The Renal Excretion of Uric Acid in Patients With Gout and in Nongouty Subjects *†

Nugent, Charles A.; Tyler, Frank H.

doi:10.1172/jci103966

Cited by 128 publications

(45 citation statements)

References 16 publications

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“…Under such circumstances, when plasma urate levels are increased by the oral administration of ribonucleic acid (6) or by the administration of urate intravenously, as was done in the present study, a distinct impairment of urate excretion and clearance is apparent in individuals with gout.…”

Section: Discussionsupporting

confidence: 53%

“…In order to eliminate such differences Nugent and Tyler (6) induced hyperuricemia in nongouty individuals by the oral administration of uric acid precursors and compared uric acid excretion in these subjects and patients with gout. Under these conditions an impairment in urate excretion was clearly evident in patients with gout; both the excretion and clearance of urate were significantly less than in nongouty subjects with equivalent plasma urate levels.…”

Section: Impairment Of Uric Acid Excretion In Goutmentioning

confidence: 99%

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Impairment of Uric Acid Excretion in Gout*

Lathem

Rodnan²

1962

J. Clin. Invest.

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The urinary excretion of uric acid in individuals with primary gout has been shown to be approximately the same as, or in a minority of instances greater than, that of normal subjects on comparable diets (2, 3). These observations, plus the failure to demonstrate significant differences in the renal clearance of uric acid in gouty and nongouty control subjects, have led to the conclusion that patients with gout excrete uric acid in a normal manner (2-5).This view has, however, recently been challenged (6) on the ground that in the studies on which it was based, differences in the plasma urate concentrations of gouty and nongouty subjects were not taken into account. In order to eliminate such differences Nugent and Tyler (6) induced hyperuricemia in nongouty individuals by the oral administration of uric acid precursors and compared uric acid excretion in these subjects and patients with gout. Under these conditions an impairment in urate excretion was clearly evident in patients with gout; both the excretion and clearance of urate were significantly less than in nongouty subjects with equivalent plasma urate levels.These observations of impaired uric acid excretion were fully supported by the present study, in which urate was administered intravenously to gouty and nongouty subjects in order to a) study urate excretion at equivalent and various plasma levels and b) examine the dynamics of the renal tubular transfer mechanisms for urate.

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Section: Discussionsupporting

confidence: 53%

Section: Impairment Of Uric Acid Excretion In Goutmentioning

confidence: 99%

Impairment of Uric Acid Excretion in Gout*

Lathem

Rodnan²

1962

J. Clin. Invest.

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“…These considerations leave by exclusion the suggestion that the hyperuricemia of those gouty patients who show no overproduction of uric acid may be the result of a reduced capacity to excrete uric acid. Some recent experimental evidence in support of this concept has come from the work of Nugent and Tyler (23) and from this laboratory (24).…”

Section: Column U)mentioning

confidence: 92%

Uric Acid Production in Gout

Seegmiller¹,

Grayzel²,

Laster³

et al. 1961

J. Clin. Invest.

207

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“…Although a lack of specificity and precision of the calorimetric procedure for determining uric acid seriously hampered earlier studies (3), more recent studies with a more specific method have also failed to show significant differences in the urate/inulin clearance ratios between normal and gouty subjects (4). Only in a recent study, when normal subjects were given a diet high in purines in order to raise their serum urate to levels comparable with those of gouty subjects, were all of the six gouty subjects found to have urate/inulin clearance ratios significantly lower than those of normal subjects (5).…”

mentioning

confidence: 95%

The Renal Excretion of Uric Acid in Gout

Seegmiller¹,

Grayzel²,

Howell³

et al. 1962

J. Clin. Invest.

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The hyperuricemia of gout of necessity results from either an excessive production of uric acid or a diminished elimination of uric acid either by the kidney or by means of uricolysis. Behind the controversy of the past century as to which of these explanations is true has been the implicit assumption that only one of them could be correct and that all gouty subjects must carry the same basic metabolic defect if we could but detect it.In a previous study the production of uric acid by 16 gouty patients was evaluated by determining both the extent to which isotopically labeled glycine was incorporated into urinary uric acid and the urate turnover as revealed by the simultaneous injection of uric acid labeled with a different isotope (1). The latter measurement also permitted a correction to be made for the extrarenal disposal of uric acid, as shown by the fraction of injected isotopically labeled uric acid that failed to be recovered in the urinary uric acid. Excessive uric acid production was found in a substantial number of the gouty patients studied, in some of whom all parameters of urate synthesis were elevated several-fold above normal. Five gouty patients were found, however, in whom the glycine incorporation values were in the same range as that found in nongouty control subjects even when corrections were made for the extrarenal disposal of uric acid. The normal urate turnover values of this group of patients provided an independent conifirmation of a normal uric acid production. In addition, there was no evidence of a diminished uricolysis to account for the hyperuricemia of this group of patients. We were therefore left with the view, by exclusion, that a specific impairment in the renal excretion of uric acid must be responsible for the hyperuricemia of this group of gouty patients.In the past, repeated attempts to demonstrate a characteristic difference in the renal handling of uric acid between groups of normal and gouty patients have been unsuccessful (2). Although a lack of specificity and precision of the calorimetric procedure for determining uric acid seriously hampered earlier studies (3), more recent studies with a more specific method have also failed to show significant differences in the urate/inulin clearance ratios between normal and gouty subjects (4). Only in a recent study, when normal subjects were given a diet high in purines in order to raise their serum urate to levels comparable with those of gouty subjects, were all of the six gouty subjects found to have urate/inulin clearance ratios significantly lower than those of normal subjects (5).The present investigation was undertaken in an effort to confirm the postulated decrease in the renal excretion of uric acid in the group of five gouty patients in whom other causes of hyperuricemia had been excluded. In addition, we wished to evaluate the extent to which a diminished renal excretion of uric acid might be contributing to the hyperuricemia of the group of gouty patients in whom an adequate cause for hyperuricemia-i.e., excessive ...

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The Renal Excretion of Uric Acid in Patients With Gout and in Nongouty Subjects *†

Cited by 128 publications

References 16 publications

Impairment of Uric Acid Excretion in Gout*

Impairment of Uric Acid Excretion in Gout*

Uric Acid Production in Gout

The Renal Excretion of Uric Acid in Gout

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