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Biomedical subjects

D I Goldsmith

Publications and source records attributed to D I Goldsmith.

13 recordsLinked to original sources
PubMed1986

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↗
PubMed1985

Identification of osmotically active solutes in urine.

Measurement of the fractional excretion of sodium ions (FENa) and the urinary specific gravity (SG) aids considerably in the clinical assessment of fluid and Na+ balance. However, these determinations may not provide meaningful information if the patient has been treated with a diuretic. In particular, osmotic agents can affect circulating volume by causing natriuresis with a relatively high urinary SG, even in the face of volume and Na+ depletion. Two methods used frequently to identify osmotic diuretics were examined for accuracy. A new equation using the last two digits of SG was derived to identify osmotic agents without the need for an independent measurement of osmolality. The new equation was clearly superior to the more traditional formulas in that it identified accurately the presence of sodium diatrizoate, an ionized molecule, in each of 12 samples, whereas this contrast material was detected in only one sample by determining the difference between measured osmolality and the sum of the usual urinary constituents. A simplified version of the new formula was statistically as accurate as the more complex equation.

Child↗
PubMed1985

The effect of captopril on urinary protein excretion in puromycin aminonucleoside nephrosis in rats.

We investigated the effect of captopril, an orally active angiotensin converting enzyme inhibitor, on urinary protein excretion in puromycin aminonucleoside nephrotic rats. The administration of captopril (10 mg/100 g body weight) decreased proteinuria on days 10-14 following the administration of puromycin aminonucleoside (73.0 versus 125.0 mg, p less than 0.01), without affecting glomerular filtration rate. The beneficial effect of captopril was not abolished by the continuous intravenous infusion of angiotensin II (10 micrograms/kg/h for 9 days) or subcutaneous injections of aprotinin (50,000 KIU/day for 3 days). Indomethacin, in moderate (5 mg/kg/day for 3 days) or high (10 mg/kg/day) doses, abolished the captopril attenuation in urinary protein excretion. The salutory effect of captopril was characterized by a reduction in the fractional excretion of protein without compromising the glomerular filtration rate. No difference in renal ultrastructure was noted in captopril-treated versus control animals. Captopril was ineffective in reducing urinary protein excretion in rats with adriamycin-induced glomerulopathy. We conclude that captopril acts to reduce proteinuria in renal disease states arising from depletion of the glomerular basement membrane polyanion. The mechanism of action is postulated to be an alteration in renal hemodynamics, namely increased blood flow and a decrease in the ultrafiltration coefficient, that are the consequence of increased intrarenal prostaglandin production.

Angiotensins↗
PubMed1983

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↗
PubMed1982

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↗
PubMed1980

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↗
PubMed1980

The renin angiotensin system in newborn dogs: developmental patterns and response to acute saline loading.

Plasma renin (PRC) and aldosterone concentrations are known to be high during early postnatal life. Whether this is related to the low rates of renal blood flow or to sodium homeostasis remains unknown. Measurement of PRC, renal blood flow, and its intrarenal distribution were performed in 1- to 3-wk-old puppies subjected to maneuvers known to stimulate or inhibit renin release. In the awake state, PRC was observed to be higher in 2-wk-old puppies than in older or younger dogs, (P less than 0.0001). Significant differences in PRC were also found between litters (P less than 0.0001), but they did not account for the age-related changes. Anesthesia resulted in a 3- to 5-fold rise in PRC, whereas saline expansion suppressed PRC at all ages, the fall tending to become progressively greater with age (P less than 0.09). There was no significant correlation between the age-related changes in PRC and those in renal blood flow or its intrarenal distribution. The results of these experiments demonstrate that in the newborn from a qualitative point of view, PRC changes appropriately in response to various stimuli. However, quantitative age-related differences exist in this regard, reflecting an initial immaturity of the feedback system.

Age Factors↗
PubMed1979

Hemodynamic and excretory response of the neonatal canine kidney to acute volume expansion.

It is generally recognized that developing animals retain sodium due to an enhanced reabsorption in distal tubule segements, even when the amount administered is in excess of their needs. This study was designed to test the relationship between this relative inability to dispose of a saline load and the functional characteristics of the kidney during postnatal maturation. In addition, we explored the role played by some of the factors known to affect natriuresis in the adult subject. Measurements of sodium excretion, glomerular filtration rate (GFR), and renal blood flow (RBF) and its intrarenal distribution were made in three age groups of puppies and in adult dogs. During expansion the GFR rose rapidly and to a similar extent at all ages, but it fell thereafter, the rate of decline being much slower in adult than in developing animals (P less than 0.001). RBF and its intrarenal distribution were not altered by volume expansion. The degree of natriuresis did not reflect either the age-related or the expansion-induced changes in GFR. Fractional and absolute sodium excretion were substantially higher in 2-wk-old puppies than in either 1- or 3-wk-old animals (P less than 0.002). These findings demonstrate that the blunted renal response of the maturing animal to saline loading is due to the persistence of an enhanced tubular reabsorption rather than to a limitation in glomerular filtration.

Animals↗
PubMed1979

Evaluation of infants and children for kidney disease.

An attempt is being made to provide a logical framework for the differential diagnosis of kidney disease in children. The process is facilitated by the fact that the starting points heralding renal disease are rather limited, the great majority of the conditions presenting themselves as one of five signs or five syndromes. Within each of these categories a sequential approach permits passage from the most common diseases and innocuous methods of clinical investigation to more esoteric entities and invasive techniques.

Acute Kidney Injury↗
PubMed1975

Neonatal changes in renal blood flow distribution in puppies.

The intrarenal distribution of blood flow was studied in 31 newborn mongrel puppies from 18 h to 70 days using xenon washout and krypton autoradiography. Mean renal blood flow increased from 0.39 plus or minus 0.05 ml/g per min (SE) the 1st wk to 2.06 plus or minus 0.12 ml/g per min at 6 wk. During the 1st wk of life renal cortex was perfused homo-geneously at 0.88 plus or minus 0.19 ml/g per min (SE) and accounted for 35 plus or minus 4% of the renal blood flow. During the 2nd wk a narrow, rapidly perfused zone of outer cortex was identified which was perfused at 3.35 plus or minus 0.26 ml/g per min, received 19.53 plus or minus 5.05% of the total renal blood flow, and represented 15 plus or minus 4% of the mass of the total cortex. The inner cortex and outer medulla at this time received 53.40 plus or minus 4.12% of the flow at 1.07 plus or minus 0.08 ml/g per min. Outer cortical flow increased with age reaching adult values by about 6-10 wk when the rapidly perfused area represented 40 plus or minus 8% of the cortex. These changes are parallel to the results of previously reported studies with microspheres in newborn puppies and are compatible with the well established maturational changes noted in neonates of several species. They represent the first gas-washout studies in animals during the first 6 wk of life.

Age Factors↗