Renal tubular calcium transport, physiology and clinical significance: terra «cognita»

The kidneys are the only place of the absorpted calcium elimination. About 10 g of elemental calcium passes through a glomerular filter per day, while the daily urinary calcium excretion is only 100-200 mg. 99% of the filtered calcium undergoes reabsorption in various parts of the nephron. Dysregulation of the renal calcium handling leads to adverse renal manifestations such as hypercalciuria, nephrolithiasis, nephrocalcinosis, kidney tubular injury, chronic kidney disease. Hypercalciuria is associated with the dysfunction of various molecular regulatory mechanisms responsible for calcium transport in the nephron. The paracellular calcium transport in the proximal tubules and in the thick ascending limb (TAL) of the Henle’s loop is mediated by claudins, a group of membrane proteins of epithelial cell tight junctions. Claudins form cation-selective channels with high permeability to calcium. Deletions of, or mutations in genes encoding renal claudins can cause genetic diseases characterized by hypercalciuria. The main regulator of the paracellular transport of calcium in the TAL is calcium-sensitive receptors (CaSR) of the basolateral membrane of epithelial cells. Various mutations and polymorphisms of CASR gene are associated with hypercalciuria, nephrolithiasis and nephrocalcinosis. In the distal tubules luminal calcium transfer into the cell occurs via specific selective calcium TRPV5 (transient receptor potential channel, vanilloid subgroup) channels, which play a key role in calcium reabsorption. Parathyroid hormone (PTH) is the principle hormone that has been described to regulate the abudance and activity of TRPV5 channels of the distal tubules’ epithelial cells. Moreover, αKloto protein and fibroblast growth factor 23 (FGF23) are involved in the regulation of renal tubule calcium transport in this site of the nephron. Although over the past years major advances have been made in the understanding of the renal calcium transport physiology and its hormonal regulation, at present therapeutic options aiming to reduce hypercalciuria remain restricted. Further effort is necessary for the development of targeted therapy based on the underlying pathophysiological mechanisms of nephrolithiasis.

кальций, гиперкальциурия, нефролитиаз, паратиреоидный гормон, клаудины, селективные кальциевые TRPV5 каналы, кальций-чувствительные рецепторы, calcium, hypercalciuria, nephrolithiasis, parathyroid hormone, claudins, transient receptor potential vanilloid 5 channels, calcium sensing receptors

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