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  • 1
    ISSN: 1432-198X
    Keywords: Phosphate transport ; Development ; Mineral metabolism ; Growth hormone ; Insulin-like growth factor-1 ; Phosphodiesters ; Nuclear magnetic resonance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Direct correlations have been observed between the renal intracellular concentration of phosphate ([Pi]i) and postnatal age (3–13 weeks in rats, 1–4 weeks in guinea pigs), as well as between the dietary supply of Pi and [Pi]i. In turn, [Pi]i was found to be inversely correlated with the renal tubular transport of phosphate (TRPi). However, age- and diet-related differences in [Pi]i alone do not explain the high capacity of Na+-Pi cotransport present in the kidney of the neonate. Therefore, we explored whether changes in TRPi induced by altering Pi demand (whole body growth or bone mineralization) are mediated by factors other than changes in [Pi]i. TRPi was measured in vivo and nuclear magnetic resonance-visible [Pi]i in perfused kidneys of 8-week-old genetically growth hormone (GH)-deficient and GH-treated dwarf rats and in 8-week-old thyroparathyroidectomized (TPTX) Sprague-Dawley (SD) rats treated or untreated with etidronate (EHDP), an inhibitor of bone mineralization. In dwarf rats, [Pi]i was 1.2±0.2 mM and TRPi 2.4±0.2 μmol/ml glomerular filtrate. In TPTX SD rats, [Pi]i was 1.6±0.2 mM and TRPi 4.2±0.3 μmol/ml glomerular filtrate. Administration of GH to dwarf rats resulted in increases in Pi transport of 38%±8% (P〈0.05), while administration of EHDP to TPTX SD rats decreased TRPi by 52%±7% (P〈0.05). Neither GH nor EHDP significantly affected [Pi]i. Thus, in the rat changes in TRPi due to alterations in Pi demand occur in the absence of significant changes in [Pi]i. Consequently at least two complementary but independent regnlatory factors, GH and low [Pi]i, account for the high rates of TRPi observed in the neonate.
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  • 2
    ISSN: 1432-198X
    Keywords: Kidney ; Development ; Tubular ; Energy ; Glycolysis ; Sodium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The proximal tubules of newborn and adult animals reabsorb a similar fraction of the filtered load of Na+ and H2O (65%–70%). In tubules from adult animals, transcellular, active Na+ reabsorption accounts for one-third of the total, while two-thirds occur passively through the paracellular pathway, driven by hydrostatic and oncotic forces (one-third) and by cell-generated effective osmotic and ionic gradients (one-third). Since two-thirds of the Na+ is reabsorbed passively and does not require energy, the mature proximal tubule has a high Na+/O2 molar ratio (48 Eq of Na+/mol of O2). Measurements of ouabain-sensitive oxygen consumption in suspensions of proximal tubules indicate that in newborn, aerobic metabolism can support about 50% of the net Na+ transport rate compared with the 33% in tubules from adult animals. Independent confirmation of the direct and proportional relationship between active Na+ transport and ouabain-sensitive O2 consumption exists for the adult but not for the newborn. However, measurements of epithelial conductances and of transepithelial hydrostatic and oncotic pressure differences indicate that passive paracellular fluxes can account for the remaining 50% of the proximal Na+ reabsorption in newborn. The high permeability of the proximal tubules of newborn animals to small molecular weight solutes suggests that cell-generated osmotic and ionic transepithelial gradients are minimal in the tubules of newborn animals. Yet in the newborn, the osmolality of the end proximal tubule fluid was found to exceed that in plasma. This indicates that osmotic gradients due to differences in reflection coefficients for preferentially reabsorbed solutes and Cl− do exist across the proximal tubules of the newborn and suggests that these gradients may contribute to Na+ and H2O reabsorption. If this is indeed the case, then the contribution of active and of hydrostatic and oncotic pressure-driven flows to the overall reabsorption of Na+ and fluid has been overestimated. Resolution of this discrepancy requires measurements of the reflection coefficients for HCO 3 − and Cl− in the proximal tubule of the newborn. The metabolic processes by which energy is supplied to renal proximal cells during development are also incompletely characterized. There is evidence that maturation of aerobic metabolism, Krebs cycle enzymes activity, and of the mitochondrial membrane surface area precede the development of net reabsorptive transport (Na+, H2O, HCO3, glucose). By contrast, maturation of Na+−K+-ATPase activity at the basolateral cell membrane follows that in reabsorptive transport and does not limit its development. The extent to which age-related changes in reabsorptive fluxes are due to the development of luminal membrane transport systems, to the decrease in paracellular permeability, or both remains to be determined. The high activity of enzymes in the hexosemonophosphate pathway and the high NADH/NAD ratio present during the first few weeks of extrauterine life poise the proximal tubules for high rates of biosynthesis of membrane lipids, glycoproteins, nucleic acids, and transporter proteins necessary for final differentiation.
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  • 3
    ISSN: 1432-198X
    Keywords: Phosphate ; Proximal tubule ; Development ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies performed in our laboratory on the isolated perfused kidney of the guinea pig have demonstrated that the rate of Pi reabsorption is substantially greater in the newborn than in the adult, when appropriate corrections are being made either for differences in glomerular filtration rate (GFR) or in renal tubular mass. In order to determine the location of this enhanced reabsorption along the nephron, micropuncture experiments were performed on euvolemic, non-fasted guinea pigs 5–14 and 42–49 days of age, maintained on standard guinea-pig chow diet (0.76% Pi). Concomitant measurements of overall kidney function were also obtained. The results confirmed that fractional reabsorption of Pi (TRPi%) across the entire kidney was significantly higher (P〈0.01) in the newborn (89.93±2.55%) than in the adult (78.25±2.89%) animals. The difference was also significant (P〈0.05) when TRPi was expressed in mol/ml GFR (1.87±0.14 vs 1.53±0.12, respectively). At comparable locations along the proximal tubule (TF/Pin of 1.90±0.16 in the newborn, and 1.79±0.15 in the adult,P〉0.70), the fraction of the filtered load of Pi reabsorbed was significantly higher (P〈0.001) in the immature (76.66±2.74%) than in the mature (67.21±2.74%) guinea pigs. Estimates based on the differences between proximal Pi reabsorption and the urinary excretion of Pi indicate that the reabsorption of Pi in tubular segments located beyond the proximal tubule is also enhanced in the newborn when compared with the adult (15.62±2.11% vs 10.51±1.83%, respectively,P〈0.05). Alternatively, this finding may be interpreted to represent a higher fractional reabsorption of Pi by deep nephrons.
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