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Gout, urate-lowering therapy, and uric acid levels among adults in the United States.

ABSTRACT: Evidence strongly suggests that delivery of gout care is suboptimal. The 2012 American College of Rheumatology (ACR) guidelines emphasize a serum uric acid (SUA) target of <6 mg/dl when utilizing urate-lowering therapy (ULT). However, the proportion and characteristics of Americans with gout receiving ULT, or with a ULT indication, who are achieving this target is unknown.We identified US adults with gout receiving ULT, and those with an indication for ULT, using the National Health and Nutrition Examination Surveys from 2007-2010. Using the ACR guidelines, a ULT indication comprised chronic kidney disease (CKD) stage 2-5, a history of nephrolithiasis, or current ULT use. Demographic and clinical factors associated with an SUA ?6 mg/dl were determined using Poisson regression.In 2007-2010, an estimated 4.5 million US adults with gout had an indication for ULT; two-thirds had an SUA ?6 mg/dl. In adjusted analyses among those with gout and CKD or nephrolithiasis, those age ?70 years were less likely (prevalence ratio [PR] 0.77, 95% confidence interval [95% CI] 0.61-0.97) to have an SUA ?6 mg/dl. Regarding those taking ULT, hypertension was related to a reduced prevalence (PR 0.51, 95% CI 0.30-0.87), whereas diabetes mellitus (PR 1.42, 95% CI 1.06-1.90) and obesity (PR 1.74, 95% CI 1.19-2.56) were each associated with a higher prevalence of an SUA value ?6 mg/dl.Half of all Americans with gout receiving ULT, and two-thirds with an indication for ULT, have an SUA above target. This study furnishes a meaningful baseline for assessing the effectiveness of the ACR guidelines in future years.

SUBMITTER: Juraschek SP

PROVIDER: S-EPMC4362996 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Gout, urate-lowering therapy, and uric acid levels among adults in the United States.

Juraschek Stephen P SP Kovell Lara C LC Miller Edgar R ER Gelber Allan C AC

Arthritis care & research 20150401 4

<h4>Objective</h4>Evidence strongly suggests that delivery of gout care is suboptimal. The 2012 American College of Rheumatology (ACR) guidelines emphasize a serum uric acid (SUA) target of <6 mg/dl when utilizing urate-lowering therapy (ULT). However, the proportion and characteristics of Americans with gout receiving ULT, or with a ULT indication, who are achieving this target is unknown.<h4>Methods</h4>We identified US adults with gout receiving ULT, and those with an indication for ULT, usin ...[more]

PMID: 25201123

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Project description:BackgroundPrevious studies have noted significant variation in serum urate (sUA) levels, and it is unknown how this influences the accuracy of hyperuricemia classification based on single data points. Despite this known variability, hyperuricemic patients are often used as a control group in gout studies. Our objective was to determine the accuracy of hyperuricemia classifications based on single data points versus multiple data points given the degree of variability observed with serial measurements of sUA.MethodsData was analyzed from a cross-over clinical trial of urate-lowering therapy in young adults without a gout diagnosis. In the control phase, sUA levels used for this analysis were collected at 2-4 week intervals. Mean coefficient of variation for sUA was determined, as were rates of conversion between normouricemia (sUA ≤6.8 mg/dL) and hyperuricemia (sUA > 6.8 mg/dL).ResultsMean study participant (n = 85) age was 27.8 ± 7.0 years, with 39% female participants and 41% African-American participants. Mean sUA coefficient of variation was 8.5% ± 4.9% (1 to 23%). There was no significant difference in variation between men and women, or between participants initially normouricemic and those who were initially hyperuricemic. Among those initially normouricemic (n = 72), 21% converted to hyperuricemia during at least one subsequent measurement. The subgroup with initial sUA < 6.0 (n = 54) was much less likely to have future values in the range of hyperuricemia compared to the group with screening sUA values between 6.0-6.8 (n = 18) (7% vs 39%, p = 0.0037). Of the participants initially hyperuricemic (n = 13), 46% were later normouricemic during at least one measurement.ConclusionSingle sUA measurements were unreliable in hyperuricemia classification due to spontaneous variation. Knowing this, if a single measurement must be used in classification, it is worth noting that those with an sUA of < 6.0 mg/dL were less likely to demonstrate future hyperuricemic measurements and this could be considered a safer threshold to rule out intermittent hyperuricemia based on a single measurement point.Trial registrationData from parent study ClinicalTrials.gov Identifier: NCT02038179 .

