A model of calcium transport along the rat nephron
Résumé
We developed a mathematical model of calcium ($Ca^{2+}$) 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: F65-F81, 2003). It explicitly represents all the segments beyond the proximal tubule, and distinguishes between superficial and deep nephrons. It solves dynamic conservation equations to determine NaCl, urea, and $Ca^{2+}$ 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 $Ca^{2+}$ molar flow and concentration profiles differ significantly between superficial and deep nephrons, such that the latter deliver less $Ca^{2+}$ to the collecting duct. In the base case, the urinary $Ca^{2+}$ concentration and fractional excretion are predicted as 2 mM and $0.5 \%$, respectively. We also found that urinary $Ca^{2+}$ excretion is strongly modulated by water and NaCl reabsorption along the nephron. In addition, our model predicts that the passive diffusion of $Ca^{2+}$ from the loop of Henle generates a significant axial $Ca^{2+}$ concentration gradient in the medullary interstitium. Finally, our results suggest that the DCT and CNT can adapt to upstream variations in $Ca^{2+}$ transport, but not always sufficiently to prevent hypercalciuria.