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    The impact of gout guidelines. Wise Eric,Khanna Puja P Current opinion in rheumatology PURPOSE OF REVIEW:This review discusses the impact of recent treatment guidelines for the management of gout and the barriers to treating gout patients. RECENT FINDINGS:Multiple guidelines for both the treatment and prevention of gout have been put forth in the last decade including those from the British Rheumatism Society; the European League Against Rheumatism; the Multinational Evidence, Expertise, Exchange Initiative; the Japanese Society of Gout and Nucleic Acid Metabolism; the American College of Rheumatology. These guidelines are designed to facilitate the management of gout by providers with key recommendations for the management of hyperuricemia, which is the greatest risk factor for developing gout. However, despite the extant guidelines, overall adherence to recommendations and uptake have been slow and initiation of urate-lowering therapy, titration of dosing, and monitoring of serum urate is infrequent. Greater education in proper management as well as increased awareness of new treatment strategies appear to be the primary reasons for this gap and offer avenues for improvement in management as well as areas for further research. SUMMARY:Gout remains a treatment challenge for both acute and chronic disease. Despite the availability of management guidelines, primary care providers are struggling with appropriate management of the disease. More research tools and strategies are needed to improve overall outcomes and quality of care. 10.1097/BOR.0000000000000168
    Japanese guideline for the management of hyperuricemia and gout: second edition. Yamanaka Hisashi, Nucleosides, nucleotides & nucleic acids Gout is a urate deposition disease caused by persistent hyperuricemia. Because gout patients present with a variety of clinical symptoms, it is necessary to have a guideline for the standard management and care of gout and hyperuricemia. The Japanese Society of Gout and Nucleic Acid Metabolism, a scientific society committed to study nucleic acid metabolism and related diseases, established the first edition of the "Guideline for the Management of Hyperuricemia and Gout" in 2002, and published the revised version in January 2010. This second edition is not only evidence based on a search of systemic literature, but also includes consensus levels by a Delphi exercise to determine the strength of the recommendations. A draft version of this guideline was reviewed by internal and external reviewers as well as a patient. In this guideline, key messages from each chapter are listed as statements together with the evidence level, consensus level, and strength of the recommendation. In this proceeding, several selected chapters on the clinical management of gout and hyperuricemia are described. We hope this guideline is appropriately used for the standard management and care of patients with hyperuricemia and gout in daily practice. 10.1080/15257770.2011.596496
    Management of gout and hyperuricemia: Multidisciplinary consensus in Taiwan. Yu Kuang-Hui,Chen Der-Yuan,Chen Jiunn-Horng,Chen Shih-Yang,Chen Shyh-Ming,Cheng Tien-Tsai,Hsieh Song-Chou,Hsieh Tsu-Yi,Hsu Pai-Feng,Kuo Chang-Fu,Kuo Mei-Chuan,Lam Hing-Chung,Lee I-Te,Liang Toong-Hua,Lin Hsiao-Yi,Lin Shih-Chang,Tsai Wen-Pin,Tsay Gregory J,Wei James Cheng-Chung,Yang Chung-Han,Tsai Wen-Chan International journal of rheumatic diseases Gout is an inflammatory disease manifested by the deposition of monosodium urate (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues. Gout is not a new disease, which was first documented nearly 5,000 years ago. The prevalence of gout has increased globally in recent years, imposing great disease burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a variety of comorbidities, including cardiovascular diseases, chronic kidney disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid dysfunction, and psoriasis. To prevent acute arthritis attacks and complications, earlier use of pharmacotherapeutic treatment should be considered, and patients with hyperuricemia and previous episodes of acute gouty arthritis should receive long-term urate-lowering treatment. Urate-lowering drugs should be used during the inter-critical and chronic stages to prevent recurrent gout attacks, which may elicit gradual resolution of tophi. The goal of urate-lowering therapy should aim to maintain serum uric acid (sUA) level <6.0 mg/dL. For patients with tophi, the initial goal can be set at lowering sUA to <5.0 mg/dL to promote tophi dissolution. The goal of this consensus paper was to improve gout and hyperuricemia management at a more comprehensive level. The content of this consensus paper was developed based on local epidemiology and current clinical practice, as well as consensuses from two multidisciplinary meetings and recommendations from Taiwan Guideline for the Management of Gout and Hyperuricemia. 10.1111/1756-185X.13266
    Suboptimal physician adherence to quality indicators for the management of gout and asymptomatic hyperuricaemia: results from the UK General Practice Research Database (GPRD). Mikuls T R,Farrar J T,Bilker W B,Fernandes S,Saag K G Rheumatology (Oxford, England) OBJECTIVES:: To examine adherence to validated quality indicators assessing the quality of allopurinol use in the treatment of gout and asymptomatic hyperuricaemia. METHODS:We determined physician adherence in the UK General Practice Research Database (GPRD) to three validated quality indicators developed to assess the quality of allopurinol prescribing practices. These indicators were developed to assess: (i) dosing in renal impairment; (ii) concomitant use with azathioprine or 6-mercaptopurine; and (iii) use in the treatment of asymptomatic hyperuricaemia. We also examined the association of patient-level factors (sociodemographics, comorbidity, follow-up duration and concomitant medicine use) with the treatment of asymptomatic hyperuricaemia using multivariable logistic regression. RESULTS:Of the 63 105 gout patients, 185 (0.3%) were eligible for Quality Indicator 1 and 52 (0.1%) were eligible for Quality Indicator 2. There were an additional 471 patients with asymptomatic hyperuricaemia eligible for Quality Indicator 3. Rates of practice deviation for the three individual quality indicators ranged from 25 to 57%. Male sex, older age, a history of chronic renal failure, and a greater number of concomitant medications were significantly associated with increased odds of inappropriate treatment for asymptomatic hyperuricaemia. Hypertension and diuretic use were associated with lower odds of this practice. CONCLUSIONS:One-quarter to one-half of all patients eligible for at least one of the validated quality of care indicators were subject to possible allopurinol prescribing error, suggesting that inappropriate prescribing practices are widespread with this agent. Future interventions aimed at reducing inappropriate allopurinol use are needed and should be targeted towards high-risk groups, including older men and those receiving multiple concomitant medications. 10.1093/rheumatology/keh679