Project description:Andrographis paniculata (Burm.f.) Nees has been found to have anti-inflammatory and immunostimulatory effects. This study was to investigate antihyperuricemic and anti-inflammatory effects of A. paniculata leaf extracts. Andrographolide, 14-deoxy-11,12-didehydroandrographolide, and neoandrographolide were quantified in 80% ethanol (EtOH80) and water extracts using High Performance Liquid Chromatography (HPLC) analysis. Antihyperuricemic activity was evaluated using a spectrophotometric in vitro inhibitory xanthine oxidase (XO) assay. The most active extract and andrographolide were further investigated in a hyperuricemic rat model induced by potassium oxonate to determine serum uric acid levels, liver XO activity, followed by Western blot analysis for renal urate transporter URAT1, GLUT9, and OAT1 to investigate the excretion of uric acid via kidney. Anti-inflammatory activity was assessed by in vitro interleukin assay for interleukin (IL-1α, IL-1β, IL-6, IL-8), and tumor necrosis factor (TNF-α) in monosodium urate (MSU) crystal-induced human fibroblast-like synoviocyte (HFLS) cells using ELISA-kits, followed by Western blot analysis for the expression of MyD88, NLRP3, NF-κB p65, and caspase-1 proteins to investigate the inflammation pathway. In vivo assay of the most active extract and andrographolide were performed based on the swelling rate and inhibition of pro-inflammatory mediator release from synovial fluid of a rat knee joint induced by MSU crystals. The results showed that the EtOH80 extract had a greater amount of andrographolide (11.34% w/w) than the water extract (1.38% w/w). In the XO inhibitory activity, none of the samples exhibited greater than 50% inhibition. However, in a rat model, EtOH80 extract (200 mg/kg/day) and andrographolide (30 mg/kg/day) decreased serum uric acid levels and reduced liver XO activity, reduced the protein expression levels of URAT1 and GLUT9, and restored the decrease in OAT1 levels. In the in vitro anti-inflammatory study, EtOH80 extract and andrographolide significantly decreased production of IL-1α, IL-1β, IL-6, and TNF-α, as well as inhibited the synthesis of MyD88, NLRP3, NF-κB p65, and caspase-1 in a concentration-dependent manner, almost comparable to dexamethasone. The EtOH80 extract (200 mg/kg/day) and andrographolide (30 mg/kg) significantly decreased swelling rate and IL-1α, IL-1β, IL-6, and TNF-α in the synovial fluid of rat models in a time-dependent manner, comparable to indomethacin (3 mg/kg/day). In conclusion, the findings show that EtOH80 extract has a substantial anti-gout effect by lowering uric acid levels and suppressing pro-inflammatory mediator production due to the andrographolide content, that might be beneficial in the treatment of gouty-inflammation.

Project description:BackgroundGout has an increasing global prevalence. Underutilization of urate-lowering therapy (ULT) is thought to be common, via both suboptimal dosing and poor medication adherence. The aims of this study were to determine the prevalence of self-reported gout and the key predictors of ULT use in those with gout in a representative population survey in South Australia.MethodsData were obtained from the Spring 2015 South Australian Health Omnibus Survey, a multilevel, systematic, survey in a representative population sample involving face-to-face interviews (n = 3005). This study analyzed responses from respondents aged ≥ 25 years (n = 2531) about self-reported gout, ULT use, sociodemographic factors, lifestyle factors, and comorbidities, using survey weighting. Univariate and subsequent adjusted logistic regression analyses on self-reported gout were performed. ULT use was divided into three categories (never use, prior use, and current use) and these data were analyzed using a multinomial logistic regression model.ResultsSelf-reported gout prevalence was 6.8% (95% CI 5.8, 7.9). The mean age of respondents with gout was 64 years (standard deviation 16) and 82% were male. As expected, older age, male gender, lower socioeconomic status (SES), and higher body mass index (BMI) were associated with gout, as were high alcohol consumption, current smoking, other forms of arthritis, and hypertension or hypercholesterolemia medication, after adjustment for sociodemographic variables. Two thirds of respondents with gout reported ULT use (36% current; 29% previous) with only 55% continuing treatment. Predictors of ULT use included male gender, low SES, and concomitant cholesterol-lowering therapy. Respondents with gout with a higher BMI were more likely to remain on ULT.ConclusionsDespite gout being a common, potentially disabling joint disease, only 55% of respondents with gout in this study adhered to ULT. Identification of key predictors of ULT use will provide guidance on prescribing strategy in clinical practice and on the quality of gout care in the community.

Dataset Information

Gout, urate-lowering therapy, and uric acid levels among adults in the United States.

Publications

Gout, urate-lowering therapy, and uric acid levels among adults in the United States.

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