Earlier publications questioned the reliability of measurements of renal plasma flow in young infants, since the extraction ratios for para-aminohippurate (EPAH) used were those obtained in adults (1-3). It was suggested that the use of these high values for EPAH to determine renal plasma flow and filtration fraction might not be valid and could account for the high filtration fraction reported in infants under a year of age (1)(2)(3)(4)(5). This high fraction was interpreted to indicate that the rate of glomerular filtration is greater in comparison to renal plasma flow than that in adults. The present study was designed to measure EPAH in young infants in order to arrive at the true value for renal plasma flow and calculated filtration fraction. METHODSFifteen children between 8 days and 10 years old were studied; eight were under 3 months, and seven between 5 months and 10 years old. Pertinent clinical and laboratory data are listed in Tables I through IV. Forty-five minutes before testing, eight of the fifteen patients were given a sedative; ' five were infants (no. 1 and 5-8) and three were older children (no. 10, 11, and 15). Inulin2 and para-aminohippurate (PAH) were administered in normal saline or 5% dextrose in water after base-line control venous blood determinations were made. The diluent and the intervals from the mixing of PAH with the diluent to the end of the test are recorded in Tables II and III. Saline as the diluent for the PAH injection was used in four infants and in two children. Five per cent dextrose in water was the diluent in four infants and in seven children. Two infants and two children were I Chlorpromazine, 6.25 mg per ml; promethazine, 6.25 mg per ml; and meperidine hydrochloride, 25.00 mg per ml. The dose was 1 ml per 20 pounds of body weight, up to a maximum of 2 ml.2 Kindly supplied by the General Diagnostics Division, Warner-Chilcott Laboratories, Morris Plains, N. J. studied with both diluents. All blood samples were collected in heparinized tubes. Inulin and PAH were given to maintain arterial blood concentrations above 25 mg per 100 ml for inulin and below 4 mg per 100 ml for PAH. These values were not always obtained, but in the four infants given PAH in normal saline, the level of renal arterial PAH was over 3.1 mg per 100 ml in only one period of Patient 1. A no. 10 French catheter was placed in the bladder for urine collections. The femoral artery and vein were catheterized with Birds Eye catheters no. 5, 6, or 7. Under direct fluoroscopic supervision, the right renal vein was entered, and an attempt was made to enter the right renal artery; if it was unsuccessful, arterial blood samples were obtained from the aorta close to the renal artery. Spot films were taken to demonstrate the location of catheters before collections were made. Measurements of glomerular filtration rate and effective renal plasma flow measurements were made in three infants and in one older child. Complete emptying of the bladder was obtained by instilling air, and blood was withdrawn simultaneo...

Our laboratory has characterized dopamine receptors in glomeruli and tubular homogenates. Since the heterogeneity of kidney homogenates limits the interpretation of these studies, the [3H]haloperidol binding site and adenylate cyclase sensitivity to dopamine were studied in the isolated proximal convoluted tubule and pars recta of the rabbit kidney. [3H]Haloperidol binding sites were saturable, stereoselective, and of high affinity. The apparent dissociation constant was 31.5 X 10(-9) M (+/- 8.5) and the maximum receptor density was 0.31 X 10(-15) M (+/- 0.08) per millimeter. In pars recta specific binding was 53% of total [3H]-haloperidol binding. Dopamine stimulated adenylate cyclase activity in a dose-related manner, which was inhibited by cis-flupenthixol but not by trans-flupenthixol or (-)-propranolol. Moreover, the stimulatory effect of the dopamine 1 (D1) agonist SKF 82526 on adenylate cyclase activity was blocked by the D1 antagonist SCH 23390. Dopamine receptors in the proximal convoluted tubule appear to be of the D1 subtype since they are linked to stimulation of adenylate cyclase. This is further substantiated by the stereoselectivity for (+)-sulpiride (a D1 antagonist), which had a greater affinity for the [3H]haloperidol binding site than (-)-sulpiride (a D2 antagonist).

