A two-stage approach to the treatment of hyperuricemia in gout: The Dirty Dish hypothesis

Objective It is commonly accepted that the target serum urate level in patients receiving urate-lowering therapy for dissolution of urate crystals in hyperuricemia of gout is <6 mg/dl, and that patients with gout should continue urate-lowering therapy for the rest of their lives. This study was undertaken to reevaluate whether this stringent therapeutic target to dissolve crystals must be maintained lifelong to prevent new crystal formation. Methods. In a prospective cohort of 211 patients with gout, urate-lowering therapy was withdrawn after 5 years if no tophus was present at baseline, or 5 years after resolution of the last tophus. Data on recurrence of gout and on serum urate levels and other potentially associated variables were analyzed. Results. Multivariate regression analysis of time to crystal-proven recurrence of gout showed that serum urate levels during urate-lowering treatment and after its withdrawal were independently related to gout recurrence. None of the patients who had average serum urate levels of <7 mg/dl after urate-lowering therapy withdrawal developed a crystal-proven recurrence of gout. Post hoc analysis showed that weight loss and use of drugs that lower serum urate, such as losartan or fenofibrate, were associated with serum urate levels of < 7 mg/dl during followup after urate-lowering therapy withdrawal; use of diuretics was associated with failure to achieve serum urate levels of < 7 mg/dl during followup. Conclusion. Our data support the hypothesis that after appropriate long-term treatment of hyperuricemia in gout with urate crystal dissolution being the therapeutic target, lifelong treatment can be targeted to achieve serum urate levels just below the threshold for saturation to avoid new crystal formation, similar to cleaning a dirty dish: more is required to get it clean than to keep it clean.