What is the pathophysiology of hypercalciuria?

Updated: Jun 02, 2021
  • Author: Stephen W Leslie, MD, FACS; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Urinary excretion of calcium is the result of the complex interplay of the gastrointestinal tract, the kidney, and bone and is regulated by multiple hormones. Hypercalciuria is believed to be a polygenic trait and is significantly influenced by diet.

Idiopathic hypercalciuria is the most common metabolic abnormality in patients with calcium kidney stones. Subjects with idiopathic hypercalciuria have a generalized increase in calcium turnover, which includes increased gut calcium absorption, decreased renal calcium reabsorption, and a tendency to lose calcium from bone. Despite the increase in intestinal calcium absorption, a negative calcium balance is commonly seen in balance studies, especially in patients on a low-calcium diet. The mediator of decreased renal calcium reabsorption is unclear; it is not associated with either an increase in filtered renal calcium or altered parathyroid hormone (PTH) levels.

An increased incidence of hypercalciuria is observed in first-degree relatives of individuals with idiopathic hypercalciuria, but it appears to be a complex polygenic trait with a large contribution from diet to expression of increased calcium excretion.

Increased tissue vitamin D response may be responsible for manifestations of idiopathic hypercalciuria in at least some patients. [11, 12] Moreover, deficiency in the enzyme that inactivates 1,25(OH)2D, 1,25(OH)2D-24 hydroxylase causes elevated vitamin D, hypercalciuria, nephrocalcinosis, and kidney stones. [13] Furthermore, dysregulation of the calcium-sensing receptor ̶ Claudin-14 axis likely contributes to the development of hypercalciuria. [14, 15, 16]

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