The Renal Mechanism for Urate Excretion in Man 1

Abstract

The renal mechanisms by which urate is excreted have not yet been defined and there still is disagreement on several major points.Previous studies are in accord on one point, that the normal urate clearance in man is only a small fraction of the glomerular filtration rate, usually of the order of 8-10o. Differing explanations for the relatively low clearance have been offered. Patently, the difference between the clearance of urate and the clearance of inulin must be due either to non-filterability of a large fraction of the plasma urate, to tubular reabsorption of a major fraction of the filtered urate, or to some combination of these two.Some observers have reported non-filterability of the plasma urate, presumably due to proteinbinding or polymerization, but the magnitude of the bound fraction, 4-24%o (1), and 23% (2) has not been nearly sufficient to account for the difference between the clearances of urate and inulin. In a number of other studies (3)(4)(5) Despite this evidence of filterability in sitro and, at least in lower vertebrates, in s'ivo, several investigators have held that this is not the situation in man and that the actual amount filtered at the glomerulus is close to the amount excreted. Berglund and Frisk (9) advanced this theory to explain the fairly constant clearance of urate over a moderate range of plasma urate concentrations and a fairly constant ratio of urate to creatinine clearance in a series of patients with a wide range of renal functional impairment. The same hypothesis has been more recently supported by Wolfson and his associates (2, 10, 11), for reasons similar to those of Berglund and Frisk. In addition, it was suggested that the very low cerebro-spinal fluid urate concentration was due to non-filterability in vivo. The latter position, however, is not tenable since the composition of spinal fluid departs in several respects from that of a plasma ultrafiltrate, the concentration of a number of filterable substances in the spinal fluid being appreciably lower than that in plasma water (12, 13). These authors hypothesize that non-filterability of urate is due to polymerization and that urate is excreted by filtration only or by filtration with a small amount diffusing back passively.The most extensive work on the mechanism of uric acid excretion is probably that of Talbott (14) who reported a number of simultaneous determinations of inulin and urate clearances and the effect of various agents on the clearance ratio. Benedict's method (17). No correction for non-uric acid chromogen was made in any of these experiments since all critical data were obtained at times when the plasma concentration and urinary excretion of urate had been greatly increased by the administration of solutions of pure urate. At such times the non-uric acid chromogen is a negligible fraction of the total. Complete diffusibility of the plasma urate has been assumed in all calculations. Toxic reactionsNausea and vomiting occurred in about half of the patients who received infusions of the lithium carbon...

The Renal Tubular Response to Amino Acid Loading 1

“…In subject BVS experiments (WRR and DMS) only amino acids representative of the types with high (histidine, serine, and threonine) and low (leucine, lysine, and valine) clearance values were measured. The infusion of glycine in all three experiments was accompanied by an increase in the clearances of serine and threonine in addition to that of glycine (Table IV (9) and xylose in the dog (10). Reabsorption itself most certainly involves "active transport" and as such requires energizing reactions.…”

Impairment of Uric Acid Excretion in Gout*

“…If we assume a filtration-reabsorption hypothesis as the mechanism of uric acid excretion (13), the results presented in Tables V and VI and Figure 3 may be interpreted as indicating that both the rate and capacity of tubular reabsorption of urate are augmented in patients with gout. If, on the other hand, urate excretion is conceived of as occurring by a process of tubular secretion (11), the results of the present study can be explained on the basis of impaired secretory activity.…”

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

“…It is usually stated that the plasma uric acid is completely filterable by the glomeruli, that a varying proportion of the filtered uric acid is reabsorbed by the renal tubules and that none is excreted by the tubules (16). There is considerable experimental evidence that plasma uric acid is completely filterable (17).…”