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Mathematical modelling of the proximal portion of the nephron
Author(s) -
Terkildsen Jonna,
Nickerson David,
Hamilton Kirk,
Hunter Peter
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1129.5
Subject(s) - nephron , computer science , medicine , kidney
We have developed mathematical models of the glomerulus, proximal tubule and peritubular capillaries, building upon the work pioneered by Alan Weinstein ( AJP 258 :F612, 1990; AJP 292 :F1164, 2007 ). The cell and tubule framework defining the proximal tubule model was expanded to include detailed mechanistic models of the key ion and solute transporters. These transporter models explicitly characterise individual steps in the transport cycle, and thus enable the simulation of the effects of inhibitors and/or drugs on protein function. The follow‐on effects of these modifications, on whole‐cell and tubular transport, can then be predicted. We demonstrate this functionality through an analysis of glucose transport in the proximal tubule following the inhibition of SGLT2 by dapagliflozin. The behaviour of the proximal portion of the nephron, however, depends on the dynamics of not only the proximal tubular cells, but also the uptake of solutes into the blood. The integration of the capillary models with the proximal tubule model enables the investigation of the importance of feedback between the proximal tubule and the capillaries on the functionality of the proximal portion of the nephron as a whole.