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Biomedical subjects

D I Goldsmith

Publications and source records attributed to D I Goldsmith.

8 recordsLinked to original sources

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

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

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

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

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

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