    Folic acid: the solution for treating asymptomatic hyperuricemia? Scheepers Lieke Ejm The American journal of clinical nutrition 10.3945/ajcn.117.154294
    Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements. Li Qianrui,Li Xiaodan,Wang Jing,Liu Hongdie,Kwong Joey Sum-Wing,Chen Hao,Li Ling,Chung Sheng-Chia,Shah Anoop,Chen Yaolong,An Zhenmei,Sun Xin,Hemingway Harry,Tian Haoming,Li Sheyu BMJ open OBJECTIVES:Despite the publication of hundreds of trials on gout and hyperuricemia, management of these conditions remains suboptimal. We aimed to assess the quality and consistency of guidance documents for gout and hyperuricemia. DESIGN:Systematic review and quality assessment using the appraisal of guidelines for research and evaluation (AGREE) II methodology. DATA SOURCES:PubMed and EMBASE (27 October 2016), two Chinese academic databases, eight guideline databases, and Google and Google scholar (July 2017). ELIGIBILITY CRITERIA:We included the latest version of international and national/regional clinical practice guidelines and consensus statements for diagnosis and/or treatment of hyperuricemia and gout, published in English or Chinese. DATA EXTRACTION AND SYNTHESIS:Two reviewers independently screened searched items and extracted data. Four reviewers independently scored documents using AGREE II. Recommendations from all documents were tabulated and visualised in a coloured grid. RESULTS:Twenty-four guidance documents (16 clinical practice guidelines and 8 consensus statements) published between 2003 and 2017 were included. Included documents performed well in the domains of scope and purpose (median 85.4%, range 66.7%-100.0%) and clarity of presentation (median 79.2%, range 48.6%-98.6%), but unsatisfactory in applicability (median 10.9%, range 0.0%-66.7%) and editorial independence (median 28.1%, range 0.0%-83.3%). The 2017 British Society of Rheumatology guideline received the highest scores. Recommendations were concordant on the target serum uric acid level for long-term control, on some indications for urate-lowering therapy (ULT), and on the first-line drugs for ULT and for acute attack. Substantially inconsistent recommendations were provided for many items, especially for the timing of initiation of ULT and for treatment for asymptomatic hyperuricemia. CONCLUSIONS:Methodological quality needs improvement in guidance documents on gout and hyperuricemia. Evidence for certain clinical questions is lacking, despite numerous trials in this field. Promoting standard guidance development methods and synthesising high-quality clinical evidence are potential approaches to reduce recommendation inconsistencies. PROSPERO REGISTRATION NUMBER:CRD42016046104. 10.1136/bmjopen-2018-026677
    Plasma profiling of amino acids distinguishes acute gout from asymptomatic hyperuricemia. Luo Ying,Wang Ling,Liu Xin-Ying,Chen Xiaolong,Song Ya-Xiang,Li Xin-Hua,Jiang Cizong,Peng Ai,Liu Jun-Yan Amino acids Gout and hyperuricemia are highly prevalent metabolic diseases caused by high level of uric acid. Amino acids (AAs) involve in various biochemical processes including the biosynthesis of uric acid. However, the role of AAs in discriminating gout from hyperuricemia remains unknown. Here, we report that the plasma AAs profile can distinguish acute gout (AG) from asymptomatic hyperuricemia (AHU). We established an LC-MS/MS-based method to measure the plasma AAs without derivatization for the AG and AHU patients, and healthy controls. We found that the plasma profiling of AAs separated the AG patients from AHU patients and controls visually in both principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA) models. In addition, L-isoleucine, L-lysine, and L-alanine were suggested as the key mediators to distinguish the AG patients from AHU and control groups based on the S-plot analysis and variable importance in the projection values in the OPLS-DA models, volcano plot, and the receiver operating characteristic curves. In addition, the saturation of monosodium urate in the AA solutions at physiologically mimic status supported the changes in plasma AAs facilitating the precipitation of monosodium urate. This study suggests that L-isoleucine, L-lysine, and L-alanine could be the potential markers to distinguish the AG from AHU when the patients have similar blood levels of uric acid, providing new strategies for the prevention, treatment, and management of acute gout. 10.1007/s00726-018-2627-2
    The association between asymptomatic hyperuricemia and knee osteoarthritis: data from the third National Health and Nutrition Examination Survey. Wang S,Pillinger M H,Krasnokutsky S,Barbour K E Osteoarthritis and cartilage OBJECTIVE:In vitro and clinical studies suggest that urate may contribute to osteoarthritis (OA) risk. We tested the associations between hyperuricemia and knee OA, and examined the role of obesity, using a cross-sectional, nationally representative dataset. METHOD:National Health and Nutrition Examination Survey (NHANES) III used a multistage, stratified probability cluster design to select USA civilians from 1988 to 1994. Using NHANES III we studied adults >60 years, with or without hyperuricemia (serum urate > 6.8 mg/dL), excluding individuals with gout (i.e., limiting to asymptomatic hyperuricemia (AH)). Radiographic knee OA (RKOA) was defined as Kellgren-Lawrence grade ≥ 2 in any knee, and symptomatic radiographic knee osteoarthritis (RKOA) (sRKOA) was defined as RKOA plus knee pain (most days for 6 weeks) in the same knee. RESULTS:AH prevalence was 17.9% (confidence interval (CI) 15.3-20.5). RKOA prevalence was 37.7% overall (CI 35.0-40.3), and was 44.0% for AH vs 36.3% for normouricemic adults (p = 0.056). symptomatic radiographic knee osteoarthritis (sRKOA) was more prevalent in AH vs normouricemic adults (17.4% vs 10.9%, p = 0.046). In multivariate models adjusting for obesity, model-based associations between AH and knee OA were attenuated (for RKOA, prevalence ratio (PR) = 1.14, 95% CI 0.95, 1.36; for sRKOA, PR = 1.40, 95% CI 0.98, 2.01). In stratified multivariate analyses, AH was associated with sRKOA in adults without obesity (PR = 1.66, 95% CI 1.02, 2.71) but not adults with obesity (PR = 1.21, 95% CI 0.66, 2.23). CONCLUSIONS:Among adults aged 60 or older, AH is associated with knee OA risk that is more apparent in adults without obesity. 10.1016/j.joca.2019.05.013
