Pathogenesis of primary hypercalciuria

Hypercalciuria may be classified into absorptive, renal and re- sorptive forms, depending on whether the primary defect is in- testinal hyperabsorption of calcium, renal leak of calcium, or excessive bone resorption. In absorptive hypercalciuria, the pathogenetic role of vitamin D is uncertain, and mutations in the chloride channel may occur mainly in association with Dent’s disease. Early studies suggest that a new soluble adenylyl cyclase ( A H R A C ) may be etiologically important in this condition, since base changes in this gene occur much more frequently and are directly correlated with intestinal cal-cium absorption. The distal nephron is the site of reabsorption of the final 20% of filtered calcium. The transcellular reabsorption of calcium begins with a passive entry of Ca 2 + through apical calcium channels, followed by diffusion through cytosol and active ex- trusion across the basolateral membrane. Calcium transport in the nephron is regulated by luminal pH, calcitriol, estrogen, parathyroid hormone, rostaglandin E 2 , and sodium load. A biochemical picture of renal hypercalciuria may be produced by acid load from dietary animal proteins, prostaglandin E 2 ex- cess, sodium load, hypoparathyroidism, and estrogen defi- ciency. So far, mutations in apical calcium channel have not been found. The hallmark of resorptive hypercalciuria is primary hyper-parathyroidism. Bone loss often accompanies bsorptive hy- percalciuria. A H R A C may be implicated, since base changes in this gene are inversely correlated with spinal bone density. Dietary acid load from high nimal protein diet may cause hy- percalciuria, in part by stimulating bone loss