EVIDENCE THAT CALGRANULIN IS PRODUCED BY KIDNEY-CELLS AND IS AN INHIBITOR OF CALCIUM-OXALATE CRYSTALLIZATION

Urine produced by normal human kidneys is almost always supersaturated with respect to calcium oxalate (CaOx), the most common constituent o f human kidney stones. Crystallization, with risk of renal damage and kidney stones, appears to be affected by molecules in urine that retar d nucleation, growth, aggregation, and renal cell adherence of CaOx. T he repertoire of such molecules is incompletely known. We have purifie d a 28-kDa protein from urine using salt precipitation, preparative is oelectric focusing, and sizing chromatography. Amino acid composition and NH2-terminal amino sequence analysis showed complete homology to c algranulin. Calgranulin was found to be a potent inhibitor of CaOx cry stal growth (44% of control) and aggregation (50% of control) in the n anomolar range. Calgranulin cDNA was cloned from a human kidney expres sion library Western analysis of human and rat kidney homogenates and mRNA temporal expression from two independent renal epithelial cell li nes showed that calgranulin is produced in the kidney. Given its urina ry abundance and potency, calgranulin may contribute importantly to th e normal urinary inhibition of crystal growth and aggregation and ther efore to the renal defense against clinical stone disease.