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
Edwards, Aurélie; Castrop, Hayo; Laghmani, Kamel et al. (2014) Effects of NKCC2 isoform regulation on NaCl transport in thick ascending limb and macula densa: a modeling study. Am J Physiol Renal Physiol 307:F137-46
Sgouralis, Ioannis; Layton, Anita T (2014) Theoretical assessment of renal autoregulatory mechanisms. Am J Physiol Renal Physiol 306:F1357-71
Fry, Brendan C; Edwards, Aurélie; Sgouralis, Ioannis et al. (2014) Impact of renal medullary three-dimensional architecture on oxygen transport. Am J Physiol Renal Physiol 307:F263-72
Fry, Brendan C; Layton, Anita T (2014) Oxygen transport in a cross section of the rat inner medulla: impact of heterogeneous distribution of nephrons and vessels. Math Biosci 258:68-76
Edwards, Aurelie; Layton, Anita T (2014) Calcium dynamics underlying the myogenic response of the renal afferent arteriole. Am J Physiol Renal Physiol 306:F34-48
Ryu, Hwayeon; Layton, Anita T (2014) Tubular fluid flow and distal NaCl delivery mediated by tubuloglomerular feedback in the rat kidney. J Math Biol 68:1023-49
Pannabecker, Thomas L; Layton, Anita T (2014) Targeted delivery of solutes and oxygen in the renal medulla: role of microvessel architecture. Am J Physiol Renal Physiol 307:F649-55
Moss, Robert; Layton, Anita T (2014) Dominant factors that govern pressure natriuresis in diuresis and antidiuresis: a mathematical model. Am J Physiol Renal Physiol 306:F952-69
Nieves-Gonzalez, Aniel; Clausen, Chris; Layton, Anita T et al. (2013) Transport efficiency and workload distribution in a mathematical model of the thick ascending limb. Am J Physiol Renal Physiol 304:F653-64
Layton, Anita T; Bankir, Lise (2013) Impacts of Active Urea Secretion into Pars Recta on Urine Concentration and Urea Excretion Rate. Physiol Rep 1:

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