis nuchae (AKN) has not been investigated in the past. To assess the risk of developing gout among patients with AKN relative to control subjects. A population-based retrospective study followed patients with AKN (n=2677) and age-, sex-, and ethnicity-matched control subjects (n=13 190). The incidence of new-onset gout was compared between the two groups. Hazard ratio (HR) for the risk of gout was obtained using a multivariate Cox regression model. The incidence rate of gout was 1.12 (95% CI, 0.68-1.76) and 0.48 (95% CI, 0.34-0.66) per 1000 person-years among patients with AKN and controls, respectively. The crude risk of developing gout was significantly higher in patients with AKN (HR, 2.27; 95% CI, 1.26-4.10; p=0.007). After controlling for age, sex, and ethnicity, AKN emerged as an independent risk factor of gout (adjusted HR, 2.34; 95% CI, 1.29-4.22; p=0.005). When adjusting for other confounders such as body mass index, diabetes mellitus, hypertension, and dyslipidemia, the risk of gout in AKN fell out of significance (adjusted HR, 1.39; 95% CI, 0.73-2.65; p=0.311), CONCLUSION: Patients with AKN experience an increased risk of gout. The risk is not independent and is mainly mediated through the metabolic comorbidities typifying AKN. We recommend screening for gout in patients with suggestive complaints.

Gout in Dalarna, Sweden – a population-based study of gout occurrence and compliance to treatment guidelines

Objective This study aimed to describe the incidence and prevalence of gout, describe the use of allopurinol among prevalent gout cases, and determine persistence with allopurinol and degree of compliance with treat-to-target recommendations before and after the publication of Swedish national guidelines in 2016. Method Prospectively registered data on gout diagnoses and allopurinol prescriptions were used to calculate incidence and prevalence, and the proportion of prevalent patients on allopurinol. Gout patients starting allopurinol during 2013–2015 versus 2016–2018 were compared regarding persistence and compliance with treat-to-target principles. Results The incidence of gout was 221–247 per 100 000 person-years during 2014–2019, prevalence in 2018 was 2.45%. Among prevalent cases, the proportion on allopurinol ranged from 21% to 25%. Allopurinol persistence was better for individuals starting therapy during 2016–2018 compared with 2013–2015 (45% vs 39%, p = 0.031), as were several outcomes related to treat-to-target principles, e.g. measuring baseline serum urate (SU) (84% vs 77%, p < 0.001), follow-up SU (50% vs 36%, p < 0.001), and the proportion of patients reaching an SU level < 360 µmol/L (45% vs 30%, p < 0.001). Conclusion Incidence and prevalence were slightly higher than in previous Swedish reports. Allopurinol use among prevalent gout patients did not increase during 2014–2019. Only a minor improvement in persistence was seen, and a moderate increase in compliance with guidelines, suggesting a need for improved management and extended patient involvement to increase and optimize the use of urate lowering therapy.

Recovery of patients with gout

Introduction. The incidence and prevalence of gout have increased worldwide in recent decades. Scientists at the Rochester Epidemiology Project (MN, USA) have seen a two-fold increase in the incidence of primary gout (patients without diuretic exposure) over a 20-year period, which ended in 1996. The increase of incidence may be related due to the difficulty and often unsatisfactory treatment options. The aim of the study was to systematize the recommendations on dietary treatment, and medication for patients with gout. Materials and methods. An analytical, qualitative, and secondary study was performed in the form of a synthesis article. 115 sources were identified and analyzed; from this list, 44 sources were selected according to the impact score during the publication period and according to the level of recommendations. Results. 44 articles were included. Most studies were small, retrospective analyses performed in single centers, with concerns for bias. Eleven studies (including five randomized controlled trials) reported improved patient outcomes following pharmacological interventions with known efficacy in gout, including allopurinol, prednisolone, NSAIDs and anakinra. Eight studies reported improved outcomes associated with non-pharmacological interventions: inpatient rheumatology consultation and a hospital gout management protocol. No studies to date have prospectively evaluated strategies designed to prevent re-admissions of patients hospitalized for gout flares. Conclusions. Urate crystals is completely soluble when we can lower the serum level of uric acid to normal values, but this often requires long-term treatment. The early onset of rehabilitation of affected joints helps to reduce the articular inflammatory process, the pain syndrome and it delays the progression of the underlying pathology while improving the quality of life in patients with gout. Further research is needed to enable healthcare providers to individualize and optimize gout treatment strategies, ensuring that patients with gout receive effective, safe, and high-quality care.

