Synthesis of uric acid in isolated normothermic perfused mongrel and Dalmatian dog kidneys.

Renal synthesis of uric acid (urate) in the dog was demonstrated by use of two isolated kidney preparations during pulsatile perfusion at 37 degrees C with artificial perfusate or with a plasma fraction. During perfusion of mongrel and Dalmatian dog kidneys with 0.5 mg of [14C]xanthine per 100 ml, a mean of 24.3 and 25.4 mug of [14C]urate per minute, respectively, entered either urine or perfusate after its synthesis in the isolated kidney. Approximately 6.2% of the combined extracellular radiolabeled urate formed in the isolated mongrel kidney was excreted in the urine and 15.7% in the urine of isolated Dalmatian dog kidneys. Recirculating the perfusate without the kidney did not convert any radioactively labeled xanthine to urate and therefore the radioactively labeled urate appearing in the urine and recycled perfusate must have been formed in the renal parenchyma. Renal synthesis of urate was blocked by the xanthine oxidase inhibitor allopurinol. In the presence of allopurinol, [14C]xanthine was excreted unchanged into the urine.