Search PubMed⌕ Search

Biomedical subjects

A Spitzer

Publications and source records attributed to A Spitzer.

At least 91 records · Page 5Linked to original sources

The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents.

The formula GFR = kL/Pcr can be used to estimate GFR in infants, children, and adolescents who have grossly normal body habitus and are in steady-state condition. GFR is expressed in ml/min per 1.73 m2 BSA, L represents body length in cm, Pcr represents plasma creatinine concentration in mg per dl and k is a constant of proportionality that reflects the relationship between urinary creatinine excretion and units of body size. The value of k varies as a function of age and sex being 0.33 in preterm infants, 0.45 in full-term infants, 0.55 in children and adolescent girls, and 0.70 in adolescent boys. The advantages of rapid determination, reasonable accuracy, and the avoidance of urine collection justify the use of this formula in pediatric patients.

Adolescent↗

Factors affecting proximal tubular reabsorption during development.

Studies performed in several animal species have demonstrated that glomerulotubular balance is maintained throughout development despite the many changes that occur in the factors known to control it. In an attempt to understand the nature of this phenomenon we quantified the magnitude and described the profile of these changes in guinea pigs. The changes in physical forces were assessed from measurements of hydrostatic and oncotic pressures, whereas those in the permeability characteristics of the proximal tubule epithelium were estimated from permeance to macromolecules of graded radii, histologic measurements of the intercellular channels, and measurements of end-proximal ratio of tubular fluid-to-plasma osmolality (TF/Posm). Between 1 and 50 days of age the net pressure for reabsorption increased from 15.0 to 30.9 mmHg (P less than 0.01, n = 15) with the major change occurring during the first 2-3 wk of postnatal life. The urinary recovery of inulin, sucrose, and creatinine, injected in the early segment of proximal tubules did not vary with age. The urinary recovery of mannitol (MW 180 daltons, Stokes-Einstein radius 4.0 X 10(-10) m) increased from 92% at birth to 100% at 49 days of age (P less than 0.001, n = 24), consistent with a decrease of approximately 0.5 X 10(-10) m in the luminal openings of the paracellular channels. The length of the zonulae occludens and the width of the intercellular channels did not change during this period; however, the length of the channels increased from 5.0 +/- 0.17 to 8.9 +/- 0.48 micron (P less than 0.01, n = 16). These changes should result in an increase in resistance across the intercellular channels. Consistent with this assertion is the observation that the mean TF/Posm of the fluid collected toward the end of the proximal convoluted tubule decreased as a function of age from 1.05 at day 2 to 0.98 at day 80 (P less than 0.001, n = 24). The findings support the hypothesis that during early postnatal life glomerulotubular balance is made possible by a high permeability of the proximal tubule, which compensates for the low net reabsorptive pressure. As the animal matures and the proximal tubule epithelium becomes tighter, for glomerulotubular balance to be maintained, an increase in the number of intercellular channels and in the active transport of sodium need to be postulated.

Aging↗

NMR measurement of intracellular water volume in rat kidney proximal tubules.

Knowledge of cell water volume is essential for the measurement of concentrations of intracellular ions and metabolites in kidney proximal tubules. We have developed a method which utilizes 35Cl-NMR as a measure of extracellular volume and 2H-NMR, in combination with a membrane-impermeable shift-reagent [Dy-DTPA]2-, as a measure of the ratio of intra- and extracellular water volumes. Measurement of extracellular volume by 35Cl-NMR is possible, since the resonance of intracellular 35Cl is too broad to be detectable in kidney cells. The 2H-NMR measurement exploits the fact that only extracellular water is in direct contact with [Dy-DTPA]2-. However, rapid exchange of water across the cell membrane results in only a single 2H2O resonance at a chemical shift which is a weighted average of the shifted extra- and unshifted intracellular water resonances. Expression of the extracellular volume as a fraction of the total volume by fCl and as a fraction of the total water-volume by fD, permits the calculation of the fractional cell-water content fw = [(1/fD)-1]/[(1/fCl)-1]. This approach was applied to proximal tubular suspensions prepared from the rat kidney. The water content was found to be 76.9 +/- 1.8% (n = 6) at 37 degrees C. Increasing extracellular osmolality from 295 to 390 mOsm/kg H2O, by addition of mannitol, decreased the water content by 21%. Our results are in good agreement with those obtained by the gravimetric method.