Associations of habitual glucosamine supplementation with incident gout: a large population based cohort study

ObjectivesThe association between habitual glucosamine use and incident gout has not been examined in previous studies. We aimed to evaluate the association of habitual use of glucosamine with the risk of gout in general population.MethodsA total of 436,594 participants (55.4% female) without prior gout at baseline who completed a questionnaire on supplementation use, which included glucosamine, in the UK Biobank were enrolled. Incident gout was recorded from self-report, death register, primary care, and hospital admission data.ResultsAt baseline, 53,433 (22.1%) females and 30,685 (15.8%) males reported habitual glucosamine use. During a median follow-up period of 12.1 years, 1718 (0.7%) females and 5685 (2.9%) males developed gout. After multivariable adjustment for major risk factors, glucosamine use was associated with a significantly lower risk of incident gout in females (hazard ratio [HR], 0.81, 95% confidence interval [CI], 0.71–0.92), but not in males (HR, 1.05, 95% CI, 0.97–1.13), compared with non-use (P-interaction < 0.001). Among females, the inverse association between glucosamine use and gout was stronger in participants with diuretics use (HR, 0.64, 95% CI, 0.50–0.81) than those without diuretics use (HR, 0.89, 95% CI, 0.77–1.03) (P-interaction = 0.015). Moreover, gout genetic risk scores did not significantly modify the association between glucosamine use and the risk of incident gout in males (P-interaction = 0.548) or females (P-interaction = 0.183).ConclusionsHabitual glucosamine use to relieve osteoarthritis pain was related to lower risk of gout in females, but not in males.

Sodium-glucose cotransporter-2 inhibitors and the risk of gout in patients with type 2 diabetes mellitus: A propensity-score-matched, new-user design study with an active comparator using the IQVIA Medical Research Data UK database.

To conduct a pharmacoepidemiological study to explore the association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and gout in patients with type 2 diabetes mellitus (T2DM). A retrospective open cohort study using the IQVIA Medical Research Data UK database was performed between November 1, 2012 and December 31, 2018, estimating the risk of gout in patients with T2DM who were new users of SGLT2 inhibitors, compared to propensity-score-matched new users of dipeptidyl peptidase-4 (DPP-4) inhibitors. A total of 85 incident cases of gout were recorded over 30 389 person-years of observation in 13 617 new users of SGLT2 inhibitors and 29 426 new users of DPP-4 inhibitors. Crude incidence rates (IRs) per 1000 person-years were 2.90 and 2.47 for new users of SGLT2 inhibitors and DPP-4 inhibitors, respectively. The unadjusted hazard ratio (HR) was 1.18 (95% confidence interval [CI] 0.76-1.83). The adjusted HR was 1.20 (95% CI 0.77-1.86). In the at-treatment analysis, crude IRs per 1000 person-years were found to be 2.68 and 2.53 for SGLT2 inhibitor and DPP-4 inhibitor users, respectively. In the adjusted model, the adjusted HR was 1.3 (95% CI 0.90-2.29). Sensitivity analyses did not change the findings. In this nationwide study, no difference in the incidence of gout was documented in patients treated with SGLT2 inhibitors compared to DPP-4 inhibitor users. This neutral finding remained consistent in sensitivity analyses.

Computed tomography and magnetic resonance imaging findings in gouty arthritis involving large joints of the upper extremities

