Genetic Hypercalciuria: A Major Risk Factor in Kidney Stones

Kidney stones are prevalent, cause considerable morbidity though little mortality. The most common metabolic abnormality in patients with kidney stones is hypercalciuria, which is a complex metabolic trait that is dependent on three major organs: the amount of dietary calcium absorbed, any net calcium released from bone resorption in excess of formation, and the extent to which filtered calcium is reabsorbed in the renal tubule. Each of these calcium fluxes is under control of number of factors and hormones, including parathyroid hormone and 1,25-dihydroxy-vitamin D. Whether a patient forms a kidney stone is dependent not only on the magnitude of the hypercalciuria but also on urinary volume, excretion of other ions, including oxalate, citrate, and phosphate, and on local factors in the urinary tract. Hypercalciuria, and resultant stone formation, is a partially inherited trait. Given the many determinants of not only urine calcium excretion, but also the other factors that determine whether a patient will form a kidney stone, it is clear that multiple genetic loci are involved. In this chapter, we will describe the progress made in understanding the genetic basis for hypercalciuria and stone formation in both experimental models and in man.