Animals↗

23Na NMR spectroscopy of proximal tubule suspensions.

Intracellular sodium concentrations in proximal tubule suspensions of rat kidney were measured by NMR spectroscopy. A simple method for the preparation of proximal tubule suspension is described. Examination by light microscopy revealed these preparations to contain 93.6 +/- 0.6% (N = 5) proximal tubules, and electron microscopy demonstrated that the tubules were open. When incubated with trypan blue for five min, only 2% of tubules picked-up the dye. The basal oxygen consumption rate was 0.42 +/- 0.01 microliter min-1 mg protein-1 (N = 6). Addition of succinate (5 mM) resulted in a fivefold increase in the rate of oxygen consumption. The 23Na spectra were obtained in proximal tubules incubated for 30 min in the aqueous shift reagent dysprosium tripolyphosphate Dy(PPPi)2(7-). The NMR observable sodium concentration was 34.1 +/- 1.8 mM at room temperature and 16.3 +/- 0.6 mM (P less than 0.001) at 37 degrees C. Addition of ouabain (10(-4) M) at 37 degrees C resulted in an increase in intracellular sodium to 30.9 +/- 2.9 mM (P less than 0.001), while nystatin increased the concentration of sodium to 72.0 +/- 9.1 mM (P less than 0.001), compared to basal concentration. Thus NMR permits the measurement of intracellular concentration of sodium in proximal tubules under basal conditions and to monitor, in the same preparation, the changes that occur under various experimental conditions without interfering with the morphologic integrity of the cells.

Animals↗

Renal reabsorption of phosphate during development: whole-kidney events.

The isolated perfused kidney of the guinea pig has been used to assess the mechanism that accounts for the maintenance of the positive phosphate (Pi) balance during development. The kidneys obtained from mature guinea pigs (n = 25) had a glomerular filtration rate (GFR) of 0.48 +/- 0.04 ml/min (mean +/- SE), whereas those of the newborn (n = 20) had a GFR of 0.15 +/- 0.02 ml/min. These values compare favorably with those observed in intact animals. The fractional excretion of Na+ (FENa) was 3.8 +/- 0.7% in the mature kidneys and 4.7 +/- 0.7% in the newborn kidneys. The maximal tubular reabsorption of Pi (TmPi) by the newborn kidney was 24.3 +/- 2.8 micrograms/min. The filtered load at which the TmPi of the newborn was reached exceeds by 2.5-fold the filtered load of Pi encountered under physiological conditions. In the adult the TmPi was 53.9 +/- 2.6 micrograms/min. The filtered load at which the TmPi of the adult was reached is only slightly higher than the average normal filtered load of Pi. The TmPi/GFR was significantly higher (P less than 0.02) in the newborn (117.4 +/- 10.8 micrograms X min-1 X ml-1 GFR) compared with the adult (82.6 +/- 3.6 micrograms X min-1 X ml-1 GFR). Moreover, at any filtered load of Pi below Tm the newborn animals reabsorbed twofold more Pi per gram kidney weight than the adult (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Glomerular capillary permeability in developing canines.

The changes in glomerular permeability that occur during development were assessed in 1- and 6-wk-old canines by analyzing dextran-sieving curves obtained in six animals at each age. The fractional clearance of the smallest dextran molecules (18 A) was 0.97 +/- 0.02 (+/- SE) in both 1- and 6-wk-old animals, and it became progressively less at larger molecular sizes. The sieving curves were consistent with an isosporous model of a glomerular capillary. When axial changes in protein concentration were included in the mathematical model, the apparent pore radius was 62.7 +/- 1.7 and 61.7 +/- 1.69 A in 1- and 6-wk-old puppies, respectively (P greater than 0.7). The effects of developmental changes in hydrostatic pressure and renal blood flow were balanced by the increases in serum protein concentration and filtration fraction leaving the fractional clearances of macromolecules unchanged. In contrast, the total cross-sectional pore area per unit path length (Aw/delta x) increased during this 6-wk period by approximately 7.5-fold (from 1.39 +/- 0.2 to 10.55 +/- 3.0 10(-5) cm, P less than 0.0001), and the ultrafiltration coefficient rose from 0.012 +/- 0.002 to 0.093 +/- 0.012 ml X s-1 X mmHg-1 (P less than 0.0001). The findings reveal constancy of pore size and an increase in total pore area as a function of age. Analysis by classical pore theory yielded similar findings. We conclude that the predominant factor determining the rise in glomerular filtration rate during development is the large increment in Aw/delta x, which in turn is due to increases in the surface area and pore density of the glomerular capillaries.

