Nephrotoxic agents such as puromycin aminonucleoside (PAN) and sodium maleate (MAL) have been used to induce experimental glomerular proteinuria and tubular disease, respectively. Current studies show that PAN caused a massive loss of albumin in the urine while not affecting the excretion of the smaller, sex-dependent α_2u-globulin. On the other hand, MAL which inhibits the reabsorption of proteins, increased the loss of both α_2u and albumin. Both nephrotoxic agents increased the excretion of albumin when administered to female rats. MAL-induced proteinuria was used as a direct measure of the renal load for α_2u and albumin. Renal loads and excretion of α_2u and albumin were measured in male rats maintained on 0, 20, and 50% casein diets. On the protein-free diet, the excretion of both α_2u and albumin was reduced (less than 1 mg daily); their renal loads were almost totally reabsorbed. On a 50% casein diet the reabsorption of α_2u was reduced from a normal of 60% to 10% of the renal load. Thus, the high protein diet increased the excretion of α_2u while having little effect on the excretion of albumin. We suggest that dietary protein exerts two levels of control on the excretion of protein in the urine of the adult male rat. Protein-deficient diets stimulate the general reabsorption of proteins thereby minimizing the excretion of α_2u and albumin. High protein diets appear to reduce selectively the reabsorption of α_2u -globulin, thereby increasing its excretion in the urine.

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ExtractThe accumulation of literature on hereditary nephritis with or without nerve deafness attests to the increased awareness of the existence of this syndrome. I t is the purpose of this report to show that there are distinguishing histologic findings in young patients with minimal disease and normal renal function. Eleven patients were studied; 4 were females and 7 were males. Relevant family histories and clinical laboratory findings are shown in table I. I n all patients, hematuria, gross or microscopic, was present. Exacerbations of the hematuria occurred as a part of the exaggerated response of these patients to upper respiratory infection. Renal functional data are shown in table 11. These data were generally within normal limits for our laboratory. Table I11 outlines the morphologic findings observed on renal biopsy. In renal biopsies obtained from 10 patients, there was observed persistence of fetal-like glomeruli characterized by the circumferential crowding of visceral epithelium and an apparent decrease in the number of patent capillaries. The most striking finding in the tubules was the presence of red cells and red blood cell casts seen mainly in the distal and collecting tubules. Foam cells were an infrequent finding but, when present, were unassociated with interstitial fibrosis. Examination of kidney specimens under the electron microscope revealed the presence of at least three glomeruli in seven patients and of fetal-like glomeruli in all patients. There was also circumferential crowding of visceral epithelial cells, particularly at the surface, facing Bowman's capsule. These epithelial cells were characterized by large nuclei, small amounts of cytoplasm, apparently poorly developed intracytoplasmic organelles, and frequent villous-like cytoplasmic projections on the surface. I n families from whom past histories are unavailable, recognition of distinct renal biopsy characteristics would help identify this syndrome in the early stages of disease. At this stage, the combination of morphologic features considered to be characteristic would include the presence of a) fetal-like glomeruli, which were seen by electron microscopy in 7 patients and by light microscopy in 10 patients; b) mild to moderate hypercellularity ; c) large numbers of tubules filled with red blood cells and red blood cell casts; and d) foam cells in the absence of interstitial fibrosis. The fetal-like glomeruli present in our patients did not correspond to any of the normal stages of glomerular development observed under electron microscopy by other investigators, but rather, appeared to represent dysgenesis. Most patients from whom data are reported were more than 2 years of age, at which time fetal glomeruli are exceptional. Of interest was the observation that almost identical histology was found to exist among the siblings. ANTONOVYCH, DEASY, TINA, D'ALBORA, HOLLERMAN a n d CALCAGNO SpeculationT h e fetal-like glomeruli observed o n renal biopsy might b e the result of either a developmental abnormality or dysgenesis. T ...

