A Model of Calcium Transport along the Rat Nephron

Abstract

We developed a mathematical model of calcium (Ca2+) transport along the rat nephron to investigate the factors that promote hypercalciuria. The model is an extension of the flat medullary model of Hervy and Thomas (Am J Physiol Renal Physiol 284: 65, 2003). It explicitly represents all the segments beyond the proximal tubule, and distinguishes between short‐ and long‐looped nephrons. It solves dynamic conservation equations to determine NaCl, urea, and Ca2+ concentration profiles in tubules, vasa recta, and interstitium. Calcium is known to be reabsorbed passively in the thick ascending limb, and actively in the distal convoluted (DCT) and connecting (CNT) tubules. Our simulations suggest that urinary Ca2+ excretion is strongly modulated by water and NaCl reabsorption along the nephron. Our model also predicts that the passive diffusion of Ca2+ from the loop of Henle generates a significant cortico‐medullary interstitial Ca2+ concentration gradient. Finally, our results suggest that the DCT and CNT can adapt to upstream variations in Ca2+ transport, but not always sufficiently to prevent hypercalciuria. This work was supported by the program EMERGENCE (EME 0918) of Université Paris 6.