    Asymptomatic Hyperuricemia Without Comorbidities Predicts Cardiometabolic Diseases: Five-Year Japanese Cohort Study. Kuwabara Masanari,Niwa Koichiro,Hisatome Ichiro,Nakagawa Takahiko,Roncal-Jimenez Carlos A,Andres-Hernando Ana,Bjornstad Petter,Jensen Thomas,Sato Yuka,Milagres Tamara,Garcia Gabriela,Ohno Minoru,Lanaspa Miguel A,Johnson Richard J Hypertension (Dallas, Tex. : 1979) Whether asymptomatic hyperuricemia in the absence of comorbidities increases the risk for cardiometabolic disorders and chronic kidney disease remains controversial. This study was conducted to clarify the association between asymptomatic hyperuricemia and cardiometabolic conditions. Subjects consisting of Japanese adults between 30 and 85 years of age were enrolled in the study at Center for Preventive Medicine, St Luke's International Hospital, Tokyo, and were available at enrollment (2004) and at 5-year follow-up (2009). Subjects were excluded if they were overweight or obese, hypertensive, diabetic, and dyslipidemic, had a history of gout or hyperuricemia on medications, or had chronic kidney disease as estimated glomerular filtration rate <60 mL/min per 1.73 m Linear and logistic regression analyses were used to examine the relationship between hyperuricemia and development of hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, and overweight/obesity (unadjusted and adjusted for age, sex, smoking, drinking habits, baseline estimated glomerular filtration rate, and body mass index). Five thousand eight hundred and ninety-nine subjects without comorbidities (mean age of 47±10 years, 1864 men) were followed for 5 years. Hyperuricemia (defined as >7 mg/dL in men and ≥6 mg/dL in women) was associated with increased cumulative incidence of hypertension (14.9% versus 6.1%; <0.001), dyslipidemia (23.1% versus 15.5%; <0.001), chronic kidney disease (19.0% versus 10.7%; <0.001), and overweight/obesity (8.9% versus 3.0%; <0.001), while diabetes mellitus (1.7% versus 0.9%; =0.087) showed a trend but did not reach statistical significance. In conclusion, asymptomatic hyperuricemia carries a significant risk for developing cardiometabolic conditions in Japanese individual without comorbidities. 10.1161/HYPERTENSIONAHA.116.08998
    Effects of Uric Acid on Diabetes Mellitus and Its Chronic Complications. Xiong Qing,Liu Jie,Xu Yancheng International journal of endocrinology With the deepening of the researches on uric acid, especially in the study of metabolic diseases, uric acid has been found to be closely related to obesity, metabolic syndrome, nonalcoholic fatty liver disease, diabetes, and other metabolic diseases. Uric acid causes a series of pathophysiological changes through inflammation, oxidative stress, vascular endothelial injury, and so on and thus subsequently promotes the occurrence and development of diseases. This review confirmed the positive correlation between uric acid and diabetes mellitus and its chronic complications through the pathogenesis and clinical studies aspects. 10.1155/2019/9691345
    Serum uric acid as a risk factor of all-cause mortality and cardiovascular events among type 2 diabetes population: Meta-analysis of correlational evidence. Shao Yixue,Shao Hui,Sawhney Monika S,Shi Lizheng Journal of diabetes and its complications AIMS:To explore the association between serum uric acid (SUA) level and the risk of cardiovascular complications and all-cause mortality rates among individuals with type 2 diabetes. METHODS:Web of Science and PubMed database were searched for studies reported associations between SUA level and cardiovascular complications and all-cause mortality among individuals with type 2 diabetes. Hazard ratios (HRs) were independently extracted by two investigators and synthesized through meta-analysis across selected studies. RESULTS:6 (n = 11,750 patients), 4 (n = 3044 patients) and 2 studies (n = 7792 patients) were identified reporting associations between SUA level and all-cause mortality, coronary heart disease (CHD) and stroke respectively. HR for all-cause mortality, CHD, and stroke per 59 μmol/l increase was 1.06 (95% CI: 1.03, 1.09), 1.09 (95% CI: 0.94, 1.26) and 1.19 (95% CI: 1.08, 1.31), respectively. CONCLUSIONS:Overall, the SUA level was associated with a higher risk of all-cause mortality and stroke. We found no significant association between SUA level and CHD among type 2 diabetes population. 10.1016/j.jdiacomp.2019.07.006
    Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies. Li Xue,Meng Xiangrui,Timofeeva Maria,Tzoulaki Ioanna,Tsilidis Konstantinos K,Ioannidis John PA,Campbell Harry,Theodoratou Evropi BMJ (Clinical research ed.)  To map the diverse health outcomes associated with serum uric acid (SUA) levels. Umbrella review. Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references. Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes. 57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10, 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies. Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis. 10.1136/bmj.j2376
    Effects of serum uric acid on blood-pressure lowering treatment. Grassi Guido Current medical research and opinion If hyperuricemia is an independent risk factor in blood-pressure control, urate-lowering therapy should be used to reduce cardiovascular risk. It may also act as a prognostic marker of other abnormalities. This review presents current evidence on the relationship between hyperuricemia and hypertension. 10.1080/03007995.2017.1378520
    Serum uric acid levels and risk of prehypertension: a meta-analysis. Jiang Menglin,Gong Dandan,Fan Yu Clinical chemistry and laboratory medicine Elevated serum uric acid (SUA) levels may increase the risk of prehypertension. However, the findings from these studies remain conflicting. The objective of this study was to determine the relationship between SUA levels and risk of prehypertension by conducting a meta-analysis. We conducted a comprehensive literature search of PubMed, Embase, China National Knowledge Infrastructure, VIP, and the Wangfang database without language restrictions through May 2015. Observational studies assessing the relationship between SUA levels and prevalence of prehypertension were included. Pooled adjust odds ratio (OR) and corresponding 95% confidence intervals (CI) of prehypertension were calculated for the highest vs. lowest SUA levels. Prehypertension was defined as systolic blood pressure (BP) ranging from 120 to 139 mmHg or diastolic BP ranging from 80 to 89 mmHg. Eight cross-sectional studies with a total of 21,832 prehypertensive individuals were included. Meta-analysis showed that elevated SUA levels were associated with increased risk of prehypertension (OR: 1.84; 95% CI: 1.42-2.38) comparing the highest vs. lowest level of SUA levels. Subgroup analyses showed that elevated SUA levels significantly increased the risk of prehypertension among men (OR: 1.60; 95% CI: 1.12-2.21) and women (OR: 1.59; 95% CI: 1.17-2.16). Elevated SUA levels are positively associated with the risk of prehypertension in the general population. However, more well-designed longitudinal studies are needed before a definitive conclusion can be drawn due to the cross-sectional studies included are susceptible to bias. 10.1515/cclm-2016-0339
    Effect of Uric Acid on Blood Glucose Levels. Wardhana Wardhana,Rudijanto Achmad Acta medica Indonesiana Uric acid as the final result of purine bases metabolism. In high level condition, uric acid enters the cell and act as oxidant, and acts as independent risk factor and predicts the incident of type 2 diabetes mellitus (T2DM). It may directly inactivate or through oxidative reaction that lower the nitric oxide (NO) level. Lower NO level will reduce insulin uptake in tissues and reduce in GLUT4 translocation in cell that will effect the blood glucose level. The High level of uric acid or hyperuricemia makes oxidative stress by inducing the production of reactive oxygen species (ROS) which interferes the insulin signalling pathway,creates inflammatory  state that reduced the insulin sensitivity,blood glucose uptake and metabolism, also reducing the insulin production from pancreatic islet cells.
