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.