Localization and Pyrazinamide Inhibition of Distal Transtubular Movement of Uric Acid-2-c14 with a Modified Stop-flow Technique.

Renal tubular secretion of uric acid has been demonstrated in several mammalian species including the rabbit (1), mongrel and Dalmatian dog (24), and man (7). Although secretion was easily delineated in the Dalmatian coach hound (4-6), special experimental conditions were necessary for its substantiation in other species. Uric acid clearance in excess of simultaneous creatinine clearance, indicative of tubular secretion of urate, was noted by Poulsen and Praetorius in rabbits made hyperuricemic by the intravenous infusion of urate (1). In 1959, Gutman, Yfi, and Berger (7) documented tubular secretion of uric acid in patients with reduced glomerular filtration, who were given infusions of uric acid and mannitol and treated with large doses of sulfinpyrazone in order to suppress tubular reabsorption. One year later tubular secretion of urate was reported in the mongrel dog under similar conditions of an osmotic diuresis and an intravenous infusion of uric acid (2, 3). Efforts to localize the site of tubular urate secretion in the mongrel dog by stop-flow analysis have yielded conflicting results. Yu and his colleagues (3, 8) reported peak net tubular secretion in the distal segment of the nephron. However, Kessler, Hierholzer, and Gurd (6), utilizing the same experimental procedure except for the administration of probenecid, found no evidence for distal tubular secretion of urate.