The renal mechanism for urate homeostasis in normal man

Steele, Thomas H.; Rieselbach, Richard E.

doi:10.1016/0002-9343(67)90245-8

Cited by 188 publications

(113 citation statements)

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“…Pyrazinoic acid is the active metabolite of pyrazinamide that inhibits the renal tubular secretion of uric acid (12,25). We utilized pyrazinoic acid to dissect out the contribution of secreted uric acid to urinary excretion of uric acid.…”

Section: Discussionmentioning

confidence: 99%

“…The rat is a useful animal for evaluating drug effects on uric acid excretion because the net flux in the tubular excretory transport of uric acid is reabsorptive, although the fractional excretion of uric acid is obviously higher than that in man (9)(10)(11)(12)(13). Thus, we utilized rats as the animal for evaluating the action of diuretics on the uric acid transport system.…”

mentioning

confidence: 99%

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Decreased renal excretion of uric acid following diuretic administration in rats.

Iwaki

Yonetani

1984

Jpn.J.Pharmacol

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Decreased renal excretion of uric acid following diuretic administration in rats.

Iwaki

Yonetani

1984

Jpn.J.Pharmacol

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“…Thus in the presence of secretory inhibition by pyrazinamide even greatly elevated filtered urate loads can be almost completely reabsorbed. This fact stands in marked contrast to the baseline situation (ie without pyrazinamide) in which RNA loading is known to augment greatly urate excretion (41). These results suggest that filtered urate can be reabsorbed far more extensively than secreted urate.…”

Section: Thomas H Steelementioning

confidence: 59%

“…Formerly it was thought that filtered urate was extensively reabsorbed, following which most of the urate destined to find its way into the final urine was added by tubular secretion ( Figure 8A). T h e finding that approximately 80y0 of the urate excretion was suppressible by pyrazinamide and that the nonsuppressible urate excretion approximated only 2y0 of the filtered urate load suggested that the control of urate excretion lay almost totally within the secretory system (41). Subsequently, with the appearance of evidence suggesting the existence of a postsecretory component of urate reabsorption and high bidirectional fluxes for intrarenal urate transport, questions regarding the magnitude of presecretory reabsorption have arisen.…”

Section: Thomas H Steelementioning

confidence: 99%

Renal excretion of uric acid

Steele

1975

Arthritis & Rheumatism

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I n earlier years of renal physiology study, the developnient of the inulin clearance for the estimation of the glomerular filtration rate (GFR) allowed a precise comparison between the excretion and filtration rates of many urinary solutes. Although it soon was realized that many members of a large group of weak organic acids are avidly bound by the kidney and undergo net tubular secretion, studies in several species including man indicated that the rate of uric acid excretion was far less than its rate of filtration. Even though the possibility was raised that polymerized or protein-bound aggregates of urate not amenable to glomerular filtration might exist in plasma (l), the prevailing opinion was that urate simply underwent complete glomerular filtration and partial tubular reabsorption. Extensive studies were reported in 1950 by Berliner et al (Z), in which urate titration procedures were performed in an attempt further to characterize urate reabsorption within the normal kidney. During the progressive infusion of urate, the difference between the rates of filtration and excretion of urate increased progressively. Berliner and his coworkers ultimately concluded that a maximum urate reabsorption rate probably exists in normal man, but that the ap- parent capacity for urate reabsorption is so great that it would not become fully saturated under normal conditions (2). Although Praetorius and Kirk (3) described a hypouricemic patient who demonstrated net urate secretion in 1950, the possible existence of a significant amount of tubular secretion of urate in man was not widely accepted. Subsequently, renewed interest in renal urate secretion occurred, largely as a result of work from the laboratory of the late Dr. Alexander Gutman. Gutman and Y u raised the question of the existence of urate secretion in man based on observations during clearance studies in gouty patients and normal persons (4). Even in their early reports, they hypothesized that large transtubular fluxes of urate might exist, for if secretion of urate did occur then the calculated net reabsorptive rates of urate would be too low. Subsequent observations elucidating the remarkable "paradoxical actions" of certain pharmacologic agents on urate excretion (5) and also the antiuricosuric effect of pyrazinamide (PZA) administration (6) raised the possibility that inhibition of the tubular secretion of urate could substantially reduce urate excretion. Although Gutman and his colleagues acknowledged that an enhanced rate of urate reabsorption could also have produced an antiuricosuric effect, they visualized that if virtually complete reabsorption of the filtered urate occurred within the nephron and if the urinary uric acid were derived primarily from

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“…This decrease could be the result of an alteration in glomerular filtration, renal tubular reabsorption, or renal tubular secretion of uric acid. Because of the virtual disappearance of uric acid from the urine of subjects taking maximal doses of pyrazinamide, it was proposed that PZA produced this effect through the single action of completely inhibiting uric acid secretion (2). T h e proposal led to the introduction of the "pyrazinamide suppression test," which has been used extensively in clinical studies in an attempt to differentiate changes in uric acid secretion from changes in uric acid reabsorption.…”

mentioning

confidence: 99%