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.

Renal venous portal contribution to PAH and uric acid clearance in the chicken.

The contributions of the renal venous portal and the renal arterial circulations to the renal clearance of p-aminohippuric acid (PAH) and uric acid were determined in the unanesthetized chicken by the simultaneous use of the urinary clearance technique and the Sperber preparation. The [3H]PAH apparent tubular excretion fraction (ATEF) and the clearance of inulin (CIn) were used as indicators of the renal portal and renal arterial contributions, respectively, in a planar equation for total PAH clearance. This equation accurately reflects the renal clearance of PAH as well as the renal venous portal and renal arterial contributions to the total renal clearance of PAH. The equation suggests that under normal conditions approximately 50% of the renal clearance of PAH or uric acid comes from the renal venous portal circulation, with the remaining 50% coming from the arterial circulation. An inverse hyperbolic relationship between the filtration fraction (CIn/CPAH) and the [3H]PAH ATEF was found, demonstrating that the filtration fraction in the chicken decreases from a value of 18 to approximately 6% as the renal portal plasma flow increases from zero to a maximum value. Our equation for total clearance was also used with results of experiments on inhibition of uric acid excretory transport by L- and D-dopa and by probenecid to locate the probable sites of action of those inhibitors.

The evaluation and applications of hemodialyzers for pediatric patients.

It is difficult to determine which pediatric hemodialyzer to use in a given clinical situation since there is no comprehensive comparison of pediatric hemodialyzers. We evaluated five currently available disposable pediatric hemodialyzers in vitro and in vivo during treatment of pediatric patients. Two dialyzers, Gambro Mini-Minor and Viva Cell 0.2 are well suited to small pediatric patients weighing less than 10 kg. Three of the dialyzers are well suited to the pediatric patients weighing greater than 10 kg (Gambro Minor, Cordis Dow 0.6, Viva Cell 0.5). By considering the clinical status of the child and the performance characteristics of the dialyzer (solute removal, priming volume, ultrafiltration, etc.) it is possible to employ a hemodialyzer which more precisely meets the needs of the child without increasing risk factors associated with pediatric hemodialysis.

The Lundia Mini-Minor: a disposable dialyzer for hemodialysis of very small patients.

We have in vitro and in vivo tested the new Gambro Lundia Mini-Minor pediatric dialyzer with the 17 micron membrane. By utilizing blood tubing sets of different volumes in conjunction with the Lundia Mini-Minor we feel that this dialyzer is well suited to use in pediatric patients weighing less than 16-23 kg. During the last 4 years, with the development of improved equipment and techniques, it has become increasingly easier to hemodialyze children and infants with end-stage and acute renal failure [1,2]. We have previously reported our experience with hemodialyzers designed especially for children and babies [1-5, 13, 14]. This report concerns our experience with a new disposable pediatric hemodialyzer, the Lundia Mini-Minor, which has been designed for the smaller pediatric patient weighing less than 16 kg.

Hemodialysis in diabetics: complications in insulin-dependent patients accepted for renal transplantation.

The hemodialysis complications in 67 insulin-dependent diabetic patients accepted for renal transplantation were compared with those in 67 nondiabetic hemodialysis patients. Eleven of the 67 diabetic patients died before receiving a renal transplant-four of myocardial infarction, three of dialysis-related causes, and four of infections. One of the 67 nondiabetic patients died of infection before transplantation. The diabetic patients experienced more complications on dialysis than did the nondiabetic patients; they were more hypertensive and required more ultrafiltration during dialysis. In addition, the diabetic patients had a higher incidence of hypertensive episodes during dialysis, as well as a high incidence of predialysis hyperglycemia. These findings suggest that diabetic patients with renal failure should be dialyzed more frequently and transplanted as soon as possible in order to decrease the complications associated with hemodialysis.

Kidney transplants in patients over 50.

Patients with end-stage renal failure shouldn't be denied the only possibility of cure just because they're old or have other chronic diseases. In this study of 69 patients over age 50-the largest series reported from a single medical center-kidney transplants from related donors had the same high rate of success as in younger patients. Over 80 percent of the patients who received kidneys from their children or siblings are still alive, in contrast to 52 percent of those who had to settle for a cadaver kidney. Infection posed the most serious hazard after surgery. Late complications, particularly hypertension and diabetes, were easily controoled and by no means debilitating. Four of the survivors still need hemodialysis, but over two-thirds have recovered completely.

Etiology and prognosis in acute post-transplant renal failure.

During the last seven years we encountered 117 cases of acute renal failure after 492 renal transplants. The affected patients fall into two general groups that can be broadly identified by an 131I-Hippuran renogram: Those in whom low or no uptake is evident on the renogram (group 1) and those in whom good uptake is evident on the renogram (group 2). Fifty per cent of the patients in group 1 have renal arterial thrombosis or hyperacute rejection. These patients should have a renal arteriogram, and immediate nephrectomy may be necessary. The prognosis in these patients is very grave. In group 2, 89 per cent of the patients have acute tubular necrosis, and they do not differ prognostically from patients who experience immediate renal function. Invasive diagnostic procedures should be avoided in this group because they may increase the mortality rate. We believe that repeated renograms, a reduction in azathioprine dosage and careful dialysis is the only treatment necessary.

Synthesis of uric acid in isolated normothermic perfused mongrel and Dalmatian dog kidneys.

Renal synthesis of uric acid (urate) in the dog was demonstrated by use of two isolated kidney preparations during pulsatile perfusion at 37 degrees C with artificial perfusate or with a plasma fraction. During perfusion of mongrel and Dalmatian dog kidneys with 0.5 mg of [14C]xanthine per 100 ml, a mean of 24.3 and 25.4 mug of [14C]urate per minute, respectively, entered either urine or perfusate after its synthesis in the isolated kidney. Approximately 6.2% of the combined extracellular radiolabeled urate formed in the isolated mongrel kidney was excreted in the urine and 15.7% in the urine of isolated Dalmatian dog kidneys. Recirculating the perfusate without the kidney did not convert any radioactively labeled xanthine to urate and therefore the radioactively labeled urate appearing in the urine and recycled perfusate must have been formed in the renal parenchyma. Renal synthesis of urate was blocked by the xanthine oxidase inhibitor allopurinol. In the presence of allopurinol, [14C]xanthine was excreted unchanged into the urine.

Effects and complications of high efficiency dialysis.

Two and three Dow Cordis Hollow Fiber and Gambro Lundia artificial kidneys were used for high efficiency dialysis in large patients, intoxications, and for rapid ultrafiltration. BUN clearances of up to 240 ml/min were achieved. One episode of severe neuropathy occurred during high efficiency dialysis, and hypotensive episodes were more common. High efficiency dialysis has certain indications particularly in intoxication cases. However, because of possible side effects more experience is needed before its ultimate place in the treatment of uremia can be ascertained.