Gout In People Research Articles

Efficacy and Safety of Allopurinol and Febuxostat in Patients With Gout and CKD: Subgroup Analysis of the STOP Gout Trial

Rationale & ObjectiveWe conducted a prespecified examination of the efficacy and safety of allopurinol and febuxostat administered using a treat-to-target strategy in trial participants with chronic kidney disease (CKD). Study DesignPrespecified sub cohort analysis of a randomized controlled trial. Setting& Participants: A sub study of the STOP Gout trial in participants with CKD. CKD was defined as an eGFR 30-59 mL/min/1.73 m2 at baseline. ExposureTrial participants with CKD and gout and serum urate (sUA) concentration ≥6.8 mg/dL were randomized 1:1 to receive allopurinol or febuxostat. Urate lowering therapy (ULT) was titrated during weeks 0-24 to achieve a goal sUA of <6.0 mg/dl (<5.0 mg/dl with tophi) (Phase 1) and maintained during weeks 25-48 (Phase 2). Gout flare was assessed between weeks 49-72 (Phase 3). OutcomeGout flare between weeks 49-72 (Phase 3) was the primary outcome. Secondary outcomes included sUA goal achievement and ULT dosing at end of Phase 2, and serious adverse events (SAEs). Analytical ApproachOutcomes between treatment groups were compared using logistic regression models for binary outcomes, and Poisson regression for flare rates. Multivariable models were subsequently used, adjusting for factors identified to be imbalanced by treatment arm. Results351 of 940 participants (37.3%) had CKD; 277 were assessed for the primary outcome. Fewer patients randomized to allopurinol had a flare during phase 3 (32% vs 45%; p=0.02) despite similar attainment of sUA goal (79% vs. 81%; p=0.6) by the end of Phase 2. Acute kidney injury (AKI) was more common in participants with stage 3 CKD randomized to allopurinol compared to febuxostat. LimitationsLimited power to assess infrequent safety events, largely male, older population. ConclusionsAllopurinol and febuxostat are similarly efficacious and well-tolerated in the treatment of gout in people with CKD when used in a treat-to-target regimen.

Proton pump inhibitor use associated with an increased risk of gout: A population-based case-control study.

In previous reports, proton pump inhibitor (PPI) use increased the risk of gout. However, there is no epidemiological study investigating this association. We aimed to examine the potential impact of PPI treatment on the risk of developing gout. A population-based case-control study was performed using a Longitudinal Health Insurance Database 2000 from Taiwan (population 23 million). We identified gout cases and non-gout controls through propensity score matching at 1:1, which was matched by sex and age. We used a conditional logistic regression model to estimate an odds ratio and 95% confidence intervals (CI) for gout population versus controls. Esomeprazole increased the risk of gout after adjusting confounding variables (adjusted odds ratio [aOR] 1.3; 95% CI 1.0-1.6). The risk of gout was highest within 30 days of PPI treatment (aOR 1.7; 95% CI 1.4-1.9) and attenuated thereafter. The risk of gout was increased among female users of PPI compared with male users (aOR 2.2; 95% CI 1.7-2.8). The aOR of gout in people with PPI use was higher in middle-aged individuals (41-60 years: aOR 2.1; 95% CI 1.7-2.7) than in the older group (≥60 years: aOR 1.8; 95% CI 1.5-2.2). Our findings provide population-level evidence for the hypothesis that PPI treatment is positively associated with the risk of developing gout. Further research on the mechanism underlying this association is warranted.

Sodium-glucose cotransporter 1 inhibition and gout: Mendelian randomisation study

ObjectiveSodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce serum urate, but their efficacy depends on renal function which is often impaired in people with gout. SGLT1 is primarily expressed in the small intestine and its inhibition may be a more suitable therapeutic target. We aimed to investigate the association of genetically proxied SGLT1i with gout risk, serum urate levels and cardiovascular safety using Mendelian randomisation (MR). MethodsLeveraging data from a genome-wide association study of 344,182 individuals in the UK Biobank, we identified a missense variant in the SLC5A1 gene that associated with glycated haemoglobin (HbA1c) to proxy SGLT1i. Outcome genetic data comprised 13,179 gout cases and 750,634 controls, 457,690 individuals for serum urate levels, and up to 977,323 individuals for cardiovascular safety outcomes. We applied the Wald ratio method and investigated potential genetic confounding using colocalization. ResultsThe rs17683430 missense variant was selected to instrument SGLT1i. Genetically proxied SGLT1i was associated with 75% reduction in gout risk (OR 0.25; 95%CI 0.06, 0.99; p = 0.048) and 32.0 μmol/L reduction in serum urate (95%CI −56.7, −7.3; p = 0.01), per 6.7 mmol/mol reduction in HbA1c. SGLT1i was associated with increased levels of low-density lipoprotein cholesterol (0.37 mmol/L; 95%CI 0.17, 0.56; p = 0.0002) but not risk of coronary heart disease, stroke, or chronic kidney disease. Colocalization did not suggest that results are attributable to genetic confounding. ConclusionSGLT1 inhibition may represent a novel therapeutic option for preventing gout in people with or without comorbid diabetes. Randomised trials are needed to formally investigate efficacy and safety.

