(366a) Determinants of Calcium Reabsorption in the Rat Kidney

We have developed a mathematical model of calcium (Ca²⁺) transport along key segments of the rat nephron to investigate the factors that promote hypercalciuria (i.e., abnormally high levels of calcium in the urine), one of the leading causes of kidney stone formation. The reabsorption of Ca²⁺ occurs passively in the thick ascending limb, and its urinary excretion is finely adjusted downstream, in the distal convoluted (DCT) and connecting (CNT) tubules.  Our model represents the detailed epithelial transport of Ca²⁺ and other solutes in these segments; it accounts for the specific apical and basolateral transporters of each cell type. Solute concentrations, volume, pH, and electric potential in the tubular lumen and the epithelial cells are determined, as a function of position along the tubule, by solving steady-state conservation equations coupled to flux expressions. Model simulations reproduce experimentally observed variations in cellular Ca²⁺ uptake as a function of extracellular pH and Na⁺ concentrations. The model predicts complex interactions between the reabsorption of Ca²⁺ and that of other solutes in the nephron; in particular, urinary Ca²⁺ excretion appears to be strongly modulated by the transport of NaCl. Our results also suggest that the DCT and CNT can adapt to upstream variations in Ca²⁺ transport, but not always sufficiently to prevent hypercalciuria.