Nucleation, adhesion, and internalization of calcium-containing urinary crystals by renal cells

Renal tubular fluid in the distal nephron is supersaturated favoring nuclea tion of the most common crystals in renal stones, which are composed of cal cium oxalate and calcium phosphate. The mechanisms whereby these newly form ed crystals can be retained in the nephron and develop into calculi are not known. Calcium oxalate monohydrate and hydroxyapatite (calcium phosphate) crystals rapidly adhere to anionic sites on the surface of cultured renal e pithelial cells, but this process is inhibited by specific urinary anions s uch as citrate, glycosaminoglycans, uropontin, or nephrocalcin, each of whi ch can coat the crystals. Therefore, competition for the crystal surface be tween soluble anions in tubular fluid and anions anchored on the epical cel l surface could determine whether a crystal binds to a tubular cell. Crysta ls of calcium oxalate dihydrate can also nucleate directly on the surface o f cultured BSC-1 cells in a face-specific manner, suggesting another potent ial pathway for crystal deposition in the nephron. Once present on the cell surface, calcium oxalate monohydrate, calcium oxalate dihydrate, and hydro xyapatite crystals are quickly internalized by renal cells; alterations in gene expression and initiation of proliferation may then ensue. Calcium oxa late crystals can also dissolve after renal cells internalize them, but thi s process may require up to several weeks. Increased knowledge about cell-c rystal interactions, including identification of molecules in tubular fluid and on the cell surface that modulate the process, appear critical for und erstanding the pathogenesis of nephrolithiasis.