What is the pathophysiology of hypercalciuria?

Updated: Apr 23, 2019
  • Author: Stephen W Leslie, MD, FACS; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Answer

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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