Longitudinal development of incident gout from low-normal baseline serum urate concentrations: individual participant data analysis

IntroductionElevated serum urate (SU) concentration is the central risk factor for the development of gout. The aim of this study was to examine the incidence of gout in people with low and normal SU levels (< 7.00 mg/dL).MethodsLongitudinal cohort data from the Atherosclerosis Risk in Communities Study (ARIC), Coronary Artery Risk Development in Young Adults Study (CARDIA), and both the Original and Offspring cohorts of the Framingham Heart Study (FHS) were used to determine incident gout by baseline SU over 3, 5, 10, 12 and 15 year periods. A Cox proportional hazards model with covariables of age, gender, ethnicity, and cohort was calculated to report the hazard ratios (HR) for incident gout.ResultsThe incidence of gout at 15 years for a baseline SU < 4.00 mg/dL was 0.59%, 4.00–4.49 mg/dL was 1.28%, 4.50–4.99 mg/dL was 0.86%, 5.00–5.49 mg/dL was 0.94%, 5.50–5.99 mg/dL was 1.52%, 6.00–6.49 mg/dL was 2.91%, 6.50–6.99 mg/dL was 3.2%, and > 7.00 mg/dL was 12.2%. In an adjusted Cox proportional hazards model, compared to the referent baseline SU < 4.00 mg/dL, there was a non-significant increase in incident gout for baseline SU bands between 4.00–5.49 mg/dL, whereas incident gout was significantly increased for SU 5.50–5.99 mg/dL (HR 2.60), 6.00–6.49 mg/dL (HR 3.70), 6.50–6.99 mg/dL (HR 5.24) and > 7.00 mg/dL (HR 18.62).ConclusionA baseline SU of 5.50 mg/dL or more is a risk factor for development of gout over 15 years. However, incident gout does occur over time in a small proportion of people with lower baseline SU levels.

Prevalence and discrimination of OMERACT-defined elementary ultrasound lesions of gout in people with asymptomatic hyperuricaemia: A systematic review and meta-analysis

ObjectivesUltrasound 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. MethodsA 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. ResultsTwenty 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. ConclusionIn 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.

Gout and diabetes: a common combination

The aims of this cross-sectional study were to compare metabolic parameters in people with gout and diabetes with gout only and type 2 diabetes mellitus (T2DM) only. Fifty General Practices...

Hyperthyroid and hypothyroid status was strongly associated with gout and weakly associated with hyperuricaemia.

ObjectivesThe aim of this study was to estimate the risk of hyperuricaemia and gout in people with hypothyroid or hyperthyroid status.MethodsThis study analyzed data from individuals who participated in health screening programs at Chang Gung Memorial Hospital in northern Taiwan (2000–2010). Participants were categorized as having euthyroid, hypothyroid, or hyperthyroid status according to their thyroid-stimulating hormone (TSH) levels. Multinomial logistic regression models were used to calculate the odds ratios (95% CI) for hyperuricaemia and gout in participants with thyroid dysfunction compared to euthyroid participants.ResultsA total of 87,813 (euthyroid, 83,502; hypothyroid, 1,460; hyperthyroid, 2,851) participants were included. The prevalence of hyperuricaemia was higher in hyperthyroid subjects (19.4%) than in euthyroid subjects (17.8%) but not in hypothyroid subjects (19.3%). The prevalence of gout was significantly higher in both hypothyroid (6.0%) and hyperthyroid (5.3%) subjects than in euthyroid subjects (4.3%). In men, hypothyroid or hyperthyroid status was not associated with hyperuricaemia. However, hypothyroid or hyperthyroid status was associated with ORs (95% CI) of 1.47 (1.10–1.97) and 1.37 (1.10–1.69), respectively, for gout. In women, hypothyroid status was not associated with hyperuricaemia or gout. However, hyperthyroid status was associated with ORs (95% CI) of 1.42 (1.24–1.62) for hyperuricaemia and 2.13 (1.58–2.87) for gout.ConclusionsBoth hyperthyroid and hypothyroid status were significantly associated with gout and weakly associated with hyperuricaemia. A thyroid function test for gout patients may by warranted.

FRI0382 Gout and hyperuricaemia in people with thyroid dysfunctions

Backgroundfew data are available on the association between thyroid dysfunction and gout and the available evidence were limited by small case number and insufficient confounder control. Earlier studies found high...

