Adhesion, internalization and metabolism of calcium oxalate monohydrate crystals by renal epithelial cells

The interaction between crystals that nucleate in the nephron lumen and tubular cells could be an important determinant of renal calcification. Kidney epithelial cells in monolayer culture (BSC-1 line), used to model the tubule, rapidly bound and internalized crystals of calcium oxalate monohydrate (COM), the most common constituent of renal stones. Transmission and scanning electron microscopy, enzyme histochemistry, and kinetic analysis of [14C]-labeled crystals were used to study the interaction between renal cells and COM crystals. Electron microscopy revealed that adherent crystals on the apical cell surface can serve as sites for aggregation of additional crystals. Enhanced binding of exogenous crystals to plasma membrane domains overlying internalized crystals was observed for at least 24 hours after the initial cell-crystal interaction. Following internalization, crystals appeared to dissolve within lysosomal inclusion bodies during the ensuing five to seven weeks. Over this time, many cells still containing crystals clustered together in the monolayer. These observations suggest that adhesion and internalization can promote crystal retention in the nephron, whereas intracellular dissolution of crystals may serve as an important, hitherto unrecognized defense against pathologic renal calcification.