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SummaryTotal serum cholesterol, phospholipids, and triglyceride levels, lipoprotein fractionation, and plasma parathormone levels were measured in a group of 31 nonnephrotic children with various levels of renal function and on hemodialysis. Group A served as controls and consisted of eight healthy children with glomerular fdtration rate (GFR) greater than 110 ml/min/1.73 m2. Group B consisted of six children with GFR of 60 to 95 ml/min/1.73 m2. Group C consisted of nine children with GFR of 10 to 40 ml/min/ 1.73 m2, and group D consisted of eight children on maintenance hemodialysis with GFR of 0 to 5 ml/min/1.73 m2. Among the groups, there were no significant differences in total serum cholesterol and phospholipid levels. A significant ( P < 0.05) increase in triglyceride levels was observed in patient groups C and D.Lipoprotein fractionation revealed a significant increase (P < 0.05) in the pre-beta lipoprotein levels (very low density lipoproteins) in patients in group D with 63% of these patients demonstrating a type IV lipoprotein pattern. There were no significant differences observed in the beta lipoproteins (low-density lipoproteins). However, the alpha lipoproteins (high-density lipoproteins) decreased significantly ( P < 0.05) in patients whose GFR was below 40 ml/min/1.73 m2 (group C) as well as patients in group D.Absolute plasma parathormone levels did not significantly correlate with serum triglyceride levels and remained normal until after the onset of hemodialysis when they increased significantly in all patients. SpeculationEvidence has been accumulating over the past few years that chronic hemodialysis and renal transplant adult patients have shortened survival because of accelerated atherosclerotic cardiovascular disease for which hyperlipidemia could be one of several etiologic factors. Similar epidemiologic studies have not been performed in children. We have demonstrated for the first time in children that alterations in serum triglycerides and alpha lipoproteins (high-density lipoproteins) occur early in chronic renal insufficiency and before the onset of uremia when the glomerular fdtration rate falls below 40 ml/min/1.73 m2. These lipid abnormalities become further aggravated with the onset of hemodialysis. If pediatric renal transplant patients show similar lipid abnormalities, then the potential for cardiovascular complications will be of importance in the early medical management of these children.

It is known that young premature infants are unable to concentrate urine to the same degree as adults. The following hypotheses have been advanced to explain this difference: (a) A lowered production of antidiuretic hormone (1); (b) a re-,duced response of the distal renal tubule (endorgan) to antidiuretic hormone (2); (c) a decreased rate of solute excretion secondary to a lower rate of glomerular filtration (3).Heller and Zaimis found that there is a lower concentration of antidiuretic hormone in the pituitary body of newborn infants than in adults, when compared on a body weight basis (1). Yet these authors believe that in spite of this smaller amount of hormone in the pituitary of the newborn infant, there is still a sufficient quantity of the hormone to produce a maximally concentrated urine, if the hormone is released and if the renal tubule of the newborn infant is responsive. Heller (2) also showed that amounts of pituitary extract, which produced a pronounced inhibition of water diuresis in adults, had only a slight and fleeting effect on the kidney of newborn infants. In comparing the response of three premature infants with that of two adults to intravenously administered pitressin during water diuresis, it was found (4) that the extent and duration of the antidiuretic response was less in the premature infant. The third hypothesis, the effect of solute excretion, can be tested by noting the changes in urine osmolarity in response to solute loading. If the lower concentrating capacity during hydropenia were solely a reflection of the lower solute load in the premature infant, then a rise in the osmolar concentration should occur with loading. On the 'Read in part before the 23rd Annual Meeting of the Society for Pediatric Research, Atlantic City, New Jersey, May, 1953. 2Aided by grants from the Mead Johnson Company, Evansville, Indiana, and the U. S. Public Health Service.other hand, if the response to loading were similar to the adult but of lesser magnitude, it would suggest that the lower concentrating capacity was due to a deficient tubular response. The experiments reported here were planned to test this hypothesis. METHODSThe subjects of these studies were four premature infants weighing approximately 1500 grams but varying in ages from 5 to 23 days. To induce hydropenia they were deprived of water and formula for 12 to 18 hours. Urine aliquots were obtained to determine the maximum urine osmolarity during water deprivation.Mannitol was used as the loading substance and was given in a 25 per cent solution intravenously. During the first 10 minutes, 180 to 200 milliosmoles per 1.73 M' were given and this was followed by a maintenance infusion of 1 per cent of the total priming dose per minute. Fifteen to 20 minutes were allowed for equilibration of mannitol; urine was collected under oil for three or more 10-minute periods. Blood samples were drawn before loading, after equilibration, and after the experiments were completed. The osmotic pressure, sodium, chloride and potassium of the urine and...