    Asymptomatic hyperuricaemia: a silent activator of the innate immune system. Joosten Leo A B,Crişan Tania O,Bjornstad Petter,Johnson Richard J Nature reviews. Rheumatology Asymptomatic hyperuricaemia affects ~20% of the general population in the USA, with variable rates in other countries. Historically, asymptomatic hyperuricaemia was considered a benign laboratory finding with little clinical importance in the absence of gout or kidney stones. Yet, increasing evidence suggests that asymptomatic hyperuricaemia can predict the development of hypertension, obesity, diabetes mellitus and chronic kidney disease and might contribute to disease by stimulating inflammation. Although urate has been classically viewed as an antioxidant with beneficial effects, new data suggest that both crystalline and soluble urate activate various pro-inflammatory pathways. This Review summarizes what is known about the role of urate in the inflammatory response. Further research is needed to define the role of asymptomatic hyperuricaemia in these pro-inflammatory pathways. 10.1038/s41584-019-0334-3
    An update on the genetics of hyperuricaemia and gout. Major Tanya J,Dalbeth Nicola,Stahl Eli A,Merriman Tony R Nature reviews. Rheumatology A central aspect of the pathogenesis of gout is elevated urate concentrations, which lead to the formation of monosodium urate crystals. The clinical features of gout result from an individual's immune response to these deposited crystals. Genome-wide association studies (GWAS) have confirmed the importance of urate excretion in the control of serum urate levels and the risk of gout and have identified the kidneys, the gut and the liver as sites of urate regulation. The genetic contribution to the progression from hyperuricaemia to gout remains relatively poorly understood, although genes encoding proteins that are involved in the NLRP3 (NOD-, LRR- and pyrin domain-containing 3) inflammasome pathway play a part. Genome-wide and targeted sequencing is beginning to identify uncommon population-specific variants that are associated with urate levels and gout. Mendelian randomization studies using urate-associated genetic variants as unconfounded surrogates for lifelong urate exposure have not supported claims that urate is causal for metabolic conditions that are comorbidities of hyperuricaemia and gout. Genetic studies have also identified genetic variants that predict responsiveness to therapies (for example, urate-lowering drugs) for treatment of hyperuricaemia. Future research should focus on large GWAS (that include asymptomatic hyperuricaemic individuals) and on increasing the use of whole-genome sequencing data to identify uncommon genetic variants with increased penetrance that might provide opportunities for clinical translation. 10.1038/s41584-018-0004-x
    Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout. Kawamura Yusuke,Nakaoka Hirofumi,Nakayama Akiyoshi,Okada Yukinori,Yamamoto Ken,Higashino Toshihide,Sakiyama Masayuki,Shimizu Toru,Ooyama Hiroshi,Ooyama Keiko,Nagase Mitsuo,Hidaka Yuji,Shirahama Yuko,Hosomichi Kazuyoshi,Nishida Yuichiro,Shimoshikiryo Ippei,Hishida Asahi,Katsuura-Kamano Sakurako,Shimizu Seiko,Kawaguchi Makoto,Uemura Hirokazu,Ibusuki Rie,Hara Megumi,Naito Mariko,Takao Mikiya,Nakajima Mayuko,Iwasawa Satoko,Nakashima Hiroshi,Ohnaka Keizo,Nakamura Takahiro,Stiburkova Blanka,Merriman Tony R,Nakatochi Masahiro,Ichihara Sahoko,Yokota Mitsuhiro,Takada Tappei,Saitoh Tatsuya,Kamatani Yoichiro,Takahashi Atsushi,Arisawa Kokichi,Takezaki Toshiro,Tanaka Keitaro,Wakai Kenji,Kubo Michiaki,Hosoya Tatsuo,Ichida Kimiyoshi,Inoue Ituro,Shinomiya Nariyoshi,Matsuo Hirotaka Annals of the rheumatic diseases OBJECTIVE:The first ever genome-wide association study (GWAS) of clinically defined gout cases and asymptomatic hyperuricaemia (AHUA) controls was performed to identify novel gout loci that aggravate AHUA into gout. METHODS:We carried out a GWAS of 945 clinically defined gout cases and 1003 AHUA controls followed by 2 replication studies. In total, 2860 gout cases and 3149 AHUA controls (all Japanese men) were analysed. We also compared the ORs for each locus in the present GWAS (gout vs AHUA) with those in the previous GWAS (gout vs normouricaemia). RESULTS:This new approach enabled us to identify two novel gout loci (rs7927466 of and rs9952962 of ) and one suggestive locus (rs12980365 of ) at the genome-wide significance level (p<5.0×10 ). The present study also identified the loci of , and . One of them, rs671 of , was identified as a gout locus by GWAS for the first time. Comparing ORs for each locus in the present versus the previous GWAS revealed three 'gout vs AHUA GWAS'-specific loci (, and ) to be clearly associated with mechanisms of gout development which distinctly differ from the known gout risk loci that basically elevate serum uric acid level. CONCLUSIONS:This meta-analysis is the first to reveal the loci associated with crystal-induced inflammation, the last step in gout development that aggravates AHUA into gout. Our findings should help to elucidate the molecular mechanisms of gout development and assist the prevention of gout attacks in high-risk AHUA individuals. 10.1136/annrheumdis-2019-215521
    Increased urinary glucose excretion is associated with a reduced risk of hyperuricaemia. Chen J,Qiu S-H,Guo H-J,Li W,Sun Z-L Diabetic medicine : a journal of the British Diabetic Association AIM:To investigate the association of urinary glucose excretion with levels of serum uric acid in adults with newly diagnosed diabetes. METHODS:A total of 597 people with newly diagnosed diabetes, confirmed in an oral glucose tolerance test, were included in the present study. The participants were divided into two groups: 142 participants with low urinary glucose excretion and 455 with high urinary glucose excretion. Demographic characteristics and clinical variables were evaluated. The association of urinary glucose excretion with uric acid was analysed using multivariable regression analysis. RESULTS:The low urinary glucose excretion group had a significantly higher prevalence of hyperuricaemia than the high urinary glucose excretion group. Moreover, urinary glucose excretion was negatively associated with uric acid level. The correlation remained significant after adjusting for potential confounders, including gender, age, fasting plasma glucose, 2-h plasma glucose and BMI. The results also showed that participants with high urinary glucose excretion were at decreased risk of hyperuricaemia (odds ratio 0.47, 95% CI 0.27-0.80; P = 0.006). CONCLUSION:Urinary glucose excretion was independently associated with uric acid level in participants with newly diagnosed diabetes. In addition to lowering blood glucose, promoting urinary glucose excretion may also be an effective approach to reducing serum uric acid levels, especially for people with diabetes complicated with hyperuricaemia. 10.1111/dme.13956
