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Pathogenesis of Gout
- Hyon K. Choi, MD, DrPH;
- David B. Mount, MD; and
- Anthony M. Reginato, MD, PhD
- From Arthritis Research Centre of Canada, University of British Columbia, Vancouver, British Columbia, Canada; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, and VA Boston Healthcare System, Boston, Massachusetts.
PHYSIOLOGY IN MEDICINE: A SERIES OF ARTICLES LINKING MEDICINE WITH SCIENCE
Co-sponsored by the American College of Physicians and the American Physiological Society
Physiology in Medicine: Dennis A. Ausiello, MD, Editor; Dale J. Benos, PhD, Deputy Editor; Francois Abboud, MD, Associate Editor; William J. Koopman, MD, Associate Editor
Annals of Internal Medicine: Paul Epstein, MD, Series Editor
Clinical Principles
The overall disease burden of gout is substantial and may be increasing.
As more scientific data on the modifiable risk factors and comorbidities of gout become available, integration of these data into gout care strategies may become essential.
Hyperuricemia and gout are associated with the insulin resistance syndrome and related comorbid conditions.
Lifestyle modifications that are recommended for gout generally align with those for major chronic disorders (such as the insulin resistance syndrome, hypertension, and cardiovascular disorders); thus, these measures may be doubly beneficial for many patients with gout and particularly for individuals with these comorbid conditions.
Effective management of risk factors for gout and careful selection of certain therapies for comorbid conditions (such as hypertension or the insulin resistance syndrome) may also aid gout care.
The urate–anion exchanger URAT1 (urate transporter-1) is a specific target of action for both antiuricosuric and uricosuric agents.
The long-term health effect of hyperuricemia (beyond the increased risk for gout) needs to be clarified, including any potential consequences associated with the chronic hyperuricemia that anti-inflammatory treatment does not correct.
Pathophysiologic Principles
A direct causal relationship exists between serum urate levels and the risk for gout.
Lifestyle factors, including adiposity and dietary habits, appear to contribute to serum uric acid levels and the risk for gout.
Urate is extensively reabsorbed from the glomerular ultrafiltrate in the proximal tubule via the brush-border urate–anion exchanger URAT1.
Sodium-dependent reabsorption of anions increases their concentration in proximal tubule cells, resulting in increased urate …
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