Reassessing serum urate targets in the management of refractory gout: can you go too low?
OBJECTIVE
Growing awareness of patients with refractory gout is prompting a reassessment of treatment strategy. This article reviews the current practice of targeting serum urate concentrations (sUA) in the mid-normal range (roughly 4-6 mg/dl) and considers the rationale for more aggressively lowering sUA in patients with poorly controlled chronic gout. Some hypothetical concerns with inducing hypouricemia are considered and relevant clinical evidence is evaluated.


RESULTS
Recent studies confirm the benefits of modestly reducing sUA in many gout patients. However, tophi and tissue stores of monosodium urate crystals resolve slowly, particularly in patients with longstanding disease. Consistent with physicochemical principles, the rate of decrease in tophus size increases with a reduction in sUA concentration over a broad range. Reducing sUA to near or below 2 mg/dl can be achieved in some patients with current urate-lowering drugs, but new drugs now under investigation may be more effective. As a free radical scavenger, uric acid has been postulated to protect from oxidative stress. However, inherited disorders associated with profound, lifelong hypouricemia indicate that maintaining sUA near or below 2 mg/dl would probably be safe.


CONCLUSIONS
Targeting low sUA could improve the elimination of tissue urate stores and achieve better control of disease in patients with refractory gout.
Hershfield
Michael S
MS
Duke University Medical Center, Durham, North Carolina 27710, USA. msh@biochem.duke.edu