    Clinical characteristics of patients under 40 years old with early-onset hyperuricaemia: a retrospective monocentric study in China. Zhang Yi,Yang Yong,Xue Leixi,Wen Jian,Bo Lin,Tang Mei,Yang Ru,Yan Dong,Liu Zhichun BMJ open OBJECTIVE:To investigate the clinical characteristics of patients with early-onset hyperuricaemia (HUC). METHODS:A retrospective study using data from the Second Affiliated Hospital of Soochow University was conducted. 623 patients with HUC were divided into early-onset group and late-onset group. Another 201 healthy subjects ≤40 years old were regarded as control group. The data of physical measurements and biochemistry test were collected. Clinical data of early-onset group were compared with late-onset group and control group by analysis of variance (ANOVA) and χ test. Principal component analysis (PCA) was applied. Logistic regression was used to identify the clinical factors correlated with patients with early-onset HUC. RESULTS:The patients of early-onset group had different body mass index (BMI), serum albumin, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), gamma-glutamyltransferase (GGT), creatinine (Cr), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), TG/high density lipoprotein (HDL) ratio, HDL and percentage of males, hypertension (HBP) as well as fatty liver compared with healthy people in the control group. Early-onset group patients had different albumin, ALT, fasting blood glucose, Cr, percentage of males and HBP compared with late-onset group patients. PCA identified four significant patterns including PC1 (labelled 'TG and HDL'), PC2 (labelled 'fatty liver and liver enzymes'), PC3 (labelled 'TC and LDL') and PC4 (labelled 'AKP'). The results of univariate and multivariate logistic regression analysis showed that BMI, HBP and albumin were correlative factors for early onset of HUC when the patients with early-onset and late-onset HUC were involved, while gender, BMI, PC1, PC2 and PC4 were correlative factors for early-onset HUC when the early-onset and control groups were involved. CONCLUSION:This study described a group of patients with early-onset HUC with distinct clinical features. Gender, BMI, 'TG and HDL', 'fatty liver and liver enzymes' and 'AKP' have higher values than HBP, type 2 diabetes mellitus and 'TC and LDL' in patients under 40 years old with early-onset HUC. 10.1136/bmjopen-2018-025528
    The effects of fruit consumption in patients with hyperuricaemia or gout. Nakagawa Takahiko,Lanaspa Miguel A,Johnson Richard J Rheumatology (Oxford, England) The consumption of fructose has gained increased attention as a potential cause of hyperuricaemia since fructose metabolism produces urate as a byproduct. In addition to sucrose and high fructose corn syrup, fresh fruits also contain fructose, suggesting that patients with hyperuricaemia or gout might also avoid fresh fruit. However, the effect of fruits is complex. Some studies reported that fruit intake was associated with gout flares while other studies showed that fruits rather lowered the risk for gout. Thus, fruits should not be simply viewed as a source of fructose. The complexity of fruits is accounted for by several nutrients existing in fruits. Vitamin C, epicatechin, flavonols, potassium and fibre are all nutrients in fruits, and these factors could modify fructose and urate effects. In this review, we discuss clinical studies evaluating the effect of fruit and fruit juice intake on hyperuricaemia and gout, and propose potential mechanisms for how fruit may influence urate levels. 10.1093/rheumatology/kez128
    Prevalence and associations of gout and hyperuricaemia: results from an Australian population-based study. Ting K,Gill T K,Keen H,Tucker G R,Hill C L Internal medicine journal BACKGROUND:Despite gout and hyperuricaemia being major comorbid health issues worldwide, there is a knowledge gap regarding their impact in the Australian community. AIMS:To determine the prevalence and associations of self-reported medically diagnosed gout and hyperuricaemia in an Australian population-based cohort. METHODS:The North West Adelaide Health Study is a longitudinal cohort study consisting of three stages of data collection. Each stage comprised a self-complete questionnaire, clinic assessment and computer-assisted telephone interview. In Stage 3 (2008-2010), participants were asked if a doctor had ever diagnosed them with gout. Additional data included demographics, comorbidities, laboratory data and Short Form 36 (SF-36). Participants were defined as having gout if they had self-reported medically diagnosed gout or were taking any gout-specific medication (allopurinol, colchicine, probenecid). Hyperuricaemia was defined as a serum uric acid (SUA) level >0.42 mmol/L in men and >0.34 mmol/L in women. RESULTS:The overall prevalence of gout was 5.2%. Males were significantly more likely to have gout than females (8.5 vs 2.1%, P < 0.001). The overall prevalence of hyperuricaemia was 16.6%, with being male again identified as a significant risk factor (17.8 vs 15.4%, P < 0.01). Both gout and hyperuricaemia were associated with male sex, body mass index and renal disease after multivariable adjustment. There was no significant difference reported in quality of life (mean SF-36) scores in participants with gout compared to unaffected individuals. CONCLUSION:The prevalence of gout and hyperuricaemia is high in the South Australian population. This study emphasises the need for optimal diagnosis and management of gout in Australia. 10.1111/imj.13006
