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Exploration of pressure‐natriuresis mechanisms using a lumped, two‐nephron whole‐kidney model

We present a two‐nephron whole‐kidney model of salt and water balance, which represents the short and long nephron populations and the associated cortical and medullary vasculature. The aim is to provide a context with sufficient complexity to explore and compare proposed mechanisms and features of pressure‐natriuresis, including: (1) the effects of blood pressure (BP) on proximal tubule sodium transport; (2) the sensitivity of medullary blood flow (MBF) to renal perfusion pressure and consequences for natriuresis and diuresis; (3) perturbations of TGF and myogenic effects on glomerular filtration rate (GFR). Without addressing detailed kinetic transport mechanisms in different cell‐types along each nephron segment, the model nonetheless contains sufficient detail of segment‐specific transport to serve as a basis for simulating the effects of the principal regulators of renal function (hormones, local paracrine effects, sympathetic nerve activity). The model can be adapted to different species (total number of nephrons, relative numbers and lengths of short and long nephrons, etc.), and will be used to replace the simpler kidney module of the classic Guyton model of blood pressure regulation. The model will be provided as an open source program with a flexible user interface for visualization and exploration of user‐defined scenarios.