Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals

Abstract

Renal epithelial cell injury causes crystal retention and leads to renal stone formation. However, the effects of crystal shape on cell injury and stone risk remain unclear. This study compared the cytotoxicity degrees of calcium oxalate dihydrate (COD) crystals having different shapes toward human kidney proximal tubular epithelial (HK-2) cells to reveal the effect of crystal shape on cell injury and to elucidate the pathological mechanism of calcium oxalate kidney stones. The effects of exposure to cross-shaped (COD-CS), flower-like (COD-FL), bipyramid (COD-BD), and elongated–bipyramid (COD-EBD) COD crystals on HK-2 cells were investigated by examining the cell viability, cell membrane integrity, cell morphology change, intracellular reactive oxygen species, mitochondrial membrane potential (Δψm), and apoptotic and/or necrotic rate. Crystals with large (100) faces (COD-EBD) and sharp edges (COD-CS) showed higher toxicity than COD-BD and COD-FL, respectively. COD crystal exposure caused cell membrane rupture, upregulated intracellular reactive oxygen, and decreased Δψm. This series of phenomena ultimately led to a high apoptotic rate and a low necrotic rate. Crystals with large active faces have a large contact area with epithelial cell surface, and crystals with sharp edges can easily scratch epithelial cells; these factors could promote crystal adhesion and aggregation, thus increasing stone risk.

Modulation of Calcium Oxalate Crystal Growth and Protection from Oxidatively Damaged Renal Epithelial Cells of Corn Silk Polysaccharides with Different Molecular Weights

“…This observation showed that the percentage of COM gradually decreased while COD gradually increased. Given that ν as (COO-) of COM and COD occur at 1,618 and 1,653 cm -1 , respectively, ν s (COO-) of COM and COD were 1,316 and 1,324 cm -1 , respectively (Figure 3(d)) [37,38]. The blue shift values of ν as (COO-) and ν s (COO-) depended on the percentage of COD crystals in the COM-COD mixture.…”

Structural Characterization and Repair Mechanism of Gracilaria lemaneiformis Sulfated Polysaccharides of Different Molecular Weights on Damaged Renal Epithelial Cells

“…Oxalic acid is a metabolism product of the human body and a main component for the formation of kidney stones. When oxalic acid in urine reaches a certain concentration, human kidney proximal tubular epithelial cells (HK-2 cells) will be oxidatively damaged [ 15 ], which is correlated with the formation of kidney stones [ 16 , 17 ]. The damaged cells can be repaired by plant polysaccharides [ 18 , 19 ].…”

Calcium oxalate crystal deposition in the kidney: identification, causes and consequences

“…In patients with hypercalciuria, the primary crystal deposited is CaP [2], this nidus may form the focus of aggregation for either CaP or CaOx [18] This variable aggregation has been demonstrated in vitro [19], in rat models [17,20], and observed in humans [2]. However, in patients with hyperoxaluria the predominant crystal type is CaOx [21]; this has again been demonstrated in a rat model [17], in vitro [4,5,22] and in humans [2].…”