The proximal tubule reabsorbs 80% of the filtered bicarbonate in adult animals. The transporters responsible for apical proton secretion and basolateral bicarbonate transport have been characterized and are limited to their respective membranes for efficient vectorial bicarbonate transport. Acid-base changes can affect the rate of proximal tubule bicarbonate absorption, and chronic changes can produce an intrinsic adaptation in transporter activity. However, little is known about the mechanisms of acidification, the rate of transporter activity and the regulation of acidification in the developing proximal tubule. Nephrogenesis is still occurring in newborn infants born before 36 weeks gestation. These infants often develop metabolic and respiratory acidosis. It is known that immature proximal tubules transport fluid and bicarbonate at a fraction of the adult rate. However, it is unknown whether immature proximal tubules are functioning at maximal capacity or if an adaptive augmentation in transport is possible. The ability of the kidney to adapt to acute and chronic acid-base changes affects the ability of the organism to respond to and survive these environmental stresses. With the increased survivorship of very premature infants, the ability of the kidney to adapt to metabolic and respiratory acidosis is of great clinical importance.
The first aim of this proposal is to use in vitro microperfusion and measurements of intracellular pH to examine how differentiation of the proximal tubule from the primitive renal vesicle to the mature tubular segment affects the localization and activity of transporters responsible for acidification.
The second aim i s to examine if acute changes in peritubular pH, pCO2 and HCO3 as well as changes in peritubular physical factors in vitro can modulate acidification in the immature proximal tubule. Finally, I will examine if the intrinsic rate of development and maturation of proximal tubular acidification can be altered by imposing environmental stresses on newborn rabbits which frequently affect premature infants.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK041612-04
Application #
2141834
Study Section
General Medicine B Study Section (GMB)
Project Start
1991-02-01
Project End
1996-01-31
Budget Start
1994-02-01
Budget End
1995-01-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Baum, Michel (2016) Luminal angiotensin II stimulates rat medullary thick ascending limb chloride transport in the presence of basolateral norepinephrine. Am J Physiol Renal Physiol 310:F294-9
Baum, Michel (2016) Neonatal nephrology. Curr Opin Pediatr 28:170-2
Baum, Michel (2015) Overview of polycystic kidney disease in children. Curr Opin Pediatr 27:184-5
Lozano, German; Elmaghrabi, Ayah; Salley, Jordan et al. (2015) Effect of prenatal programming and postnatal rearing on glomerular filtration rate in adult rats. Am J Physiol Renal Physiol 308:F411-9
Babich, Victor; Vadnagara, Komal; Di Sole, Francesca (2015) Dual Effect of Adenosine A1 Receptor Activation on Renal O2 Consumption. J Cell Physiol 230:3093-104
Gleason, Catherine E; Frindt, Gustavo; Cheng, Chih-Jen et al. (2015) mTORC2 regulates renal tubule sodium uptake by promoting ENaC activity. J Clin Invest 125:117-28
Gattineni, Jyothsna; Baum, Michel (2015) Developmental changes in renal tubular transport-an overview. Pediatr Nephrol 30:2085-98
Cheng, Chih-Jen; Yoon, Joonho; Baum, Michel et al. (2015) STE20/SPS1-related proline/alanine-rich kinase (SPAK) is critical for sodium reabsorption in isolated, perfused thick ascending limb. Am J Physiol Renal Physiol 308:F437-43
Pirojsakul, Kwanchai; Gattineni, Jyothsna; Dwarakanath, Vangipuram et al. (2015) Renal NHE expression and activity in neonatal NHE3- and NHE8-null mice. Am J Physiol Renal Physiol 308:F31-8
Mansuri, Asifhusen; Elmaghrabi, Ayah; Legan, Susan K et al. (2015) Transient Exposure of Enalapril Normalizes Prenatal Programming of Hypertension and Urinary Angiotensinogen Excretion. PLoS One 10:e0146183

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