Three-dimensional anatomy and renal concentrating mechanism. II. Sensitivity results.

A mathematical model has been developed to simulate hypertonic urine formation in the renal medulla. The model uses published values of membrane transport parameters, as have other models, but is unique in its representation of the three-dimensional anatomy of the medulla. The model successfully predicts measured fluid flows, osmolarities, and NaCl and urea concentrations. The model results are presented in the companion to this paper [A. S. Wexler, R. E. Kalaba, D. J. Marsh. Am. J. Physiol. 260 (Renal Fluid Electrolyte Physiol. 29): F368-F383, 1991.]. In this paper we provide tests of the sensitivity of model performance to variations in the description of the anatomy and in membrane transport parameters. From these studies we conclude that 1) strict counterflow arrangements are required in the outer stripe to prevent loss of NaCl to the systemic circulation, 2) the radial organization in the inner stripe materially improves performance of the inner medulla, 3) radial organization of the inner medulla is essential to hypertonic urine formation there, 4) the model is most sensitive to variation in collecting duct parameters, and 5) reabsorption of urea in the distal tubule improves system performance. The results support the claim that the three-dimensional structure, as captured in the model, provides a crucial framework for the production of hypertonic urine.