Pathogenesis of gout

被引:720
作者
Choi, HK [1 ]
Mount, DB [1 ]
Reginato, AM [1 ]
机构
[1] Univ British Columbia, Dept Med, Div Rheumatol, Arthrit Res Ctr, Vancouver, BC V5Z 1L7, Canada
关键词
D O I
10.7326/0003-4819-143-7-200510040-00009
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. © 2005 American College of Physicians.
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页码:499 / 516
页数:18
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