Renal epithelial cells constitutively produce a protein that blocks adhesion of crystals to their surface

Abstract

Attachment of newly formed crystals to renal tubular epithelial cells appears to be a critical step in the development of kidney stones. The present study was undertaken to identify autocrine factors released from renal epithelial cells into the culture medium that inhibit adhesion of calcium oxalate crystals to the cell surface. A 39-kDa glycoprotein that is constitutively secreted by renal cells was purified by gel filtration chromatography. Amino acid microsequencing revealed that it is novel and not structurally related to known inhibitors of calcium oxalate crystallization. Hence, it was named crystal adhesion inhibitor, or CAI. Immunoreactive CAI was detected in diverse rat tissues, including kidney, heart, pancreas, liver, and testis. Immunohistochemistry revealed that CAI is present in the renal cell cytosol and is also on the plasma membrane. Importantly, CAI is present in normal human urine, from which it can be purified using calcium oxalate monohydrate crystal affinity chromatography. CAI could be an important defense against crystal attachment to tubular cells and the subsequent development of renal stones in vivo.