Renal Tubular Secretion Of Urate Research Articles

Hypouricemia Due to Increased Tubular Secretion of Urate in Children with Amanita phalloides Poisoning

The tubular transport of urate was studied in 20 children poisoned with Amanita phalloides and in control group. The aim of this study was to investigate the cause of repeatedly observed episodes of hypouricemia in patients after A. phalloides poisoning. A significant negative correlation between serum uric acid concentration and fractional excretion of urate in poisoned and control groups (r = 0.73, p < 0.001) was found. The results of pyrazinamide and probenecid tests performed in patients after A. phalloides poisoning indicated that hyperuricosuria was most likely due to an increment in renal tubular urate secretion, and not due to decreased presecretory and postsecretory reabsorption of uric acid. These findings indicate that hypouricemia found after A. phalloides poisoning in children is of renal origin due to an increase in tubular urate secretion.

Cause of persistent hypouricemia in outpatients.

We measured serum urate in 3,258 Japanese outpatients. Five of them had persistent hypouricemia. Three also had microhematuria. Four of the five patients were proven to have renal uricosuria with hypouricemia, but otherwise normal tubular function. When tested with both pyrazinamide and benzbromarone, 1 patient had a presecretory reabsorption defect, 2 had postabsorption defects, and 1 an enhanced renal tubular secretion of urate. These results suggest that persistent hypouricemia in outpatients is of very low incidence, is usually caused by an isolated metabolic error of urate transport, and is not related to drug ingestion or systemic disease.

Hypouricemia and Renal Tubular Urate Secretion-Reply

In Reply. —Sanz et al presented an interesting combination of recurrent nephrolithiasis and hypouricemia probably due to increased uric acid secretion. During the past two years, I have encountered five patients with hyperuricosuria due to enhanced uric acid excretion. Three patients had persistent hypouricemia due to an increment in renal tubular urate secretion (of whom two were described in the OctoberArchives). They showed abnormal oral glucose tolerance test results and two of them required treatment for diabetes. The remaining two patients had a syndrome of inappropriate secretion of antidiuretic hormone (SIADH). When their serum sodium levels were decreased, their serum uric acid level fell and excretion of uric acid increased. Pyrazinamide and probenecid therapy was administered and the results were compatible with an increment in renal tubular urate secretion. In diabetes, as well as in SIADH, increased uric acid excretion brings about the lower serum uric acid level. 1-5

Hypouricemia and Renal Tubular Urate Secretion

Hypouricemia and Renal Tubular Urate Secretion

Hypouricemia due to an Increment in Renal Tubular Urate Secretion

Two patients had hypouricemia due to increased uric acid clearance. Their daily urinary uric acid excretions were normal. In both patients, pyrazinamide decreased urinary uric acid clearance to almost while probenecid increased it markedly. No other renal tubular or metabolic abnormalities were found. The serum electrolytes and the urinary electrolytes excretions showed no abnormalities. It appears that increased secretion of uric acid in the renal tubule is most probably responsible for hypouricemia in these patients. This report adds to the list of hypouricemic conditions due to a new isolated renal tubular abnormality.

Determination of tubular secretion of urate in healthy and gouty men.

Recently, a number of clinical and pharmacological observations have provided evidence for two reabsorptive sites for urate within the nephron, one proximal to and one distal to the secretory locus.1–6 Our own data conform to a four-component system for the renal handling of urate, involving complete filtration of uric acid at the glomerulus, reabsorption of 99.3% of the filtered load, secretion further distal in the nephron, and reabsorption of the majority of secreted urate.7 This reference should be consulted for details of the studies on renal tubular secretion of urate.

Renal Tubular Secretion of Urate in Sheep

SummaryThe simultaneous renal clearances of endogenous urate and of inulin were measured in five normal ewes, three pregnant and two not, and in two sheep moribund with ovine toxemia of pregnancy. The urate clearance exceeded the inulin clearance in every period in each sheep, with the ratio ranging from 1.7 to 3.2 and averaging 2.46.

Renal function changes in laying hens fed on dried poultry manure.