Animals↗

Prealbumin as a biochemical marker of nutritional adequacy in premature infants.

To determine whether serum prealbumin would be useful in identifying adequacy of protein and calorie intake in premature infants, 17 infants between 26 and 33 weeks gestational age were studied throughout hospitalization. Serial anthropometric measurements, nutritional intake, and serum prealbumin concentrations were correlated. When mean intake of calories and protein was lower than 100 kcal/kg/day and less than 2 gm/kg/day, respectively, there was a significant difference in mean prealbumin values, compared with those in infants with a higher intake (P much less than 0.001). For infants with birth weights of 1000 gm or less, prealbumin correlated with protein intake (r = 0.66) and calorie intake (r = 0.64). In these infants, when protein intake exceeded 2 gm/kg/day, prealbumin concentrations increased to values reported for full-term infants in the first months of life. There was no significant correlation between intake of calories or protein and prealbumin values for infants born weighing greater than 1000 gm. Anthropometric measurements did not correlate with protein or calorie intake. We conclude that prealbumin is a sensitive measure of protein and calorie intake in premature infants, and that the definition of adequate nutrition may be different for premature infants of different birth weights and at various postconceptional ages.

Body Weight↗

Nitrogen mustard therapy in children with frequent-relapsing nephrotic syndrome and steroid toxicity.

Nitrogen mustard (HN-2) is an alkylating agent known to be effective in inducing and prolonging remissions of nephrotic syndrome in children. The fact that the drug is administered intravenously eliminates the problem of compliance, and the fact that the treatment needs to be given only for a few days may lower the incidence of side-effects observed with other cytotoxic agents. We administered HN-2 to 12 children with the steroid-sensitive frequent-relapsing form of nephrotic syndrome, who had evidence of steroid toxicity. Life table analysis reveals a 46% sustained remission rate after 27 mo of follow-up. Complications of HN-2 treatment included only mild thrombophlebitis (2 patients) and mild local paresthesia (1 patient).

Child, Preschool↗

Impact of age on effects of ureteral obstruction on renal function.

Chronic partial ureteral obstruction of the urinary tract is a common congenital abnormality. Yet, its impact on the function of the kidney in the young has not been examined. To determine the relationship between age at the time of injury and outcome, partial ureteral obstruction was produced in guinea pigs during the first, second, third, fourth, or fifth week of life, and several variables of glomerular, proximal and distal tubular functions were measured 4 weeks later. The results were compared with those obtained in the contralateral kidney and with those observed in age-matched sham-operated animals. There was a significant impairment in the growth of the obstructed kidney. The weight of the contralateral kidney in the experimental animals was significantly greater than that of the obstructed (P less than 0.001) or control (P less than 0.005) kidney, but compensatory hypertrophy decreased progressively with age, being 30% of control when the obstruction was produced in the second week of life and only 2% when the obstruction occurred at 5 weeks of age. Obstruction resulted in a marked reduction in GFR at all ages, the impairment being inversely proportional with age. Conversely, the increase in GFR on the contralateral side, which was proportional with the increase in renal mass, diminished from 60.1 to 20.5% (r = 0.96, P less than 0.001) as a function age. Tubular reabsorption of phosphate was significantly lower in obstructed kidneys, particularly so in the animals sustaining obstruction during the first 2 weeks of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Renal failure in childhood.

Renal failure in infants and children requires prompt and thorough diagnostic evaluation for reversible causes and careful medical management. Congenital malformations of the renal parenchyma and urinary drainage system must be excluded in any child, even the adolescent. The management of these patients requires close cooperation with the (pediatric) urologist. These children are at highest risk for the development of complications, such as growth failure, osteodystrophy, and urinary tract infections. Prolonged progressive renal insufficiency in this group must be anticipated. In contrast, acquired renal insults may result in acute, reversible renal failure. Awareness of the hemodynamic or nephrotoxic insults that can result in ARF, and appropriate diagnostic and therapeutic maneuvers, may minimize morbidity and mortality. CRF presents the physician with long-term and complex challenge of medical management. Dietary and drug therapy can be remarkably effective in reducing the complications of CRF. Rehabilitation with successful renal transplantation is an attainable goal for most uremic children.

