Urinary MCP-1、HMGB1 increased in calcium nephrolithiasis patients and the influence of hypercalciuria on the production of the two cytokines.

The study aims to observe the urinary excretion of monocyte chemoattractant-1 (MCP-1) and high-mobility group box 1 (HMGB1) in patients with calcium nephrolithiasis and to determine the influence of hypercalciuria on the production of the two cytokines. 81 cases of patients with calcium nephrolithiasis (group CN) and 30 healthy controls (group C) were involved in this study. To observe the influence of urinary calcium on the excretion of those cytokines, the patients were subdivided according to their 24-h urinary calcium level: ≥4 mg/kg/day (group H) and <4 mg/kg/day (group N). MCP-1 and HMGB1 in urina sanguinis were determined for all subjects. In addition, in vitro study was done to determine the production of the two cytokines and index of apoptosis and oxidative injuries in human kidney epithelial cells (HK-2) exposed to three high levels of calcium. Data showed that both urinary MCP-1 and HMGB1 in group CN were higher than that of group C. When the patients were subdivided, comparisons among the three groups showed that both MCP-1 and HMGB1 in group H and group N were higher than group C, but there was no significant statistical difference between the two stone groups. In vitro study, the apoptosis rate of cells, the lactate dehydrogenase activities, the hydrogen peroxide, and 8-isoprostane concentrations in the medium all increased in accordance with the increased concentration of calcium supplemented. Compared with the control, mRNA expressions of MCP-1 and HMGB1 in cells and the protein concentrations of the two cytokines in the medium of calcium-supplemented groups increased significantly. Results showed that urinary MCP-1 and HMGB1 increased in calcium nephrolithiasis patients and hypercalciuria might affect the identical pathways (through the reactive oxygen species) with other factors in stimulating the production of MCP-1 and HMGB1 in vivo.