New insights into the pathogenesis of idiopathic hypercalciuria

Idiopathic hypercalciuria (IH) is the most common metabolic abnormality in patients with calcium kidney stones. It is characterized by normocalcemia, absence of diseases that cause increased urine calcium, and calcium excretion that is greater than 250 mg/d in women and 300 mg/d in men. Subjects with IH 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 seen commonly in balance studies, especially on a low-calcium diet. The mediator of decreased renal calcium reabsorption is not clear; it is not associated with either an increase in filtered load of calcium or altered parathyroid hormone levels. There is an increased incidence of hypercalciuria in first-degree relatives of those with IH, but IH 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 the manifestations of IH in at least some patients.