1. Renal function was studied in laying hens which had been fed on diets containing 0 (controls), 10 or 20% dried poultry manure (DPM) for one year. 2. Birds fed on 20% DPM showed increased rates of effective renal plasma flow and increased renal tubular secretion of urate during the infusion of large amounts of urate. 3. Renal hypertrophy was not detected in any group.

Pyrazinamide suppression of the uricosuric response to sodium chloride infusion.

Abstract In order to assess the importance of renal tubular secretion of urate in the generation of certain uricosuric states, without the possibility of drug-drug interaction being present, the uricosuric response to a 3 per cent NaCl infusion was investigated in 10 normal men. In the 5 persons who manifested a significant uricosuric response during 3 per cent NaCl infusion, repeat studies conducted after pretreatment with pyrazinamide (PZA) showed significantly diminished changes in urate excretion and clearance. Changes in the absolute and fractional excretions of sodium during 3 per cent NaCl loading were not siginficantly different after PZA. The other subjects, who did not manifest a significant uricosuric response to 3 per cent NaCl infusion, had significantly diminished natriuretic responses when compared to the uricosuric group. Assuming a predominately antisecretory action of PZA, these results suggest an important role for intact tubular secretion in the normal uricosuric response to 3 per cent NaCl. Since the stimulation of tubular urate secretion by NaCl loading is unlikely, an alternative explanation is that 3 per cent NaCl infusion may facilitate the excretion of secreted urate by decreasing urate reabsorption at a postsecretory reabsorptive site.

Urate secretion in man: the pyrazinamide suppression test.

The relatively specific inhibition of the renal tubular secretion of urate after pyrazinamide administration has been used to estimate the contribution of tubular secretion to the urinary uric acid. Recent studies in animals, and other indirect data in man, suggest that the tubular secretion of urate may precede its reabsorption within the nephron and that some secreted urate subsequently is reabsorbed. In addition, the intrarenal secretory and reabsorptive fluxes for urate probably are far greater than previous estimates suggest. Although the pyrazinamide suppression test may still help to estimate the role of tubular secretion in promoting urate excretion, current evidence suggests that it greatly underestimates the magnitude of transport processes because of their interaction.

Evidence for a postsecretory reabsorptive site for uric acid in man.

The effects of administration of drug combinations on uric acid excretion were studied in order to test the hypothesis that a portion of renal tubular reabsorption of uric acid occurs distal to the uric acid secretory site. Oral administration of pyrazinamide (3 g) during probenecid uricosuria (probenecid 500 mg every 6 h) decreased urate excretion from 463 mug/min following probenecid medication alone to 135 mug/min following probenecid plus pyrazinamide (P < 0.01). When a greater uricosuric effect was induced with a 2 g oral dose of probenecid, the decrement in urate excretion which followed pyrazinamide administration (3 g) was more pronounced (2,528 mug/min following probenecid alone, 574 mug/min following probenecid plus pyrazinamide). Results were similar when an 800 mg oral dose of sulfinpyrazone was given in place of probenecid (1,885 mug/min following sulfinpyrazone alone, 475 mug/min following sulfinpyrazone plus pyrazinamide). Thus, apparent urate secretion (measured as the decrease in excretion of urinary uric acid resulting from pyrazinamide administration) appeared to vary, depending upon the degree of inhibition of reabsorption produced by probenecid or sulfinpyrazone. When small doses of aspirin were administered in place of pyrazinamide to produce secretory inhibition, the results were similar. Neither probenecid nor pyrazinamide significantly altered urate excretion when administered to patients with serum salicylate levels above 14 mg/100 ml. These results are interpreted as suggesting that renal tubular reabsorption of uric acid occurs at least in part at a postsecretory site and that a portion of secreted urate is reabsorbed. During maximum probenecid- or sulfinpyrazone-induced uricosuria, inhibition of urate secretion with either pyrazinamide or low doses of aspirin resulted in a decrease in uric acid excretion which exceeded total urinary uric acid during control periods by two- to fourfold. This suggests that renal tubular secretion of urate may greatly exceed uric acid excretion and that a large fraction of secreted urate is reabsorbed. The pyrazinamide suppression test underestimates urate secretion. Uricosuria induced by some drugs, including probenecid, sulfinpyrazone, and iodinated radioopaque dyes, appears to represent, at least in part, inhibition of postsecretory urate reabsorption.