Hypercalciuria revisited: one or many conditions?

Idiopathic hypercalciuria is a defect occurring in 5-10% of the general population and most commonly detected in patients with calcium kidney stones or osteoporosis. Although high-penetrance autosomal dominant inheritance cannot be ruled out, hypercalciuria is probably a polygenic phenomenon. Findings obtained in monogenic disorders characterized by renal calcium stones, and/or hypercalciuria, and/or nephrocalcinosis, have suggested a number of genes as candidate genes in the pathogenesis of idiopathic hypercalciuria, i.e. soluble adenylate cyclase, calcium sensing receptor, vitamin D receptor and 1-alpha hydroxylase, sodium-phosphate co-transporter-2, claudin-16, chloride channel 5, etc. All the genetic findings obtained so far do not support the idea of different types of idiopathic hypercalciuria, i.e. absorptive, renal, and resorptive. On the contrary, they support clinical observations, which suggest idiopathic hypercalciuria as a single disorder characterized by altered calcium transport in the intestine, kidney and bone, due to various different combinations of multiple genetic and dietary players.