Modeling Solute Transport and Urine Concentrating Mechanism in the Rat Kidney The goal of this proposal is to use mathematical modeling to investigate aspects of the renal trans- port and dynamics, with an ultimate goal of gaining a better understanding of the mammalian urine concentrating mechanism and solute cycling. Mathematical models of renal tubules and microvessels, coupled with explicit analysis and numerical methods for solving dierential equations, will be used in the following studies: (I) A model of the urine concentrating mechanism of the renal medulla in the rat kidney that represents the relative positions of the tubules and vessels will be developed and used to test the hypothesis: the urine concentrating mechanism of the renal inner medulla of the rat kidney arises from solute mixing in the interstitium, and that mechanism may be comprised of four countercurrent systems, based on the specic 3-dimensional relationships among tubules and vessels. (II) A specic aspect of the 3-dimensional organization in the inner medulla will be considered: interstitial nodal spaces that are bordered by collecting ducts, ascending vasa recta, and ascending thin limbs. A compartment model will be used to test the hypothesis that these microdomains may be essential mixing nodes for targeted delivery and interaction of specic solutes. (III) A dynamic model of the urine concentrating mechanism will be developed and used to track solute (urea, in particular) cycling, to study residence times of solutes, and to study the transient eects of urea loads. The ultimate goal is to gain a better understanding of urea recycling in the renal medulla, and the role of medullary 3-dimensional structure and countercurrent tubular conguration in urea management under physiologic and pathophysiologic conditions. (IV) A slice model of the inner stripe of the rat outer medulla, together with a detailed representation of the epithelial transport processes of the thick ascending limb cell, will be used to study the energy eciency and sodium transport of the thick ascending limbs.

Public Health Relevance

Modeling Solute Transport and Urine Concentrating Mechanism of the Rat Kidney Significance. This proposal aims to provide a more complete and quantitative understanding of the means by which the kidney can produce urine that is more concentrated than blood plasma (i.e., that contains more solute per unit volume than does blood plasma). This basic research is relevant to public health, because abnormalities of the kidney's urine concentrating capability are known to cause, contribute to, be a consequence of, or occur along with, a number of important disorders and diseases, including abnormal body water and salt retention or loss.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK089066-03
Application #
8288902
Study Section
Modeling and Analysis of Biological Systems Study Section (MABS)
Program Officer
Ketchum, Christian J
Project Start
2010-08-09
Project End
2015-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$254,970
Indirect Cost
$90,630
Name
Duke University
Department
Biostatistics & Other Math Sci
Type
Schools of Arts and Sciences
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Leete, Jessica; Gurley, Susan; Layton, Anita (2018) Modeling Sex Differences in the Renin Angiotensin System and the Efficacy of Antihypertensive Therapies. Comput Chem Eng 112:253-264
Sgouralis, Ioannis; Evans, Roger G; Layton, Anita T (2017) Renal medullary and urinary oxygen tension during cardiopulmonary bypass in the rat. Math Med Biol 34:313-333
Jiang, Tao; Li, Yingjie; Layton, Anita T et al. (2017) Generation and phenotypic analysis of mice lacking all urea transporters. Kidney Int 91:338-351
Layton, Anita T; Vallon, Volker; Edwards, Aurélie (2016) A computational model for simulating solute transport and oxygen consumption along the nephrons. Am J Physiol Renal Physiol 311:F1378-F1390
Layton, Anita T; Laghmani, Kamel; Vallon, Volker et al. (2016) Solute transport and oxygen consumption along the nephrons: effects of Na+ transport inhibitors. Am J Physiol Renal Physiol 311:F1217-F1229
Chen, Ying; Fry, Brendan C; Layton, Anita T (2016) Modeling Glucose Metabolism in the Kidney. Bull Math Biol 78:1318-36
Fry, Brendan C; Edwards, Aurélie; Layton, Anita T (2016) Impact of nitric-oxide-mediated vasodilation and oxidative stress on renal medullary oxygenation: a modeling study. Am J Physiol Renal Physiol 310:F237-47
Xie, Luke; Layton, Anita T; Wang, Nian et al. (2016) Dynamic contrast-enhanced quantitative susceptibility mapping with ultrashort echo time MRI for evaluating renal function. Am J Physiol Renal Physiol 310:F174-82
Sgouralis, Ioannis; Layton, Anita T (2016) Conduction of feedback-mediated signal in a computational model of coupled nephrons. Math Med Biol 33:87-106
Sgouralis, Ioannis; Maroulas, Vasileios; Layton, Anita T (2016) Transfer Function Analysis of Dynamic Blood Flow Control in the Rat Kidney. Bull Math Biol 78:923-60

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