Pathogenesis of Gout

Arthritis Research Centre of Canada, University of British Columbia, Vancouver, British Columbia, Canada.
Annals of internal medicine (Impact Factor: 17.81). 11/2005; 143(7):499-516. DOI: 10.7326/0003-4819-143-7-200510040-00009
Source: PubMed


The disease burden of gout remains substantial and may be increasing. As more scientific data on modifiable risk factors and comorbidities of gout become available, integration of these data into gout care strategy may become essential, similar to the current care strategies for hypertension (163) and type 2 diabetes (164). Recommendations for lifestyle modification to treat or to prevent gout are generally in line with those for the prevention or treatment of other major chronic disorders (32). Thus, the net health benefits from these general healthy lifestyle recommendations (32) are expected to be even larger among many patients with gout, particularly those with coexisting insulin resistance syndrome, diabetes, obesity, and hypertension. Weight control, limits on red meat consumption, and daily exercise are important foundations of lifestyle modification recommendations for patients with gout or hyperuricemia and parallel recommendations related to prevention of coronary heart disease, diabetes, and certain types of cancer. Patients with gout could consider using plant-derived ω-3 fatty acids or supplements of eicosapentaenoic acid and docosahexarioic acid instead of consuming fish for cardiovascular benefits. The recent recommendation on dairy consumption for the general public would also be applicable for most patients with gout or hyperuricemia and may offer added benefit to individuals with hypertension, diabetes, and cardiovascular disorders. Further risk-benefit assessments in each specific clinical context would be helpful. Daily consumption of nuts and legumes as recommended by the Harvard Healthy Eating Pyramid (32) may also provide important health benefits without increasing the risk for gout. Similarly, a daily glass of wine may benefit health without imposing an elevated risk for gout, especially in contrast to beer or liquor consumption. These lifestyle modifications are inexpensive and safe and, when combined with drug therapy, may result in better control of gout. Effective management of gout risk factors (for example, hypertension) and the strategic choice of certain therapies for comorbid conditions may also aid gout care. For example, antihypertensive agents with uricosuric properties (for example, losartan [165] or amlodipine [86]) could have a better risk-benefit ratio than diuretics for hypertension in hypertensive patients with gout. Similarly, the uricosuric property of fenofibrate (165) may be associated with a favorable risk-benefit ratio among patients with gout and the metabolic syndrome. The recently elucidated molecular mechanism of renal urate transport has several important implications in conditions that are associated with high urate levels. In particular, the molecular characterization of the URAT1 anion exchanger has provided a specific target of action for well-known substances affecting urate levels. Genetic variation in these renal transporters or upstream regulatory factors may explain the genetic tendency to develop conditions associated with high urate levels and a patient's particular response to medications. Furthermore, the transporters themselves may serve as targets for future drug development. Finally, advances in our understanding of crystal-induced inflammation indicate that gout shares many pathogenetic features with other chronic inflammatory disorders. Some newly available potent anti-inflammatory medications (including biological agents that are indicated for other conditions) may have therapeutic potential in selected subsets of patients with gout, although the high costs of biological agents would probably prevent their widespread use in gout. Anti-inflammatory agents for gout (including colchicine) are typically used to treat acute gout or to reduce the risk for rebound gout attacks during the initiation of urate-lowering therapy but do not lower serum levels of uric acid. The long-term safety profile of these agents needs to be clarified, including the potential consequences of chronic hyperuricemia with such anti-inflammatory treatment.

