Cholangiocarcinoma and Severe Renal Hypouricemia: A Study of the Renal Mechanisms

Hypouricemia in malignant neoplasms is rarely reported. We present a previously unreported case of cholangiocarcinoma associated with severe persistent hypouricemia (serum uric acid levels ranged from 0.07 to 0.08 mmol/L [1.16 to 1.40 mg/100 mL], and increased urate clearance (50.90 to 57.33 mL/min v a mean value in 20 normal subjects of 9.75 ± 1.65 mL/min). High fractional urate clearance (C us /C cr = 0.50 to 0.58 v 0.09 ± 0.01 in normals) was suppressed only slightly following pyrazinamide (PZA), to 0.29 versus 0.007, and was surprisingly enhanced by probenecid (PB) to 1.78 versus 0.63 in normals. No other renal tubular or metabolic abnormalities were detected. This previously unreported association of a high PZA-nonsuppressible urate excretion with a postprobenecid urate clearance exceeding glomerular filtration rate suggests that a combined renal tubular defect is responsible for hypouricemia. The patient described here provides evidence to support the presence of a presecretory reabsorptive defect in association with a "relatively high" urate secretion by the renal tubule. This report adds to the list of hypouricemic conditions and presents an important clue to elucidate urate handling mechanisms in man.