Hyperuricemia and renal insufficiency associated with malignant disease: Urate oxidase as an efficient therapy?

Hyperuricemia is a common finding in patients with malignant diseases. Chem otherapy can induce life-threatening tumor lysis syndrome with severe hyper uricemia, other metabolic abnormalities, and acute renal failure, Intrarena l precipitation of uric acid contributes to renal insufficiency in this sit uation. Allopurinol, by preventing the conversion of hypoxanthine and xanth ine to uric acid, has been long considered the standard pharmacological app roach to hyperuricemia and prevention of tumor lysis syndrome. However, all opurinol itself may facilitate precipitation of xanthine crystals and has l ittle influence on already-formed uric acid crystals deposited in the kidne y. Urate oxidase further oxidizes uric acid to the highly water-soluble all antoin in mammals, except humans, who lack this enzyme, We report four case s of hyperuricemia (initial serum uric acid concentrations, 14.0 to 25.0 mg /dL) associated with malignant diseases treated with exogenous urate oxidas e, Two of the patients showed full-blown tumor lysis syndrome. A single ura te oxidase infusion (1,000 U) readily reduced serum uric acid levels in all patients, Furthermore, renal insufficiency, determined by serum creatinine concentrations, improved in three of the four patients. No adverse effects were observed. Currently, a recombinant urate oxidase is undergoing clinic al testing and may make this efficient therapy more widely available. We be lieve that treatment with urate oxidase is a safe and efficient therapy for patients with cancer-associated hyperuricemia and may be effective even in individuals with only moderately elevated serum uric acid concentrations. (C) 1999 by the National Kidney Foundation, Inc.