Downloadable Tool for Modeling of Salt, Urea and Water Transport in a Renal Tubule Segment: Application to the DCT.

Abstract

We have devised a user-friendly downloadable, standalone application that solves a set of ordinary differential equations describing steady-state mass balance for salt (NaCl), urea and water in a single renal tubule with axial flow. The model was programmed in Python using an explicit ordinary differential equation solver. The standalone version allows users to interact with a GUI to insert parameter values and initiate the calculations. It outputs volume flow rate and solute concentrations as a function of position along the tubule. We illustrate the use of the model to address questions about the roles of the mammalian distal convoluted tubule (DCT) in water balance. The simulations suggest an important role for the DCT as a second diluting segment beyond the cortical thick ascending limb (CTAL), consistent with a critical function in excretion of water loads. Simulation of the effect of thiazide diuretics, which inhibit active salt absorption in the DCT, provides an explanation for the observation that these agents can produce hyponatremia when used clinically. The simulations also indicate that the DCT may transport salt in either direction (in accord with micropuncture findings), depending on the salt concentration in the fluid entering from the CTAL. Salt reabsorption by active transport is balanced by passive salt secretion as the luminal salt concentration approaches an asymptotic 'static head' level. The tool will allow users with no mathematical modeling experience to simulate transport in renal tubules, working toward the goal of expanding the use of mathematical modeling in physiology.