The role of zinc in urinary stone disease

In recent years, the role of trace elements in lithogenesis has received steadily increasing attention. It is well documented that some trace elements can influence the morphology and speed of the crystallization process. Zinc has been found in significant amounts in calcium stones relative or organic stones (uric acid and cystine), probably substituting calcium in crystals because of their similarity in charge and size. High Zn levels are present in carbapatite of Randal’s plaques suggesting that zinc could promote calcium phosphate deposition in the medullar interstitium. Large-scale epidemiological studies have found an association of increased dietary zinc intake with increased risk of nephrolithiasis in adults but not in adolescents. Most studies examining urinary zinc levels in adults have reported increased urinary Zn excretion in stone formers. In an experimental model of organic crystal formation produced by silencing xanthine dehydrogenase in Drosophila fly, maneuvers that reduce Zn excretion have shown to reduce crystal formation in the lumen of the Malpighian tubules. This is curious because this is not a model of calcium stone formation. Finally, zinc supplementation has been associated with increased admissions for urinary lithiasis in men, but no change in calcium stone formation in children. Perhaps, some of these contradicting findings can be explained in part by the in vitro effect of zinc on the type and amount of calcium phosphate formed: At low concentrations, Zn inhibited the crystal growth of dicalcium phosphate dihydrate, octacalcium phosphate, and apatite, and at higher concentrations, it promoted the formation of amorphous calcium phosphate. Thus, further studies are needed to see whether manipulation of Zn metabolism can inhibit calcium stone formation.