Nephrolithiasis

Genetic factors are important determinants for kidney stone formation. Cystinuria, primary hyperoxaluria, and X-linked nephrolithiasis (Dent's disease) are monogenic kidney stone diseases for which responsible genes have been identified. Familial stone disease with hyperuricosuria or renal tubular acidosis has been described in several clinical settings. Idiopathic hypercalciuria is the most common stone risk factor, and evidence in humans and in a rat model indicates that hypercalciuria is a complex, polygenic trait. Some candidate genes for idiopathic hypercalciuria are suggested by the known physiology, including those encoding the vitamin D receptor, the 1 alpha-hydroxylase of vitamin D, the calcium-sensing receptor, the renal sodium-dependent phosphate transporter, and chloride channels, but others remain to be identified. The multifaceted physiology of hypercalciuria may reflect the combined effects of polymorphisms in several genes.