Effect of Crystal Shape and Aggregation of Calcium Oxalate Monohydrate on Cellular Toxicity in Renal Epithelial Cells.

Abstract

Renal epithelial cell injury is a key step in inducing kidney stone formation. This injury induced by crystallites with different shapes and aggregation states has been receiving minimal research attention. To compare the shape and aggregation effects of calcium oxalate crystals on their toxicity, we prepared calcium oxalate monohydrate (COM) crystals with the morphology of a hexagonal lozenge, a thin hexagonal lozenge, and their corresponding aggregates. We then compared their toxicities toward human kidney proximal tubular epithelial (HK-2) cells. All four shapes of COM crystals caused cell-membrane rupture, upregulated intracellular reactive oxygen, and decreased mitochondrial membrane potential. This series of phenomena ultimately led to necrotic cell death. The overall damage in cells was determined in terms of both exterior and interior damage. Crystals with a large Ca2+ ion-rich (1̅01) active face showed the greatest toxicity in HK-2 cells and the largest extent of adhesion onto the cell surface. Crystals with sharp edges easily caused cell-membrane ruptures. The aggregation of sharp crystals aggravated cell injury, whereas the aggregation of blunt crystals weakened cell injury. Therefore, crystal shapes and aggregation states were important factors that affected crystal toxicity in renal epithelial cells. All of these findings elucidated the relationship between the physical properties of crystals and cytotoxicity and provided theoretical references for inhibiting stone formation.