Urine hepcidin, netrin-1, neutrophil gelatinase-associated lipocalin and C-C motif chemokine ligand 2 levels in multicystic dysplastic kidney

ABSTRACT Introduction: Glomerular hyperfiltration may lead to proteinuria and chronic kidney disease in unilateral multicystic dysplastic kidney (MCDK). We aimed to investigate the urine neutrophil-gelatinase-associated lipocalin (NGAL), netrin-1, hepcidin, and C-C motif chemokine ligand-2 (MCP-1/CCL-2) levels in patients with MCDK. Methods: Thirty-two patients and 25 controls were included. The urine hepcidin, netrin-1, NGAL, and MCP-1/CCL-2 levels were determined by ELISA. Results: The patients had higher serum creatinine (Cr) levels, urine albumin, and netrin-1/Cr ratio with lower GFR. There were positive correlations between urine protein/Cr, MCP-1/CCL-2/Cr, and netrin-1 with NGAL (r = 0.397, p = 0.031; r = 0.437, p = 0.041, r = 0.323, p = 0.042, respectively). Urine netrin-1/Cr was positively correlated with MCP-1/CCL-2/Cr (r = 0.356, p = 0.045). There were positive associations between the presence of proteinuria and netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr [Odds ratio (OR): 1.423, p = 0.037, OR: 1.553, p = 0.033, OR: 2.112, p = 0.027, respectively)]. ROC curve analysis showed that netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr had high predictive values for determining proteinuria p = 0.027, p = 0.041, p = 0.035, respectively). Urine hepcidin/Cr was negatively correlated with tubular phosphorus reabsorption and was positively correlated with urine NGAL/Cr (r = -0.418, p = 0.019; r = 0.682, p = 0.000; respectively). Conclusions: MCP-1/CCL-2 may play a role in the development of proteinuria in MCDK. Netrin-1 may be a protective factor against proteinuria-induced renal injury. Urine hepcidin/Cr may reflect proximal tubule damage in MCDK. Urine NGAL/Cr may be a predictor of tubule damage by proteinuria.

摘要
引言：单侧多囊发育不良肾（unilateral multicystic dysplastic kidney, MCDK）患者的肾小球高滤过状态可能引发蛋白尿与慢性肾脏病。本研究旨在探讨MCDK患者尿液中性粒细胞明胶酶相关脂质运载蛋白（neutrophil-gelatinase-associated lipocalin, NGAL）、轴突导向蛋白1（netrin-1）、铁调素（hepcidin）以及C-C基序趋化因子配体2（C-C motif chemokine ligand-2, MCP-1/CCL-2）的表达水平。

方法：本研究纳入32例MCDK患者与25例健康对照人群，采用酶联免疫吸附试验（enzyme-linked immunosorbent assay, ELISA）检测尿液中铁调素、netrin-1、NGAL及MCP-1/CCL-2的浓度。

结果：患者组的血清肌酐（serum creatinine, Cr）水平、尿白蛋白含量及netrin-1/Cr比值显著升高，而肾小球滤过率（glomerular filtration rate, GFR）则更低。尿蛋白/Cr比值、MCP-1/CCL-2/Cr比值与netrin-1水平均与NGAL水平呈正相关（相关系数r分别为0.397、0.437、0.323，对应P值依次为0.031、0.041、0.042）。尿netrin-1/Cr比值与MCP-1/CCL-2/Cr比值亦呈正相关（r=0.356，P=0.045）。蛋白尿阳性与netrin-1/Cr、MCP-1/CCL-2/Cr及NGAL/Cr比值存在显著正相关关联[比值比（odds ratio, OR）分别为1.423、1.553、2.112，对应P值依次为0.037、0.033、0.027]。受试者工作特征（receiver operating characteristic, ROC）曲线分析显示，netrin-1/Cr、MCP-1/CCL-2/Cr及NGAL/Cr比值对蛋白尿具有较高的预测价值，对应P值分别为0.027、0.041、0.035。尿铁调素/Cr比值与肾小管磷重吸收率呈负相关，而与尿NGAL/Cr比值呈正相关（r=-0.418，P=0.019；r=0.682，P<0.001）。

结论：MCP-1/CCL-2可能参与MCDK患者蛋白尿的发生发展进程。Netrin-1或可作为对抗蛋白尿诱导肾损伤的保护性因子。尿铁调素/Cr比值可反映MCDK患者的近端肾小管损伤情况。尿NGAL/Cr比值或可作为蛋白尿所致肾小管损伤的预测指标。