Gout is known to be undertreated, especially in primary care. The target for serum urate is <6 mg/dL at a minimum, and often <5 mg/dL. Many physicians, however, don’t titrate upward from the starting dose of a first-line pharmacologic therapy with a xanthine oxidase inhibitor (XOI) therapy. The maintenance dose of allopurinol can exceed 300 mg daily, even in patients with chronic kidney disease. If the target is not reached with appropriately dosed XOI monotherapy, adding uricosuric therapy onto an XOI inhibitor is recommended by the ACR 2012 guidelines as the potential next step, depending on appropriateness for the patient.
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Ongoing research has suggested that uric acid and xanthine oxidase in abdominal fat are mediating inflammation and obesity, contributing to the metabolic syndrome (see figure, left). Xanthine oxidase acts partly on adipose tissue by regulating PPARgamma and adipogenesis. All of these associations highlight the importance of comprehensive management of gout and associated comorbidities, including obesity, Dr. Terkeltaub says.
Kathy L. Holliman, MEd, is a medical writer based in Beverly, Mass.
> ↑ Body mass index (BMI), associated with hyperuricemia & increased incident gout risk (>3-fold OR: BMI 30–34.9)3
> Mechanisms by which obesity promotes both hyperuricemia and gout:
— ••Insulin resistance decreased renal uric acid excretion systemic inflammatory state
— ••? ↑ Leptin (decreased renal uric acid excretion)4
— ••↑ Adipocyte xanthine oxidase (XO) and urate generation, secretion5
— ••Too much or too little XO–> fat tissue inflammation5,6
— ••XO–>PPARg –> adipogenesis5,6
— ••(?) Soluble uric acid in fat –> promotes fat tissue inflammation, obesity, metabolic syndrome7
Table source: Chart created by Robert Terkeltaub, MD, and used with permission.
- Dalbeth N, Chen P, White M, et al. Impact of bariatric surgery on serum urate targets in people with morbid obesity and diabetes: A prospective longitudinal study. Ann Rheum Dis. 2014;73:797–802.
- Khanna D, FitzGerald JD, Khanna PP, et al. 2012 American College of Rheumatology Guidelines for Management of Gout. Part I: Systematic Nonpharmacologic and Pharmacologic Therapeutic Approaches to Hyperuricemia. Arthritis Care Res (Hoboken). 2012;64:1447–1461.
- Choi HK, Ford ES, Li C, et al. Prevalence of the metabolic syndrome in patients with gout: The Third National Health and Nutrition Examination Survey. Arthritis Rheum. 2007 Feb 15;57(1):109–115.
- de Oliveira EP, Burini RC. High plasma uric acid concentration: Causes and consequences. Diabetol Metab Syndr. 2012 Apr 4;4:12.
- Tsushima Y, Nishizawa H, Tochino Y, et al. Uric acid secretion from adipose tissue and its increase in obesity. J Biol Chem. 2013 Sep. 20;288(38):27138–27349.
- Murakami N, Ohtsubo T, Kansui Y, et al. Mice heterozygous for the xanthine oxidoreductase gene facilitate lipid accumulation in adipocytes. Arterioscler Thromb Vasc Biol. 2014 Jan;34(1):44–51.
- Baldwin W, McRae S, Marek G, et al. Hyperuricemia as a mediator of the proinflammatory endocrine imbalance in the adipose tissue in a murine model of the metabolic syndrome. Diabetes. 2011 Apr;60(4):1258–1269.