Acute Kidney Injury↗

The role of the kidney in sodium homeostasis during maturation.

Evidence is presented that the retention of sodium observed during development is consequent primarily to enhanced tubular reabsorption rather than to low rates of glomerular filtration. The enhanced transport of sodium occurs in nephron segments located beyond the proximal tubule, apparently under the stimulation of the high plasma concentration of aldosterone. This adaptive mechanism may account for the fact that the infant thrives on a rather low intake of sodium, as prevails during the period of breast-feeding. The renin-angiotensin-aldosterone system cannot be fully inhibited even by intravascular volume expansion and this may account for the blunted natriuretic response of the developing animal and human to the acute infusion of saline or albumin solutions. Conversely, the renal sodium loss and the hyponatremia often encountered in premature babies appear to be due to an insufficient rise in aldosterone secretion or to a limited responsiveness of the distal tubule to aldosterone stimulation.

Absorption↗

Congenital ingrown toenails: clinical significance.

The great toenails of 302 newborn infants were evaluated to identify a specific conformation which might predispose these children to chronic paronychia. Forty-one infants who appeared to have great toenails impeded by tissue distally were followed for 12 months. All had essentially normal appearing nails by six months of age. None developed chronic paronychia. The results suggest that the changes originally noted were variations in the normal development of the great toenail.

Female↗

The relationship between intravascular volume expansion and natriuresis in developing puppies.

The role played by the relative degree of expansion of the intravascular and extravascular compartments in limiting the natriuretic response of fluid-loaded developing animals was determined in 1-, 2-, 3- and 6-wk-old puppies. Volume expansion was induced by infusing either isotonic saline, 10% body weight or isoncotic albumin in saline 5% body weight, and measurements of glomerular filtration rate, sodium excretion, fractional excretion of sodium, and plasma volume were made. Each expansion procedure resulted in an increase in the absolute excretion of sodium at all ages (P less than 0.001). The greatest natriuretic effect was observed in the 3-wk-old puppies, the average of the two solutions being 19, 30, 70, and 28 muEq/min/kg in the 1, 2, 3, and 6-wk-old animals, respectively. The difference in natriuresis among the age groups was due predominantly to differences in the magnitude of the increase in fractional excretion of sodium. At all ages, a greater absolute excretion of sodium was encountered during volume expansion with saline than observed with albumin (P less than 0.05). The intravascular volume increased by a similar % at all ages (P greater than 0.1), and saline and albumin yielded equivalent degrees of intravascular expansion (approximately 50%). The results demonstrate that age-related changes in natriuretic response to volume expansion cannot be attributed to differences in either the degree of expansion or the distribution of the load. In addition, the observations indicate that the mechanism underlying the difference between the response to isotonic saline and isoncotic albumin in saline is already operative at birth, and that it is independent of nephron heterogeneity since the proportion of superficial nephrons must have changed during the period of nephrogenesis. The collecting duct, which is sensitive to both isotonic saline and isoncotic albumin, is likely to be responsible for the parallel development of the renal response to these two methods of intravascular volume expansion.

Albumins↗

Lead intoxication during development: its late effects on kidney function and blood pressure.

Exposure to lead in early life may result in chronic renal disease in adulthood. To test this hypothesis, we gave Sprague-Dawley rats, from 3 to 9 weeks of age, either tap water or a 1% lead acetate solution, and we studied them (in pairs) 3 and 16 weeks after exposure; that is, at 12 and 25 weeks of age. Lead-intoxicated animals failed to grow. Their GFR's were lower compared with the matched controls and fell between 12 and 25 weeks of age from 4.8 +/- 0.3 to 3.3 +/- 0.4 ml/min/g dry kidney wt (P less than 0.01). Changes in RBF and single nephron GFR were proportional to changes in total kidney GFR, indicating that superficial and deep nephrons were equally affected. The blood pressure in the lead-exposed animals studied at 25 weeks of age was 143.2 +/- 3.7 mm Hg, a value significantly higher than that of 130.4 +/- 3.3 observed in controls (P less than 0.05). These results demonstrate that limited exposure to lead during development can result in progressive renal insufficiency and hypertension.

Animals↗