BackgroundWe aimed to analyze the computed tomography (CT) and magnetic resonance imaging (MRI) findings of gouty arthritis primarily involving the large joints of the upper limbs, signal or density characteristics of the tophi, growth patterns, involvement of the adjacent joints, and differentiation from other lesions occurring in this area and to discuss the causes of misdiagnosis.MethodsCT and MRI data were collected from 14 patients with gouty arthritis, primarily involving the shoulder and elbow joints, and their imaging features were analyzed.ResultsAll the patiens were ranged from 28-85 years old, and the tophi deposition can be observed on either CT or MRI.The tophi deposition apperas as slightly higher density nodules or masses on CT images,or nodules or masses on MRI with isosignal/hypointensity on T1WI and hyperintensity on T2WI. Five patients showed narrowing of the affected joint space, four had different degrees of bone erosion under the articular surface, eight developed joint effusion, and all showed surrounding soft tissue swelling. The tophi grew around the joint, with anterolateral and posterolateral tophi predominantly in the shoulder joint and dorsal tophi predominantly in the elbow joint on the MRI, with compression and edema of the surrounding soft tissues.ConclusionsGouty arthritis occurs in the large joints of the upper limbs and is characterized by fluid accumulation in the joint capsule and the formation of tophi. These tophi are usually large, with subcutaneous bone resorption and erosion, with or without cartilage destruction. However, extensive edema appeared in the soft tissue around the tophi, but the edema only produced pressure without any obvious signs of soft tissue infiltration, which may be distinguished from the joint tumor. In addition, the gout incidence rate is increased in young patients. Therefore, when the patient has a large joint mass, it is important to confirm whether there is a history of gout.

The effects of aerobic exercise on body composition in overweight and obese patients with gout: a randomized, open-labeled, controlled trial

BackgroundOverweight and obesity are typical risk factors for the increased prevalence and incidence of gout. The existing guidelines unequivocally indicated that exercise is highly advantageous for patients with gout. Nevertheless, there is still a lack of specific guidance and clinical evidence. The effects of exercise on improving gout, and the optimal frequency, timing, and types of exercise have not been fully clarified. The present trial aims to determine the effects of a specific aerobic exercise program on body composition in overweight and obese patients with gout.MethodsIn this randomized, open-labeled, controlled trial, a total of 60 overweight and obese patients with gout [body mass index (BMI) ≥ 24 kg/m2; age,18–55 years old] are equally randomized (1:1) into two groups (n = 30): moderate-intensity aerobic exercise group (MIAEG), heart rate reserve (HRR) = [(HRmax-HRrest) × 60% intensity] + HRrest, and control group (CG). The moderate-intensity aerobic exercise training program will be conducted for 30–40 min/session and 3 days/week for 12 weeks. Participants in the CG will be asked to avoid making changes in their exercise habits. There will be no limitation in the type of exercise. The primary outcome is the number of patients whose body fat is reduced after 12 weeks. The secondary outcomes include the changes in BMI, waist-to-hip ratio (WHR), insulin resistance index (IRI), serum uric acid (sUA), serum creatinine (SCr), estimated glomerular filtration rate (eGFR), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hepatic steatosis, and adverse effects after 12 weeks. One-way analysis of variance (ANOVA) will be used to compare the mean values of normally distributed variables between MIAEG and GC.DiscussionThe effect and optimal frequency of exercise for improving the status of overweight and obese patients with gout have not yet been determined. We design a 12-week randomized controlled trial and evaluate the effects of individualized aerobic exercise program on patients with gout. The results may assist such patients with a personalized scientific exercise program based on the disease status and motor abilities, so that patients are prone to exercise under the condition of low risk and achieve the greatest benefits.Trial registrationChiCTR2200062153. Registered on July 25, 2022, with ChiCTR. http://www.chictr.org.cn/

Comparative efficacy and safety of uricosuric agents in the treatment of gout or hyperuricemia: a systematic review and network meta-analysis.

The current world witnesses a greatly increased prevalence and incidence of hyperuricemia and gout with unfortunately the comparative efficacy and safety of present available uricosuric agents remaining uncertain. We herein aimed to investigate the most appropriate uricosuric agent for gout or hyperuricemia patients. PubMed, Embase, Cochrane Library databases, and ClinicalTrials.gov from inception to 2 July 2022 were searched to retrieve eligible studies assessing efficacy and safety of uricosuric drugs in hyperuricemia or gout patients. Network meta-analysis was carried out using the Stata 16.0 software. Twelve randomized controlled trials comprising 1851 patients were eventually included. Network meta-analysis showed that dotinurad 4mg once daily, verinurad, dotinurad 2mg once daily, dotinurad 1mg once daily, and benzbromarone were the top 5 effective treatments to achieve target serum uric acid. Furthermore, dotinurad 4mg once daily was more effective at achieving urate-lowering targets (RR of dotinurad 4mg once daily vs. probenecid: 1.68, 95% CI [1.13; 2.50]) and safer (RR of probenecid vs. dotinurad 4mg once daily: 1.77, 95% CI [0.69; 4.56]) than probenecid. This network meta-analysis demonstrated an important absolute benefit of dotinurad 4mg once daily to achieve target serum uric acid and low risk of adverse events for drug treatment of gout or hyperuricemia patients. Additionally, verinurad might be used as an alternative uricosuric therapeutic option to dotinurad. These findings provided further comprehensive insight into the treatment value of current uricosuric agents for gout or hyperuricemia. Key Points 1. This is the first systematic review and network meta-analysis examining the efficacy and safety of currently available uricosuric agents in gout or hyperuricemia patients. 2. Recommended doses of dotinurad 4mg once daily used for the treatment of gout or hyperuricemia patients can significantly decrease serum uric acid levels. 3. The present findings will provide further comprehensive insight into the treatment value of certain uricosuric agents for gout or hyperuricemia.