    Hyperuricaemia and risk of nonalcoholic fatty liver disease: A meta-analysis. Wijarnpreecha Karn,Panjawatanan Panadeekarn,Lekuthai Natasorn,Thongprayoon Charat,Cheungpasitporn Wisit,Ungprasert Patompong Liver international : official journal of the International Association for the Study of the Liver BACKGROUND:The association between hyperuricaemia and nonalcoholic fatty liver disease (NAFLD), one of the leading causes of cirrhosis worldwide, has been demonstrated in recent epidemiological studies. This meta-analysis was conducted to summarize all available data and to estimate the risk of NAFLD among subjects with hyperuricaemia. METHODS:Comprehensive literature review was conducted using MEDLINE and EMBASE database through August 2016 to identify studies that compared the risk of NAFLD among subjects with hyperuricaemia vs those with normal uric acid level. Effect estimates from individual study were extracted and combined together using random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS:Twenty-five studies met the eligibility criteria and were included in the meta-analysis. The risk of NAFLD in subjects with hyperuricaemia was significantly higher than subjects with normal uric acid level with the pooled odds ratio (OR) of 1.97 (95% confidence interval (CI), 1.69-2.29). The heterogeneity between studies of the overall analysis was high with an I of 87%. Subgroup analysis based on 11 studies that provided data on males subgroup and nine studies that provided data on females subgroup showed that the risk was significantly increased for both sexes with pooled OR of 1.64 (95% CI, 1.40-1.93) among males and pooled OR of 2.21 (95% CI, 1.85-2.64) among females. CONCLUSIONS:A significantly increased risk of NAFLD among patients with hyperuricaemia was demonstrated in this meta-analysis. Further studies are required to establish the role of uric acid in the pathogenesis of NAFLD. 10.1111/liv.13329
    Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout. Bursill David,Taylor William J,Terkeltaub Robert,Abhishek Abhishek,So Alexander K,Vargas-Santos Ana Beatriz,Gaffo Angelo Lino,Rosenthal Ann,Tausche Anne-Kathrin,Reginato Anthony,Manger Bernhard,Sciré Carlo,Pineda Carlos,van Durme Caroline,Lin Ching-Tsai,Yin Congcong,Albert Daniel Arthur,Biernat-Kaluza Edyta,Roddy Edward,Pascual Eliseo,Becce Fabio,Perez-Ruiz Fernando,Sivera Francisca,Lioté Frédéric,Schett Georg,Nuki George,Filippou Georgios,McCarthy Geraldine,da Rocha Castelar Pinheiro Geraldo,Ea Hang-Korng,Tupinambá Helena De Almeida,Yamanaka Hisashi,Choi Hyon K,Mackay James,ODell James R,Vázquez Mellado Janitzia,Singh Jasvinder A,Fitzgerald John D,Jacobsson Lennart T H,Joosten Leo,Harrold Leslie R,Stamp Lisa,Andrés Mariano,Gutierrez Marwin,Kuwabara Masanari,Dehlin Mats,Janssen Matthijs,Doherty Michael,Hershfield Michael S,Pillinger Michael,Edwards N Lawrence,Schlesinger Naomi,Kumar Nitin,Slot Ole,Ottaviani Sebastien,Richette Pascal,MacMullan Paul A,Chapman Peter T,Lipsky Peter E,Robinson Philip,Khanna Puja P,Gancheva Rada N,Grainger Rebecca,Johnson Richard J,Te Kampe Ritch,Keenan Robert T,Tedeschi Sara K,Kim Seoyoung,Choi Sung Jae,Fields Theodore R,Bardin Thomas,Uhlig Till,Jansen Tim,Merriman Tony,Pascart Tristan,Neogi Tuhina,Klück Viola,Louthrenoo Worawit,Dalbeth Nicola Annals of the rheumatic diseases OBJECTIVE:There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout. METHODS:A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions. RESULTS:The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus). CONCLUSION:Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice. 10.1136/annrheumdis-2019-215933
    Association between low dietary zinc and hyperuricaemia in middle-aged and older males in China: a cross-sectional study. Xie Dong-xing,Xiong Yi-lin,Zeng Chao,Wei Jie,Yang Tuo,Li Hui,Wang Yi-lun,Gao Shu-guang,Li Yu-sheng,Lei Guang-hua BMJ open OBJECTIVE:To examine the associations between dietary zinc intake and hyperuricaemia. DESIGN:Cross-sectional study. SETTING:This study was conducted in a health examination centre of China. PARTICIPANTS:A total of 5168 middle-aged and older participants (aged 40 years or above) (2697 men and 2471 women) were included. OUTCOME MEASURES:Dietary zinc intake was assessed using a validated semiquantitative food frequency questionnaire. Hyperuricaemia was defined as uric acid ≥416 µmol/L for males and ≥360 µmol/L for females. RESULTS:For males, the prevalence of hyperuricaemia was 22.9%. After adjusting for age, body mass index (BMI) and energy intake, the ORs were 0.68 (95% CI 0.45 to 0.92) in the second quintile, 0.63 (95% CI 0.45 to 0.89) in the third quintile, 0.68 (95% CI 0.46 to 1.00) in the fourth quintile and 0.55 (95% CI 0.35 to 0.87) in the fifth quintile comparing the lowest quintile of Zn intake, respectively (p for trend=0.03). In the multivariable adjusted model, the relative odds of hyperuricaemia were significantly decreased by 0.71 times in the second quintile of zinc intake (OR 0.71, 95% CI 0.52 to 0.98), 0.64 times in the third quintile (OR 0.65, 95% CI 0.44 to 0.94) and 0.55 times in the fifth quintile (OR 0.56, 95% CI 0.32 to 0.97) compared with those in the lowest quintile, and p for trend was 0.064. For females, the prevalence of hyperuricaemia was 10.0%, and unadjusted, minimally adjusted as well as multivariable adjusted ORs all suggested no significant association between dietary zinc intake and hyperuricaemia. CONCLUSIONS:The findings of this cross-sectional study indicated that dietary zinc intake was inversely associated with hyperuricaemia in middle-aged and older males, but not in females. The association was significant after considering the influence of age, BMI and energy intake, and after that, minimum adjustment remained independent of further confounding factors such as vitamin C intake, alcohol drinking status and nutrient supplementation. 10.1136/bmjopen-2015-008637
    Pharmacotherapy for hyperuricaemia in hypertensive patients. Gois Pedro Henrique França,Souza Edison Regio de Moraes The Cochrane database of systematic reviews BACKGROUND:This is the second update of this systematic review. High blood pressure represents a major public health problem. Worldwide, approximately one-fourth of the adult population has hypertension. Epidemiological and experimental studies suggest a link between hyperuricaemia and hypertension. Hyperuricaemia affects 25% to 40% of those with untreated hypertension; a much lower prevalence has been reported in those with normotension or in the general population. However, whether lowering serum uric acid (UA) might lower blood pressure (BP), is an unanswered question. OBJECTIVES:To determine whether UA-lowering agents reduce BP in people with primary hypertension or prehypertension, compared with placebo. SEARCH METHODS:The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to May 2020: the Cochrane Hypertension Specialised Register, CENTRAL 2018, Issue 12, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched LILACS (1982 to May 2020), and contacted authors of relevant papers regarding further published and unpublished work. The searches had no language or date restrictions. SELECTION CRITERIA:To be included in this updated review, the studies had to meet the following criteria: 1) randomised or quasi-randomised, with a group assigned to receive a UA-lowering agent and another group assigned to receive placebo; 2) double-blind, single-blind, or open-label; 3) parallel or cross-over trial design; 4) cross-over trials had to have a washout period of at least two weeks; 5) minimum treatment duration of four weeks; 6) participants had to have a diagnosis of essential hypertension or prehypertension plus hyperuricaemia (serum UA greater than 6 mg/dL in women, 7 mg/dL in men, and 5.5 mg/dL in children or adolescents); 7) outcome measures included change in 24-hour ambulatory systolic or diastolic BP, or both; or clinic-measured systolic or diastolic BP, or both. DATA COLLECTION AND ANALYSIS:The two review authors independently collected the data using a data extraction form, and resolved any disagreements via discussion. We assessed risk of bias using the Cochrane 'Risk of bias' tool. