Genetics of hypercalciuria and kidney stones

Kidney stone disease is common and causes considerable morbidity. The pathogenesis of kidney stone disease is incompletely understood; however, it is well known that hypercalciuria is associated with kidney stone formation and that urinary calcium concentration plays a significant role in the overall urinary lithogenic profile, which is also influenced by urinary volume, urinary pH, and the concentration of minerals and metabolites, including phosphate, oxalate, and citrate. Kidney stone disease and hypercalciuria are heritable; in this chapter, we review the progress that has been made in understanding the genetic basis of these traits via monogenic and polygenic studies in humans and animal models. These studies have revealed the importance of renal transporters and channels, ions, protons, amino acids, vitamin D metabolic pathways, the calcium-sensing receptor signaling pathway, bicarbonate-sensing, oxalate, cysteine, uric acid, purines, and adiposity in mineral metabolism and kidney stone formation.