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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Modeling and Analysis of Biological Systems Study Section (MABS)
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Ketchum, Christian J
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Duke University
Biostatistics & Other Math Sci
Schools of Arts and Sciences
United States
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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
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
Liu, Runjing; Layton, Anita T (2016) Modeling the effects of positive and negative feedback in kidney blood flow control. Math Biosci 276:8-18
Chen, Ying; Fry, Brendan C; Layton, Anita T (2016) Modeling Glucose Metabolism in the Kidney. Bull Math Biol 78:1318-36
Layton, Anita T (2015) Recent advances in renal hemodynamics: insights from bench experiments and computer simulations. Am J Physiol Renal Physiol 308:F951-5
Fry, Brendan C; Edwards, Aurélie; Layton, Anita T (2015) Impacts of nitric oxide and superoxide on renal medullary oxygen transport and urine concentration. Am J Physiol Renal Physiol 308:F967-80
Layton, Anita T; Edwards, Aurélie (2015) Predicted effects of nitric oxide and superoxide on the vasoactivity of the afferent arteriole. Am J Physiol Renal Physiol 309:F708-19
Layton, Anita T; Vallon, Volker; Edwards, Aurélie (2015) Modeling oxygen consumption in the proximal tubule: effects of NHE and SGLT2 inhibition. Am J Physiol Renal Physiol 308:F1343-57

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