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS:In this review update, we screened 722 records, selected 26 full-text reports for evaluation. We identified no ongoing studies and did not add any new studies. We included three randomised controlled trials (RCTs), enrolling 211 people with hypertension or prehypertension, plus hyperuricaemia. Low-certainty evidence from three RCTs found inconclusive results between those who received UA-lowering drugs and placebo, in 24-hour ambulatory systolic (MD -6.2 mmHg, 95% CI -12.8 to 0.5) or diastolic BP (-3.9 mmHg, 95% CI -9.2 to 1.4). Low-certainty evidence from two RCTs found that UA-lowering drugs reduced clinic-measured systolic BP (-8.43 mmHg, 95% CI -15.24 to -1.62) but results for clinic-measured diastolic BP were inconclusive (-6.45 mmHg, 95% CI -13.60 to 0.70). High-certainty evidence from three RCTs found that serum UA levels were reduced by 3.1 mg/dL (95% CI 2.4 to 3.8) in the participants that received UA-lowering drugs. Low-certainty evidence from three RCTs found inconclusive results regarding the occurrence of adverse events between those who received UA-lowering drugs and placebo (RR 1.86, 95% CI 0.43 to 8.10). AUTHORS' CONCLUSIONS:In this updated Cochrane Review, the current RCT data are insufficient to know whether UA-lowering therapy lowers BP. More studies are needed. 10.1002/14651858.CD008652.pub4
    Temporal trends in hyperuricaemia in the Irish health system from 2006-2014: A cohort study. Kumar A U Arun,Browne Leonard D,Li Xia,Adeeb Fahd,Perez-Ruiz Fernando,Fraser Alexander D,Stack Austin G PloS one BACKGROUND:Elevated serum uric acid (sUA) concentrations are common in the general population and are associated with chronic metabolic conditions and adverse clinical outcomes. We evaluated secular trends in the burden of hyperuricaemia from 2006-2014 within the Irish health system. METHODS:Data from the National Kidney Disease Surveillance Programme was used to determine the prevalence of elevated sUA in adults, age > 18 years, within the Irish health system. Hyperuricaemia was defined as sUA > 416.4 μmol/L in men and > 339.06 μmol/L in women, and prevalence was calculated as the proportion of patients per year with mean sUA levels above sex-specific thresholds. Temporal trends in prevalence were compared from 2006 to 2014 while general estimating equations (GEE) explored variation across calendar years expressed as odds ratios (OR) and 95% Confidence intervals (CI). RESULTS:From 2006 to 2014, prevalence of hyperuricaemia increased from 19.7% to 25.0% in men and from 20.5% to 24.1% in women, P<0.001. The corresponding sUA concentrations increased significantly from 314.6 (93.9) in 2006 to 325.6 (96.2) in 2014, P<0.001. Age-specific prevalence increased in all groups from 2006 to 2014, and the magnitude of increase was similar for each age category. Adjusting for baseline demographic characteristics and illness indicators, the likelihood of hyperuricemia was greatest for patients in 2014; OR 1.45 (1.26-1.65) for men and OR 1.47 (1.29-1.67) in women vs 2006 (referent). Factors associated with hyperuricaemia included: worsening kidney function, elevated white cell count, raised serum phosphate and calcium levels, elevated total protein and higher haemoglobin concentrations, all P<0.001. CONCLUSIONS:The burden of hyperuricaemia is substantial in the Irish health system and has increased in frequency over the past decade. Advancing age, poorer kidney function, measures of nutrition and inflammation, and regional variation all contribute to increasing prevalence, but these do not fully explain emerging trends. 10.1371/journal.pone.0198197
    Gout and hyperuricaemia in the USA: prevalence and trends. Singh Gurkirpal,Lingala Bharathi,Mithal Alka Rheumatology (Oxford, England) OBJECTIVES:Several recent observations have suggested that the prevalence of gout may be increasing worldwide, but there are no recent data from the USA. We analysed the prevalence of hyperuricaemia and gout in the US population from 2007-08 to 2015-16. METHODS:We studied adults ⩾20 years of age from the National Health and Nutrition Examination Survey from 2007-08 to 2015-16. Persons with gout were identified from the home interview question 'Has a doctor or other health professional ever told you that you had gout?' Hyperuricaemia was defined as a serum urate level >0.40 mmol/l (6.8 mg/dl) (supersaturation levels at physiological temperatures and pH). RESULTS:In 2015-16, the overall prevalence of gout among US adults was 3.9%, corresponding to a total affected population of 9.2 million. Hyperuricaemia (>0.40 mmol/l or 6.8 mg/dl) was seen in 14.6% of the US population (estimated 32.5 million individuals). No significant trends were identified in the age-adjusted prevalence of gout and hyperuricaemia. Statistical comparisons between 2007-08 and 2015-16 age-adjusted rates were not significant. CONCLUSION:While the age-adjusted prevalence of gout and hyperuricaemia has remained unchanged in the most recent decade from 2007-08 to 2015-16, the estimated total number of persons with self-reported gout has increased from 8.3 million to 9.2 million. The age-adjusted prevalence of hyperuricaemia has declined slightly, but the total number of affected individuals is virtually identical (32.5 million in 2015-16 compared with 32.1 million in 2007-08). 10.1093/rheumatology/kez196
