uratelowering

Urate-lowering therapy refers to medical interventions designed to reduce the level of uric acid in the blood, with the aim of preventing urate crystal formation in joints and tissues. It is commonly used to manage hyperuricemia and gout, and may be employed in the prevention of uric acid–related complications in conditions such as tumor lysis syndrome. The goal of treatment is to maintain serum urate at a level that minimizes crystal deposition, often below 6 mg/dL (360 µmol/L), with tighter targets sometimes recommended for patients with tophi or frequent flares.

Urate-lowering strategies fall into several categories. Production-lowering agents inhibit uric acid synthesis, most notably xanthine oxidase inhibitors such as allopurinol and febuxostat. Agents that increase uric acid excretion, including uricosurics like probenecid and lesinurad, reduce renal reabsorption of urate. In some situations, enzymes that metabolize uric acid, such as uricase preparations (rasburicase, pegloticase), are used for severe or refractory hyperuricemia, particularly in cancer patients with tumor lysis syndrome or chronic gout with extensive tophi.

Clinical use typically involves long-term management rather than short-term treatment of acute flares. Initiation of urate-lowering therapy can provoke flares, so concomitant anti-inflammatory prophylaxis (e.g., NSAIDs or colchicine) is often employed during dose titration. Safety considerations vary by agent: allopurinol carries a risk of hypersensitivity in certain populations, febuxostat has been associated with cardiovascular concerns in some studies, and pegloticase requires monitoring for infusion reactions and loss of response.

References guidelines from rheumatology societies guide target levels, monitoring intervals, and dose adjustments based on patient risk factors and comorbidities.