Genetic and Environmental Risk Factors in Hyperuricaemia and Common Gout

Gout results from hyperuricaemia. The most important cause of hyperuricaemia is reduced excretion of uric acid in the urine. Genome-wide association scans for genes regulating serum urate concentrations have identified two major regulators – the renal urate transporters SLC2A9 and ABCG2. The risk variants at each gene approximately double the risk for gout in people of Caucasian ancestry, with the urate and fructose transporter SLC2A9 also resulting in higher risk for gout in people of Polynesian ancestry, a diverse population characterized by a high prevalence of gout. Ongoing genetic association studies are identifying and confirming other genes (URAT1, OAT4, NPT1, PDZK1, GCKR) controlling serum urate concentrations; although genome-wide association studies in gout per se await recruitment of suitable case sample sets. The recent increase in gout incidence can only be explained by a change in the environment. One factor that fulfills most of the requirements for confirmation of an etiological role in gout is fructose. Fructose raises serum urate levels, which is exacerbated in people with genetic variants that reduce renal urate excretion, thus increasing the risk of gout. Use of GWAS approaches and application of new genomics technologies such as next-generation sequencing to very large well-phenotyped gout sample sets will enable identification of further genetic risk factors in gout. Intervention studies in cohorts characterized for genetic risk factors are needed to prove a direct link for environmental agents such as fructose in gout etiology. Keywords: Gout, gene, urate transporter, association, genome, SLC2A9, monosodium urate, Caucasian, Hyperuricaemia, polymorphisms, glucokinase

Bases génétiques de l’hyperuricémie et de la goutte

Gout results from elevated urate concentrations in the blood (hyperuricaemia). When super-saturation of urate is reached, monosodium urate crystals form within the joint. In some individuals, these crystals elicit a painful self-limiting inflammatory response that is characteristic of acute gouty arthritis. The most important cause of hyperuricaemia is reduced excretion of uric acid in the urine. Uric acid excretion is coordinated by a suite of urate transport molecules expressed in the renal collecting tubules, and is a key physiological checkpoint in gout. Other checkpoints in gout are hepatic production of urate, monosodium urate crystal formation, and initiation of the acute inflammatory response. Genome-wide association scans for genes regulating serum urate concentrations have identified two major regulators of hyperuricaemia– the renal urate transporters SLC2A9 and ABCG2. The risk variants at each gene approximately double the risk for gout in people of Caucasian ancestry, with SLC2A9 also resulting in higher risk for gout in people of Polynesian ancestry, a diverse population characterized by a high prevalence of gout. Ongoing genetic association studies are identifying and confirming other genes controlling serum urate concentrations; although genome-wide association studies in gout per se await recruitment of suitable case sample sets.

The genetic basis of hyperuricaemia and gout

Gout results from elevated urate concentrations in the blood (hyperuricaemia). When super-saturation of urate is reached, monosodium urate crystals form within the joint. In some individuals, these crystals elicit a painful self-limiting inflammatory response that is characteristic of acute gouty arthritis. The most important cause of hyperuricaemia is reduced excretion of uric acid in the urine. Uric acid excretion is coordinated by a suite of urate transport molecules expressed in the renal collecting tubules, and is a key physiological checkpoint in gout. Other checkpoints in gout are hepatic production of urate, monosodium urate crystal formation, and initiation of the acute inflammatory response. Genome-wide association scans for genes regulating serum urate concentrations have identified two major regulators of hyperuricaemia– the renal urate transporters SLC2A9 and ABCG2. The risk variants at each gene approximately double the risk for gout in people of Caucasian ancestry, with SLC2A9 also resulting in higher risk for gout in people of Polynesian ancestry, a diverse population characterized by a high prevalence of gout. Ongoing genetic association studies are identifying and confirming other genes controlling serum urate concentrations; although genome-wide association studies in gout per se await recruitment of suitable case sample sets.

20 CLINICAL ASPECTS OF GOUTY PATIENTS IN TAIWAN

Before World War II, the incidence of gout had been low in Taiwan and has begun to increase only after the war, probably reflecting the change of the diet due to the economical development and improved standards of living in the country. Since our clinic was established in 1983, we have seen a total number of approximately 4,000 patients with gout. The diagnosis of gout was made according to the criteria proposed by the American Rheumatism Association. For every gouty patient visiting our clinic for the first time, the serum urate concentration and the amount of urate in the 24-hour urine were examined. The serum urate concentration was checked at 2 months intervals in order to monitor the effects of drugs. In addition to these tests, general data including hematological findings, serum biochemistry information, urine analysis, renal function, chest X-ray examincation and EKG were obtained every one year for each patient. The data from these 4,000 patients have been accumulated and submitted to the analysis by a computer. Based on such clinical and laboratory observations and the results obtained by the analysis, we discuss about characteristic features of gout in people in Taiwan.

Identification of urate crystals in gouty synovial fluid.

Excerpt Urate crystals have been noted in synovial fluid from gouty patients in the past, but this finding was believed to be infrequent and of little assistance to the clinician in his attempt to ...