    How should we manage asymptomatic hyperuricemia? Chalès Gérard Joint bone spine The definition of asymptomatic hyperuricemia remains unclear, as no consensus exists about the serum urate cutoff or the relevance of ultrasound findings. Comorbidities associated with hyperuricemia have increased in frequency over the past two decades. Hyperuricemia (and/or gout) may be a cause or a consequence of a comorbidity. Whereas epidemiological studies suggest that hyperuricemia may be linked to cardiovascular, metabolic, and renal comorbidities, Mendelian randomization studies have not provided proof that these links are causal. Discrepancies between findings from observational studies and clinical trials preclude the development of recommendations about the potential benefits of urate-lowering therapy (ULT) in individual patients with asymptomatic hyperuricemia. The risk/benefit ratio of ULT is unclear. The risk of developing gout, estimated at 50%, must be weighed against the risk of cutaneous and cardiovascular side effects of xanthine oxidase inhibitors. The need for optimal comorbidity management, in contrast, is universally accepted. Medications for comorbidities that elevate urate levels should be discontinued and replaced with medications that have the opposite effect. Therapeutic lifestyle changes, weight loss as appropriate, and sufficient physical activity are useful for improving general health. Whether ULT has beneficial effects on comorbidities will be known only when well-powered interventional trials with relevant primary endpoints are available. 10.1016/j.jbspin.2018.10.004
    Asymptomatic hyperuricemia: is it really asymptomatic? Yip Kevin,Cohen Rebecca E,Pillinger Michael H Current opinion in rheumatology PURPOSE OF REVIEW:Hyperuricemia is highly prevalent, affecting approximately 38 million individuals in the United States. However, the significance of asymptomatic hyperuricemia - hyperuricemia in the absence of gout - continues to be debated. RECENT FINDINGS:Asymptomatic hyperuricemia results in monosodium urate crystal deposition in tissues, which may promote chronic inflammation. Intracellularly, hyperuricemia inhibits the master regulator adenosine monophosphate (AMP)-associated protein kinase and may condition innate immune responses through durable epigenetic modifications. At the population level, asymptomatic hyperuricemia is associated with multiple comorbidities, including hypertension, chronic kidney disease, coronary artery disease, and diabetes; limitations of these studies include that most are retrospective and some do not rigorously distinguish between asymptomatic hyperuricemia and gout. Treatment studies suggest that urate lowering may reduce the risk of incidence or progression of some of these comorbidities; unfortunately, many of these treatment studies are small or flawed, and not all study results are consistent. SUMMARY:Accumulating evidence suggests that asymptomatic hyperuricemia contributes to the comorbidities with which it associates and that proper asymptomatic hyperuricemia treatment may reduce future risk. Additional prospective trials are needed to definitely establish causality and support decision-making as to whether, and which patients with asymptomatic hyperuricemia would warrant urate-lowering treatment. 10.1097/BOR.0000000000000679
    Prevalence and discrimination of OMERACT-defined elementary ultrasound lesions of gout in people with asymptomatic hyperuricaemia: A systematic review and meta-analysis. Stewart Sarah,Maxwell Hannah,Dalbeth Nicola Seminars in arthritis and rheumatism OBJECTIVES:Ultrasound lesions of gout have been described in people with asymptomatic hyperuricemia. However, the anatomical sites and ultrasound lesions most frequently involved in asymptomatic hyperuricemia have not yet been established. This systematic review and meta-analysis aimed to determine the prevalence of the Outcome Measures in Rheumatology (OMERACT) elementary ultrasound lesions of gout (double contour, aggregates, tophus, erosion) at various sites in people with asymptomatic hyperuricemia and to determine which sites and lesions discriminate from people with normouricemia. METHODS:A systematic search of electronic databases, conference abstracts and reference lists was undertaken. Studies were included if they used ultrasound to image people with asymptomatic hyperuricemia and reported ≥1 OMERACT-defined lesion of gout. Meta-analyses were undertaken for the pooled prevalence of site-specific lesions in people with asymptomatic hyperuricemia, and the pooled odds ratios of these lesions compared to people with normouricemia. RESULTS:Twenty studies were included. The most common site scanned was the first metatarsophalangeal joint (1MTP) (n = 17 studies) and the most common lesion reported, the double contour (n = 18). Meta-analyses of pooled prevalence showed 1MTP double contour was the most frequent finding in people with asymptomatic hyperuricemia (0.31, 95% confidence interval (CI) 0.20-0.42), followed by femoral condyle double contour (0.16, 95%CI 0.08-0.24) and 1MTP tophus (0.16, 95%CI 0.03-0.29). The highest pooled odds ratios for asymptomatic hyperuricemia vs. normouricemia were 6.98 (95%CI 3.14-15.57) for 1MTP double contour, 13.67 (95%CI 5.42-34.49) for femoral condyle double contour and 6.10 (95%CI 1.55-24.04) for 1MTP tophus. CONCLUSION:In people with asymptomatic hyperuricemia, scanning of the 1MTP and femoral condyle for double contour, plus the 1MTP for tophus, has the highest prevalence and discrimination compared to those with normouricemia. 10.1016/j.semarthrit.2019.01.004
    Management of asymptomatic hyperuricemia: Integrated Diabetes & Endocrine Academy (IDEA) consensus statement. Valsaraj Rahul,Singh Awadhesh Kumar,Gangopadhyay Kalyan Kumar,Ghoshdastidar Biswajit,Goyal Ghanshyam,Batin Masood,Mukherjee Dibyendu,Sengupta Upal,Chatterjee Sanjay,Sengupta Nilanjan Diabetes & metabolic syndrome AIM:The definition and management of asymptomatic hyperuricemia has been an area of controversy for many decades. Debate persists regarding the benefit of treating all cases of asymptomatic hyperuricemia and hence, unsurprisingly there are no clear clinical practice guidelines from our country. PARTICIPANTS:Ten members consisting of eminent physicians, endocrinologists, nephrologist and a rheumatologist were selected by the Integrated Diabetes & Endocrine Academy (IDEA) for a closed meeting with the aim to come to a consensus. EVIDENCE:A literature search was performed using PubMed and Cochrane library following which published articles in indexed peer review journals were selected. CONSENSUS PROCESS:Each participant voiced their opinion after reviewing the available data and a consensus was reached after three meetings by voting. CONCLUSION:Recommendations were made on important areas such as definition, investigation and management of asymptomatic hyperuricemia. 10.1016/j.dsx.2020.01.007