Administration of the polyene antibiotic, Amphotericin B (AmB) for the treatment of mycotic diseases has been associated with abnormalities of renal function (1). Its chronic administration in man causes a reduction in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) , renal tubular acidosis, natriuresis, and kaliuresis (2). In the dog, acute administration of AmB results in a similar decrease in GFR and E R P F apparently due to active renal arteriolar constriction ( 3 ) . Studies on the toad and turtle bladder indicate that AmB increases the permeability of the membrane to water, urea and electrolytes (4, 5 ) .This study was designed to determine the acute effects of AmB on the renal tubule and on the intrarenal distribution of blood flow. These results confirm the previously demonstrated decrease in E R P F and GFR. I n addition, there was an increase in the fractional excretion of sodium and potassium. Although free water clearance ( C H~O ) was decreased, the free water reabsorption curve ( T C , ,~/ C,,,) was unaffected, suggesting that the effect of AmB is predominantly at the distal tubule beyond the loop of Henle. The decrease in C H~O was probably due to a decreased distal tubular reabsorption of sodium and an increase in membrane permeability to water. Materials and Methods. The experimentswere performed on female mongrel dogs (12-20 kg) during hydropenia or water diuresis.I . Water diuresis. Eleven dogs were included in this study. All food was withdrawn 16-18 hr before the experiment. Water was permitted ad libitum. The animals were anes-1This project was supported in part by US.Public Health Service Training Grant HE 5353. thetized with sodium pentobarbital (30 mg/kg iv). An endotracheal tube was inserted and connected to a mechanical respirator. The femoral vessels were cannulated for blood sampling, fluid administration, and blood pressure recording, A Foley catheter was placed in the urinary bladder; and complete emptying of the bladder was assured by air washout. An oral water load amounting to 57' 0 of the body weight was administered via a gastric tube, and supplemented by an equal amount of 2.5% dextrose in water given intravenously. Water diuresis was sustained by infusing 0.45% saline at 0.5 ml/kg/min. Inulin and p-aminohippurate solution were infused into the femoral vein to permit clearance measurements. After an equilibration period of 45-60 min or when water diuresis was achieved, 2-4 control urine samples were collected at 5-1 5-min intervals. Blood samples were collected at appropriate times. AmB ( 2 mg/kg) was then infused intravenously at a rate of 0.5 mg/min for approximately 30 min. Thereafter, urine was sampled every 10-1 5-min for approximately 1 hr.ZZ. Antidiuresis. There were 5 animals in this group. Thirty-six hr prior to study the animals were deprived of food and water.Sixteen to 18 hr before the experiment, 5 units of pitressin tannate in oil were given intramuscularly. After endotracheal intubation, vessel cannulation and initial blood and urine sam...

ExtractThe present studies were designed to elucidate renal functional changes in infants and children with urinary tract infections. Twenty-three infants and children ranging in age from 4 months to 13 6 / 12 years with urinary tract infections were studied. Four children ranging in age from 2 to 6 10 / 12 years without documented urinary tract infections served as controls. Inulin clearances (Gi) were utilized for measurement of glomerular filtration rate. Renal plasma flow and tubular maximum excretory capacity were ascertained by the intravenous administration of para-aminohippurate (PAH). Second determinations performed in eight patients and a third determination in one patient provided longitudinal follow-up. Renal plasma flow measurements were low in 4 of 6 infants and in 6 of 17 children on initial testing; these decreased values were associated with normal glomerular filtration rates except in 3 subjects. In the 4 patients without documented urinary tract infections, G PAH values were within the normal range. G PAH values obtained initially in all subjects were compared on a surface area basis to those characteristic of normal children. Of the 27 experimental points, 21 were below the line representing the normal average C PAH for children. In this small series, only one of three infants failed to recover this function at the time of repeat testing. The recovery rate was less in the children studied. The data indicate that a decrease in renal plasma flow occurs prior to significant alterations in the other renal functional parameters measured.Twenty-two subjects were tested for both G PAH and Tm P AH-The ratio (G PAH /Tm PAH ) was lower in all three groups than the reported normal value of 7.7. In those patients demonstrating an initially reduced value, 13 of 16 showed normal G PAH values. These findings could represent renal ischemia of proximal tubular tissue.The persistence of renal vascular changes in the face of absent clinical and/or laboratory evidence of urinary tract infections emphasizes the need for caution in identifying the prognosis of children with pyelonephritis and the need for careful long-term evaluation. SpeculationAlthough it has been well documented that the renal medulla is the primary site of involvement in pyelonephritis, the current data suggest that the post-glomerular capillaries and tubular structures in the renal cortex are also early sites of involvement in infants and children. A question raised by the study is the relation of reduced renal plasma flow measurements to the natural history and pathogenesis of recurrent pyelonephritis. It is suggested that agents promoting a change toward normal renal circulation may reverse the pathologic process.