A computational model of epithelial solute and water transport along a human nephron.

Published

Journal Article

We have developed the first computational model of solute and water transport from Bowman space to the papillary tip of the nephron of a human kidney. The nephron is represented as a tubule lined by a layer of epithelial cells, with apical and basolateral transporters that vary according to cell type. The model is formulated for steady state, and consists of a large system of coupled ordinary differential equations and algebraic equations. Model solution describes luminal fluid flow, hydrostatic pressure, luminal fluid solute concentrations, cytosolic solute concentrations, epithelial membrane potential, and transcellular and paracellular fluxes. We found that if we assume that the transporter density and permeabilities are taken to be the same between the human and rat nephrons (with the exception of a glucose transporter along the proximal tubule and the H+-pump along the collecting duct), the model yields segmental deliveries and urinary excretion of volume and key solutes that are consistent with human data. The model predicted that the human nephron exhibits glomerulotubular balance, such that proximal tubular Na+ reabsorption varies proportionally to the single-nephron glomerular filtration rate. To simulate the action of a novel diabetic treatment, we inhibited the Na+-glucose cotransporter 2 (SGLT2) along the proximal convoluted tubule. Simulation results predicted that the segment's Na+ reabsorption decreased significantly, resulting in natriuresis and osmotic diuresis.

Full Text

Duke Authors

Cited Authors

  • Layton, AT; Layton, HE

Published Date

  • February 25, 2019

Published In

Volume / Issue

  • 15 / 2

Start / End Page

  • e1006108 -

PubMed ID

  • 30802242

Pubmed Central ID

  • 30802242

Electronic International Standard Serial Number (EISSN)

  • 1553-7358

International Standard Serial Number (ISSN)

  • 1553-734X

Digital Object Identifier (DOI)

  • 10.1371/journal.pcbi.1006108

Language

  • eng