Inhibitors within the nephron.

Kidney-derived inhibitors of crystal growth and aggregation prevent supersaturations created by water conservation from expressing themselves in pathological soft tissue calcifications and intranephronal crystallizations. These inhibitors include nephrocalcin (NC), an acidic glycoprotein produced in proximal tubules and thick ascending limbs of Henle's loop, and the Tamm-Horsfall glycoprotein (THP), produced only in the thick ascending limb. NC inhibits growth and aggregation of calcium oxalate monohydrate (COM), the major crystalline component of human renal stones, THP inhibits only COM aggregation. Patients who form COM stones produce abnormal NC molecules that lack gamma-carboxyglutamic acid and fail to inhibit COM crystallizations normally.