Risk of a major adverse cardiovascular event (MACE) following first-ever hospitalisation for acute gout: a Western Australian population-level linked data study.

ObjectivesCardiovascular disease is the largest contributor of increased mortality in patients with gout. Acute inflammation as seen with gout attacks may have a mechanistic role in developing Major Adverse Cardiovascular Events (MACE). We examined the temporal relationship between admission to hospital with acute gout and MACE. ApproachLinked inpatient and mortality data from the Western Australian Rheumatic Disease Epidemiology Registry were used. We identified patients with an incident acute gout (index) hospitalisation and admission or death records due to MACE (composite of acute coronary syndrome, stroke, heart failure, cardiovascular death). The risk of MACE during the index post-discharge period (1-30 days after index admission) and control period (365 days prior to index admission and 365 days post-discharge) was determined using a self-controlled case-series (SCCS) design. Conditional fixed-effects Poisson regression was used to obtain incidence rate ratios (IRR). Sensitivity analyses were performed excluding deaths and 180-day events. ResultsWe identified 962 patients (mean age=76.2 years [SD=12.2]; 66.8% male) with incident acute gout admission and documented MACE during the control and/or index post-discharge periods. 917 (95.3%) patients experienced MACE during the control period and 114 (11.9%) during the index post-discharge period. The rate of MACE during the control and post-discharge periods were 0.84 and 1.44 events per person-year, respectively, with an IRR=1.67 (95% CI: 1.38-2.02) for the post-discharge period compared with the control period from regression analysis. Sensitivity analyses excluding deaths and 180-day events were IRR=1.68 (95% CI=1.29-2.20) and IRR=1.66 (95% CI=1.34-2.07) respectively. ConclusionOur self-controlled case-series study using linked administrative data found an increased risk of MACE during the 30 days after discharge for index gout hospitalisation. This suggests a temporal association between acute inflammation and MACE.

Gut microbiota remodeling: A promising therapeutic strategy to confront hyperuricemia and gout.

The incidence of hyperuricemia (HUA) and gout continuously increases and has become a major public health problem. The gut microbiota, which colonizes the human intestine, has a mutually beneficial and symbiotic relationship with the host and plays a vital role in the host’s metabolism and immune regulation. Structural changes or imbalance in the gut microbiota could cause metabolic disorders and participate in the synthesis of purine-metabolizing enzymes and the release of inflammatory cytokines, which is closely related to the occurrence and development of the metabolic immune disease HUA and gout. The gut microbiota as an entry point to explore the pathogenesis of HUA and gout has become a new research hotspot. This review summarizes the characteristics of the gut microbiota in patients with HUA and gout. Meanwhile, the influence of different dietary structures on the gut microbiota, the effect of the gut microbiota on purine and uric acid metabolism, and the internal relationship between the gut microbiota and metabolic endotoxemia/inflammatory factors are explored. Moreover, the intervention effects of probiotics, prebiotics, and fecal microbial transplantation on HUA and gout are also systematically reviewed to provide a gut flora solution for the prevention and treatment of related diseases.

