Nephrocalcin in patients with renal cell carcinoma

Nephrocalcin, an acidic glycoprotein that inhibits calcium oxalate crystal growth, has been previously localized in proximal tubules of kidneys by an immunohistochemical staining method and purified from tissue culture media of 2 renal carcinoma cell lines. A polyclonal antibody specific to nephrocalcin was raised in rabbits and the level of nephrocalcin was quantitatively determined in urine of 19 renal cell carcinoma patients (0.241 +/- 0.341 microgram nephrocalcin per mg. creatinine) and compared to healthy controls (0.022 +/- 0.012 micrograms nephrocalcin per mg. creatinine). Nephrocalcin levels after tumor nephrectomy decreased dramatically in 5 patients and to a lesser degree in 7. A specific nephrocalcin fraction that was eluted from an anion exchange column with low ionic strength was detected in urine of the renal cell carcinoma patients, and this fraction decreased or disappeared after tumor nephrectomy in 6 of 9 patients studied. Amino acid composition, phosphate content and dissociation constants toward calcium oxalate monohydrate crystals were investigated in the nephrocalcin from tumor patients and compared to that from healthy controls. Our studies demonstrate that nephrocalcin in patients with renal cell carcinoma is atypical and usually in much higher quantity. Further studies are needed to determine the clinical significance of these observations.