NEONATAL PROXIMAL TUBULAR ACIDIFICATION

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Glucocorticoids are often administered to pregnant women to accelerate lung maturation and prevent respiratory distress syndrome. The effect of glucocorticoids on the developing kidney is unknown. The first aim of this proposal is to examine whether prenatal glucocorticoids affect nephrogenesis in fetal rabbits. Glucocorticoids have also been shown to play a role in the maturation of several organs. We plan to examine if the postnatal increase in glucocorticoid levels are responsible for the maturational increase in proximal tubule acidification and decrease in proximal tubule phosphate transport. Premature neonates have marked urinary losses of NaCl and are in negative salt balance causing dehydration and hyponatremia. The majority of NaCl transport in adult animals is by the proximal tubule. However, the mechanism of proximal tubule NaCl transport by the premature and term neonate is unknown. The second aim of this proposal is to use in vitro microperfusion to examine the mechanism and regulation of NaCl transport and factors which may play a role in maturation of NaCl transport with renal development. The final aim of this proposal focuses on the signal transduction system in neonatal proximal tubule. Several hormones which regulate adult proximal tubule transport have a blunted or no response in the neonatal proximal tubule. The reason, for this block in signal transduction is unknown. We will examine why the response to PTH and dopamine are attenuated in the neonate and if glucocorticoids affect the maturation of signal transduction.