Regulation of renal epithelial cell endocytosis of calcium oxalate monohydrate crystals

The earliest events in the formation of kidney stones are unknown. The most common crystal in kidney stones, calcium oxalate monohydrate (COM), when added to cultures of monkey kidney epithelial cells (BSC-1 line), was internalized by 19% of the cells after 30 min. COM crystal endocytosis was enhanced by serum, ADP, and epidermal growth factor, which are potent mitogens for these cells. Endocytosis of COM crystals was inhibited by diverse molecules including Tamm-Horsfall glycoprotein (THP), the tetrapeptide arginine-glycine-aspartic acid-serine, fibronectin, transforming growth factor-β2, and heparin. The capacity of THP, fibronectin, or heparin to inhibit endocytosis was mediated by an interaction of these molecules with cells, not by coating the crystals. Thus renal epithelial cell endocytosis of COM crystals can be regulated by diverse molecules including THP, the most common protein found in human urine. Crystal endocytosis and subsequent cellular responses could be important pathogenic steps in nephrolithiasis.