The Benefits of Acupuncture Combined with a Low Purine Diet to Improve Uric Acid and Total Cholesterol in Diabetes Mellitus Patients with Hyperuricemia

Background: Diabetes mellitus with hyperuricemia causes the accumulation of monosodium urate crystals in the synovial joint tissue. The incidence of gout in Indonesia according to the Indonesian Rheumatology Association, namely: gout 1-2 percent of adults, is the most cases of arthritis in men and is estimated to be between 13.6 per 1,000 men and 6.4 per 1,000 women. The prevalence of gout increased with age, an average of 7 percent of men &gt;75 years and 3 percent of women &gt;85 years.Subjects dan Method: Quasi-Experimental with pre and post-test designs. The research time is between March to September 2021 at the Posyandu for the elderly in Surakarta City. The population of this study were all objects with fasting blood sugar levels between 100 mg/dl - 125 mg/dl and above 126 mg/dl, female blood uric acid levels exceeding 5.6 mg/dl in men and exceeding 6.5 in the city. Surakarta, sample selection using purposive sampling, sample size 40 subjects. The dependent variable is uric acid, cholesterol and total blood levels, the independent variable is combination acupuncture therapy with a low purine diet. The research instrument used a checklist for blood analysis and physical examination. Data analysis using t-test.Results: Uric acid levels after acupuncture therapy in the intervention group were lower (Mean= 3.31; SD= 0.61) than the control group (Mean= 5.83; SD= 1.29), and not statistically significant (p= 0.935). Total cholesterol level after acupuncture therapy in the intervention group was lower (Mean= 166.00; SD= 34.20) than the control group (Mean= 222.30; SD= 55.43), but it was statistically non-significant (p= 0.676).Conclusion: Acupuncture therapy can reduce uric acid levels and total cholesterol levels. Keywords: Acupuncture, low purine diet, uric acid level, cholesterol level Correspondence:Sumanto. College Leading Basic Research, Acupuncture Course, Health Polyetchnics, Ministry of Health Surakarta. Jl. Letjend Sutoyo Mojosongo, Surakarta, Central Java. Email: sumantoiman@gmail.com. Mobile phone: 08121608067.

2022 update of the Austrian Society of Rheumatology and Rehabilitation nutrition and lifestyle recommendations for patients with gout and hyperuricemia

BackgroundGout is the most frequent inflammatory joint disease in the western world and has a proven genetic background. Additionally, lifestyle factors like increasing life span and wealth, sufficient to excess nutritional status and a growing prevalence of obesity in the population, as well as e.g. alcohol consumption contribute to the rising incidence of hyperuricemia and gout. Apart from an adequate medication, medical advice on nutrition and lifestyle is an essential part of the management of gout patients, being at high risk of internal comorbidities.ObjectiveIn 2015, the ÖGR (Österreichische Gesellschaft für Rheumatologie und Rehabilitation) working group for osteoarthritis and crystal arthropathies already published nutrition and lifestyle recommendations for patients with gout and hyperuricemia. Since then, a multitude of literature has been published addressing this topic, what required an update.MethodsFirst, the authors performed a hierarchical literature search to screen the meanwhile published literature. Also considering references of the first publication, the relevant literature was selected, and the 2015 recommendations were either kept as published, reformulated or newly produced. Finally, the evidence level and the level of agreement with each recommendation were added.ResultsFollowing this process, ten recommendations were generated instead of the initial nine. Like in the original publication, a colored icon presentation was provided to complement the written text.ConclusionThe Austrian nutrition and lifestyle recommendations for patients with gout and hyperuricemia were updated incorporating the most recent relevant literature, serving as education material for patients and updated information for physicians.

Mapping Knowledge Structure and Global Research Trends in Gout: A Bibliometric Analysis From 2001 to 2021.

