The acute effects of furosemide, ethacrynic acid and chlorothiazide on the renal tubular handling of uric acid in the chicken.

Birds resemble man in that both lack uricase and therefore uric acid (urate) is the end product of purine metabolism in both animals. Although urate is largely excreted by the kidneys in both species, it has generally been accepted that the renal handling of urate in the chicken differs from that in man in that drugs which are known to be uricosuric in man do not produce a uricosuric response in birds. This suggests that tubular reabsorption of urate is either minimal or lacking in birds. The present study used the in vivo Sperber chicken technique to investigate the acute effects of diuretics which are known to alter urate clearance in man. Our results show that both ethacrynic acid and furosemide can selectively increase the apparent tubular excretion of [14C]urate, suggesting that the chicken kidney is capable of reabsorbing urate. Chlorothiazide is known to decrease urate clearance in both man and the chicken and was found in this study also to decrease the renal tubular excretion of [14C]urate formed within the chicken kidney during infusion of [14C]hypoxanthine or [14C]guanine.

Quantification of renal uric acid synthesis in the rat.

The excretion of nephrogenic uric acid in the urine of Sprague-Dawley rats was estimated by use of the isotope-dilution technique. In nonfasted rats the urine-to-plasma specific activity ratio (SAR) of [14C]uric acid was 0.93, suggesting that a minimum of 7% of the uric acid excreted in the urine is synthesized in the kidney. During hypoxanthine infusion the SAR decreased in a dose-related fashion, indicating that the rat kidney is capable of synthesizing relatively large amounts of uric acid and that circulating precursor levels may in part regulate the renal synthesis of uric acid. During allopurinol infusion the SAR increased to 1.0, demonstrating that the SAR is a valid indicator of the contribution of nephrogenic uric acid excreted into the urine. Results of perfusion studies in isolated rat kidneys suggest that uric acid is the major end product of purine catabolism in the rat kidney and that some uric acid formed in the kidney may be absorbed directly into the circulation.

Resin hemoperfusion in dogs intoxicated with ethychlorvynol (Placidyl).

Kinetic parameters were studied to determine the effectiveness of hemoperfusion in removing ethychlorvynol from the plasma and red blood cells (RBC) of intoxicated dogs. Perfusion columns contained polystyrene/divinyl benzene resin (XAD-4 Amberlite. Column clearances of ethchlorvynol averaged 96.5 +/- 0.4% of the plasma flow rate (mean +/- SEM, 9 dogs). Plasma ethchlorvynol t 1/2's during preperfusion periods averaged 94.1 hr. During hemoperfusion, t 1/2's averaged 3.8 hr, or 90.3 hr shorter than at the endogenous rate of detoxication. There was no significant difference between preperfusion and postperfusion half lives. An estimate based on plasma column clearance suggests that 1.5 +/- 0.1 g ethchlorvynol, or 19.0 +/- 2.8% of the dose, was removed by hemoperfusion. The amount eluted from the resin was 2.9 +/- 0.3 g (37.2 +/- 5.8% of the dose), or about twice the amount apparent from plasma clearance alone. Further, the volume of distribution of ethchlorvynol was 2.3 +/- 0.2 liters/kg, suggesting significant distribution to intracellular and extravascular compartments. The results show that resin hemoperfusion removes a large fraction of ethchlorvynol from intoxicated dogs, and greatly adds to endogenous mechanisms for elimination. Ethchlorvynol was removed from RBC directly, and ultimately from extravascular sites as well.

Localization of renal tubular uric acid transport defect in gouty chickens.

Chickens genetically selected for high incidence of articular gout and hyperuricemia were used to determine the site of defective uric acid (UA) transport in gout. The Sperber technique was used to compare the tubular secretion of preformed UA with the tubular secretion of UA formed within the tubular cells in gouty and nongouty chickens of the same strain. In gouty chickens, the tubular excretion ratio of preformed [14C]UA was 36% of the value obtained in nongouty chickens of the same strain, whereas the tubular excretion ratios of [14C]UA formed within the tubular cells from [14C]guanine were equal in the two types of chickens. This suggests that a UA transport is located at the peritubular membrane and that this mechanism is defective in gouty chickens. In addition, the transport of p-aminohippurate (PAH) was normal in gouty chickens, which suggests that the transport mechanism for UA is distinct from that for PAH.