Abstract
We have developed a mathematical model of calcium (Ca2+) transport from the thick ascending limb to the inner medullary collecting duct (IMCD) to investigate the factors that promote hypercalciuria, one of the main risk factors for kidney stone formation. Calcium is reabsorbed passively in the thick ascending limb, and actively in the distal convoluted (DCT) and connecting (CNT) tubules. The 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. Model simulations reproduce experimentally observed variations in urinary Ca2+ excretion following treatment by furosemide or Ca2+ transporter inhibition. The model predicts complex interactions between the reabsorption of Ca2+ and that of other solutes in the nephron. Our results also suggest that the DCT and CNT barely adapt to upstream variations in Ca2+ transport. In contrast, regulation of the IMCD water permeability by calcium sensing mechanisms is predicted to significantly mitigate the effects of high Ca2+ loads in the distal nephron.Grant Funding Source: Supported by the Agence Nationale de la Recherche (France)
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