BackgroundThe incidence and prevalence of gout have been steadily increasing globally, which has resulted in gout research attracting consistently increased attention. This study aimed to visualize the knowledge structure and research trends in gout research through bibliometrics to help understand the future development of basic and clinical research.MethodsArticles and reviews on gout from 2001 to 2021 were extracted from the Web of Science Core Collection database. CiteSpace and VOSviewer software were used to visualize the knowledge network of countries, institutions, authors, references, and keywords in this field. SPSS and Microsoft Excel software were used for curve fitting and correlation analysis.ResultsA total of 3,259 articles and reviews were included. The number of publications about gout significantly increased yearly. Publications were mainly concentrated in North America, Europe, Oceania, and East Asia. The USA contributed most with 1,025 publications, followed by China and New Zealand. After adjusting for publications by population size and Gross Domestic Product (GDP), New Zealand ranked in the first place. GDP and international collaboration were significantly correlated with scientific productivity for gout research. University of Auckland and Professor Dalbeth Nicola were the most prolific institutions and influential authors, respectively. Rheumatology was the most productive journal for gout research. Gout research hotspots have shifted over time in the following order: clinical features, pathological mechanisms, complications, gouty arthritis, epidemiology, and dual-energy computed tomography to drug clinical trials, which can be observed from the keyword analysis and co-cited reference cluster analysis.ConclusionsThis study found that research on gout is flourishing. The development and experimentation of drugs for the prevention and treatment of gouty arthritis would be the focus of current research and developmental trends in future research.

Trends in the Contribution of Genetic Susceptibility Loci to Hyperuricemia and Gout and Associated Novel Mechanisms.

Hyperuricemia and gout are complex diseases mediated by genetic, epigenetic, and environmental exposure interactions. The incidence and medical burden of gout, an inflammatory arthritis caused by hyperuricemia, increase every year, significantly increasing the disease burden. Genetic factors play an essential role in the development of hyperuricemia and gout. Currently, the search on disease-associated genetic variants through large-scale genome-wide scans has primarily improved our understanding of this disease. However, most genome-wide association studies (GWASs) still focus on the basic level, whereas the biological mechanisms underlying the association between genetic variants and the disease are still far from well understood. Therefore, we summarized the latest hyperuricemia- and gout-associated genetic loci identified in the Global Biobank Meta-analysis Initiative (GBMI) and elucidated the comprehensive potential molecular mechanisms underlying the effects of these gene variants in hyperuricemia and gout based on genetic perspectives, in terms of mechanisms affecting uric acid excretion and reabsorption, lipid metabolism, glucose metabolism, and nod-like receptor pyrin domain 3 (NLRP3) inflammasome and inflammatory pathways. Finally, we summarized the potential effect of genetic variants on disease prognosis and drug efficacy. In conclusion, we expect that this summary will increase our understanding of the pathogenesis of hyperuricemia and gout, provide a theoretical basis for the innovative development of new clinical treatment options, and enhance the capabilities of precision medicine for hyperuricemia and gout treatment.

Evaluation of the safety and efficacy of a Fuling-Zexie decoction for people with asymptomatic hyperuricemia: protocol for a prospective, double-blinded, randomized, placebo-controlled clinical trial

BackgroundHyperuricemia increases the risk of gout and cardiovascular complications, and how to manage asymptomatic hyperuricemia is controversial. Randomized controlled trials and comparative studies are needed to guide management and treatment. Studies show that Chinese medicine can decrease uric acid through multiple targets, but many of these studies have been conducted in animals because of the lack of a consistent prescription and mechanism. Therefore, we designed this research to study whether Chinese medicine is truly effective and which target is essential by using an approved prescription of a Fuling-Zexie decoction to further guide large sample experiments to determine whether Chinese medicine can reduce the long-term incidence of gout and cardiovascular events.MethodsThis pilot study is a prospective, double-blinded, randomized, placebo-controlled clinical trial developed from March 2020 to December 2021. Thirty people with asymptomatic hyperuricemia will be recruited and assigned to either the Chinese medicine group or placebo group, and each group will have 15 subjects. During the 12-week observation period, there will be 4 visits. The decline in uric acid is the main outcome measure, and urinary uric acid, inflammatory biomarkers, and other indices that may be involved in lowering uric acid are the secondary outcome measures.DiscussionThis study will probe the effect of Chinese medicine treatment on hyperuricemia and explore possible therapeutic mechanisms. By performing this trial, we hope to provide evidence and data to support further large clinical studies.Trial registrationChiCTR2000038575. Registered on September 24, 2020.

