Role of nephrocalcin in inhibition of calcium oxalate crystallization and nephrolithiasis.

Kidney cells produce at least three proteins that slow the rate of calcium oxalate crystallization. Nephrocalcin (NC), one of the three, is an acidic glycoprotein that contains gamma-carboxyglutamic acid (GLA), and inhibits nucleation, aggregation and growth of calcium oxalate crystals. Nephrocalcin is abnormal in urine of stone-forming patients, in lacking GLA. It acts by absorbing to crystal surfaces. NC is produced by cultured renal proximal tubule cells, and by some lines of renal carcinoma cells, but its regulation is not yet characterized. Its sequence is not known, nor do we known the molecular basis for the abnormal character of NC is stone-forming patients. Compared to Tamm-Horsefall protein and uropontin, the two other inhibitors, NC is very potent, and is probably of major importance in protecting kidneys against supersaturations caused by normal water conservation.