Localization and Pyrazinamide Inhibition of Distal Trans- tubular Movement of Uric Acid-2-C"4 with a Modi- fied Stop-Flow Technique *

Renal tubular secretion of uric acid has been demonstrated in several mammalian species in-cluding 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 neces-sary 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 infu-sion of urate (1). In 1959, Gutman, Yfi, and Berger (7) documented tubular secretion of uric acid in patients with reduced glomerular filtra-tion, who were given infusions of uric acid and mannitol and treated with large doses of sulfinpy-razone in order to suppress tubular reabsorption. One year later tubular secretion of urate was reported in the mongrel dog under similar condi-tions of an osmotic diuresis and an intravenous infusion of uric acid (2, 3). Efforts to localize the site of tubular urate se-cretion in the mongrel dog by stop-flow analysis have yielded conflicting results. Yu and his col-leagues (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 ad-ministration of probenecid, found no evidence for distal tubular secretion of urate. *Submitted for publication October 19, 1964; accepte