TET2-mutant clonal hematopoiesis and risk of gout

AbstractGout is a common inflammatory arthritis caused by precipitation of monosodium urate (MSU) crystals in individuals with hyperuricemia. Acute flares are accompanied by secretion of proinflammatory cytokines, including interleukin-1β (IL-1β). Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition predisposing to hematologic cancers and cardiovascular disease. CHIP is associated with elevated IL-1β, thus we investigated CHIP as a risk factor for gout. To test the clinical association between CHIP and gout, we analyzed whole exome sequencing data from 177 824 individuals in the MGB Biobank (MGBB) and UK Biobank (UKB). In both cohorts, the frequency of gout was higher among individuals with CHIP than without CHIP (MGBB, CHIP with variant allele fraction [VAF] ≥2%: odds ratio [OR], 1.69; 95% CI, 1.09-2.61; P = .0189; UKB, CHIP with VAF ≥10%: OR, 1.25; 95% CI, 1.05-1.50; P = .0133). Moreover, individuals with CHIP and a VAF ≥10% had an increased risk of incident gout (UKB: hazard ratio [HR], 1.28; 95% CI, 1.06-1.55; P = .0107). In murine models of gout pathogenesis, animals with Tet2 knockout hematopoietic cells had exaggerated IL-1β secretion and paw edema upon administration of MSU crystals. Tet2 knockout macrophages elaborated higher levels of IL-1β in response to MSU crystals in vitro, which was ameliorated through genetic and pharmacologic Nlrp3 inflammasome inhibition. These studies show that TET2-mutant CHIP is associated with an increased risk of gout in humans and that MSU crystals lead to elevated IL-1β levels in Tet2 knockout murine models. We identify CHIP as an amplifier of NLRP3-dependent inflammatory responses to MSU crystals in patients with gout.

Biochemical aspects of gout pharmacotherapy with colchicine and allopurinol

Gout is translated from Greek as “like a foot-trap”, and this disease is also known as the “disease of the aristocrats”. Gout has been known to mankind since ancient times; the first written mention of gout was found in ancient Egypt, then this topic was raised more than once in the works of such pillars of medicine as Hippocrates, Celsus, and Galen. This problem remains relevant in the modern world as well. Most often, men over 40 years of age suffer from this disease, but there is currently an increase in the incidence of gout, including in women and young people. So, what is gout? Gout is a chronic polyetiological disease associated with a purine metabolism disorder, characterize by an increase in the level of uric acid in the blood (hyperuricemia) and the deposition of the sodium salt of uric acid (urate) in the joints, periarticular tissues and internal organs with the development of recurrent arthritis and the formation of gouty nodules (tophi). The aim of our research was to study the features of gout pharmacotherapy. To achieve it, the following tasks were set and fulfilled: the mechanism of development of gout as a hereditary polyetiological disease was considered, and the biochemical aspects of the formation and course of the disease were highlighted. Treatment is prescribed depending on the period of the disease, including drugs for stopping an attack (NSAIDs, colchicine, corticosteroids and monoclonal antibodies) and maintenance therapy in the interictal period (allopurinol and uricosuric drugs). In the course of the work, we were interested in the mechanisms of action of drugs such as allopurinol and colchicine, therefore, these were given special attention.

Novel lactic acid bacteria with anti-hyperuricemia ability: Screening and in vitro probiotic characteristics

Hyperuricemia has been identified as the second most common metabolic disease, increasing the incidence of gout, hypertension, kidney disease, and cardiovascular disease. Lactic acid bacteria have been attracting considerable interest in anti-hyperuricemia given various probiotic functions. In this study, sixteen lactic acid bacteria were selected from one hundred ninety-two isolates through whole-cell catalysis, affording β-D-glucosidase activity of 0.1652–0.3346 U/mg wet cells, degradation rate of inosine-transformed rate of 1.2125–4.6555 mM/h and guanosine-transformed rate of 0.2904–1.8303 mM/h. The sixteen candidates’ acid tolerance, bile resistance, hydrophobicity, and auto-aggregation were further evaluated. According to the results of the seven indexes, the five top-scored strains were viewed as the potentially functional probiotics for anti-hyperuricemia via the comprehensive evaluation of principal component analysis. Cell assay showed that the adhesion of the five strains to Caco-2 cells ranged from 2.67% to 8.67%. Moreover, the five strains can decrease the adhesion of E. coli to Caco-2 cells by 36.67–98.73% through competition inhibition, exclusion inhibition, and replacement inhibition. Finally, the five probiotics were sensitive to some of the antibiotics examined and were innocuous with nonhemolytic activity. The preliminary works indicate that the five candidates could show a good potential application against hyperuricemia.