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Available from: Anthony M Reginato
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    • "Hyperuricemia is considered to be a precursor of gout as the deposition of urate crystals in the joints results in an acute inflammatory response. Deposition in the soft tissue can lead to tophi [13] [14] [15]. Gout is also a serious health issue and is an independent risk factor for heart failure and metabolic syndrome [16] [17]. "
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    ABSTRACT: We systematically identified the prevalence of hyperuricemia and gout in mainland China and provided informative data that can be used to create appropriate local public health policies. Relevant articles from 2000 to 2014 were identified by searching 5 electronic databases: PubMed, Google Scholar, Chinese Wanfang, CNKI, and Chongqing VIP. All of the calculations were performed using the Stata 11.0 and SPSS 20.0 software. The eligible articles ( n = 36 ; 3 in English and 33 in Chinese) included 44 studies (38 regarding hyperuricemia and 6 regarding gout). The pooled prevalence of hyperuricemia and gout was 13.3% (95% CI: 11.9%, 14.6%) and 1.1% (95% CI: 0.7%, 1.5%), respectively. Although publication bias was observed, the results did not change after a trim and fill test, indicating that that impact of this bias was likely insignificant. The prevalence of hyperuricemia and gout was high in mainland China. The subgroup analysis suggested that the geographical region, whether the residents dwell in urban or rural and coastal or inland areas, the economic level, and sex may be associated with prevalence.
    Full-text · Article · Nov 2015
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    • "Gout is a common form of inflammatory arthritis in adults and is caused by the deposition of monosodium urate (MSU) crystals in articular and peri-articular structures (Choi et al., 2005). Gout typically presents as episodes of acute inflammatory arthritis interspersed with intercritical asymptomatic periods (Martinon, 2006). "
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    ABSTRACT: Background: Foot and ankle structures are the most commonly affected in people with gout. However, the effect of gout on foot and ankle muscle strength is not well understood. The primary aim of this study was to determine whether differences exist in foot and ankle muscle strength for plantarflexion, dorsiflexion, inversion and eversion between people with gout and age- and sex-matched controls. The secondary aim was to determine whether foot and ankle muscle strength was correlated with foot pain and disability. Methods: Peak isokinetic concentric muscle torque was measured for ankle plantarflexion, dorsiflexion, eversion and inversion in 20 participants with gout and 20 matched controls at two testing velocities (30°/s and 120°/s) using a Biodex dynamometer. Foot pain and disability was measured using the Manchester Foot Pain and Disability Index (MFPDI). Findings: Participants with gout demonstrated reduced muscle strength at both the 30°/s and 120°/s testing velocities for plantarflexion, inversion and eversion (P<0.05). People with gout also displayed a reduced plantarflexion-to-dorsiflexion strength ratio at both 30°/s and 120°/s (P<0.05). Foot pain and disability was higher in people with gout (P<0.0001) and MFPDI scores were inversely correlated with plantarflexion and inversion muscle strength at the 30°/s testing velocity, and plantarflexion, inversion and eversion muscle strength at the 120°/s testing velocity (all P<0.05). Interpretation: People with gout have reduced foot and ankle muscle strength and experience greater foot pain and disability compared to controls. Foot and ankle strength reductions are strongly associated with increased foot pain and disability in people with gout.
    Full-text · Article · Nov 2015 · Clinical biomechanics (Bristol, Avon)
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    • "Their concentrations may affect human health and act as biomarkers for various diseases (Ascherio et al., 2009; Burtis & Ashwood, 2001; Choi, Mount, & Reginato, 2005; Chonchol et al., 2007; Dehghan, van Hoek, Sijbrands, Hofman, & Witteman, 2008; Gagliardi, Miname, & Santos, 2009; Harper, 1977; Heinig & Johnson, 2006; Kassirer, 1971; Krishnan, Kwoh, Schumarcher, & Kuller, 2007; Lapsia et al., 2012; Lin et al., 2011; Mouton & Holder, 2006). The abnormal high concentrations of uric acid in human plasma and urine are associated with several diseases, such as gouty arthritis, hyperuricemia, hypertension, pneumonia, type 2 diabetes, cardiovascular disease and kidney damage (Ascherio et al., 2009; Burtis & Ashwood, 2001; Choi et al., 2005; Chonchol et al., 2007; Dehghan et al., 2008; Gagliardi et al., 2009; Harper, 1977; Heinig & Johnson, 2006; Kassirer, 1971; Krishnan et al., 2007; Lapsia et al., 2012; Lin et al., 2011; Mouton & Holder, 2006). Creatinine, quantitatively excreted in the urine, is nonenzymatically formed from intracellular creatine and phosphocreatine in muscles. "
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    ABSTRACT: Creatinine (Cr), uric (UA) and ascorbic acid (AA) are common constituents in human fluids. Their abnormal concentrations in human fluids are associated with various diseases. Thus, apart from the endogenous formation in human body, it is also important to examine their sources from food products. In this study, a rapid and accurate HILIC method was developed for simultaneous determination of Cr, UA and AA in bovine milk and orange juice. Milk samples were pretreated by protein precipitation, centrifugation and filtration, followed by HPLC separation and quantification using a Waters Spherisorb S5NH2 column. The developed method has been successfully applied to determine the concentration of UA, AA and Cr in milk and fruit juice samples. The milk samples tested were found to contain UA and creatinine in the concentration range of 24.1-86.0 and 5.07-11.2μgmL(-1), respectively. The orange juices contain AA over 212μgmL(-1). Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Sep 2015 · Food Chemistry
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