OBJECTIVE To address whether hypercalciuria can stimulate calcium oxalate (CaOx) crystal deposition in kidney through osteopontin (OPN). MATERIALS AND METHODS Rat tubular epithelial NRK cells were exposed to calcium. The cell viability, the cellular malondialdehyde content as a marker of reactive oxygen species (ROS), and the release of lactate dehydrogenase as markers of injury were detected. The production and gene expression of OPN were also examined. CaOx crystal attachment to cells was accomplished by measuring the calcium concentration of the cell lysates with atomic absorption analysis. RESULTS Exposure to calcium produced signs of cell injury and ROS-induced lipid peroxidation. The messenger ribonucleic acid expression and production of OPN increased significantly. OPN knockdown can significantly decrease the amount of CaOx crystal attachment to NRK cells. CONCLUSION In response to exposure to high concentration of calcium, renal tubular epithelial NRK cells increase the production of OPN, which may have a promoting role in CaOx crystal adhesion to NRK cells by calcium stimulation. (C) 2015 Elsevier Inc.