| OBJECTIVE To detect the levels of urinary inflammatory cytokines MCP-1, TFF1 and HMGB1, investigate the relationship between urinary calcium and inflammatory cytokines, and explore the roles of inflammatory cytokines in nephrolithiasis formation and search the possible origin of inflammatory cytokines in patients with calcium nephrolithiasis.METHODS 81 patients with calcium nephrolithiasis were selected as experimental group marked as CN.30 people without urinary disease were randomly selected as control group marked as C. Cytokines MCP-1, TFF1, HMGB1 in urine were tested by ELISA. MCP-1, TFF1, HMGB1 in urina sanguinis of group CN were compared with group C after both normalizing with creatinine of urina sanguinis. According to the level of urinary calcium, group CN were further divided into two groups, group H:the 24 h urine calcium≥ 4 mg/kg/d,32 cases; group N:the 24 h urine calcium< 4 mg/kg/d,49 cases. MCP-1, TFF1, HMGB1 in urina sanguinis of group H, group N and group C were compared in pairs after normalizing with creatinine of urina sanguinis. Renal tissues obtained from 3 patients in group CN were marked as experimental group of IHC(group E-IHC), while normal part of renal tissue form 2 renal carcinoma patients was marked as control group of IHC (group C-IHC). The expression of MCP-1, TFF1 and HMGB1 in group E-ICH and group C-ICH were observed by immunohistochemistry.RESULTS The levels of MCP-1 and HMGB1 in group CN was higher than group C (p< 0.05), The level of TFF1 was no significant different between group CN and group C (p> 0.05). Furthermore, statistics showed that the levels of MCP-1 and HMGB1 in calcium nephrolithiasis patients, both group H and group N were higher than group C (p< 0.05), but there were no significant different between the group H and group N (p> 0.05). Compared with the other two groups, TFF1 in group H decreased (p< 0.05), there were no significant different between the group N and group C (p> 0.05). Correlation analysis showed that there was a positive correlation between urinary calcium level and urinary MCP-1 level, but the correlation between urinary calcium level and urinary TFF1 level was negative in group H. There was no statistically significant correlation between urinary calcium level and urinary HMGB1 level. In all samples of 111 cases, there was a positive correlation between urinary TFF1 level and urinary MCP-1 level. Immunohistochemical staining suggested that MCP-1, TFF1, HMGB1 all expressed in both group E-IHC and group C-IHC, and the expression location were mainly in the proximal and distal renal tubule, the thin segment of Henle loop and the collecting duct epithelium.CONCLUTIONS Compared with control group, there were significantly increase in the levels of urinary MCP-1 and HMGBl in calcium nephrolithiasis patients. Experiment results indicated that MCP-1, HMGB1 might contribute to the formation of calcium oxalate stone. As an independent factor, hypercalciuria prompts the decrease of urinary TFF1 level, while have no effect on urinary MCP-1 and HMGB1 levels in calcium nephrolithiasis patients. It indicated that the increase of urinary MCP-1 and HMGB1 levels might be the results of interaction of multi-factors injury, including nephrolithiasis. Renal pathology analysis indicated that MCP-1, TFF1 and HMGB1 both expressed in the kidney. These inflammatory cytokines in urine are probably from the impaired renal tubule and/or collecting tube epithelium. |
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