尿NGAL在2型糖尿病肾病肾小管间质损伤评价中的价值

Value of urinary neutrophil gelatinase-associated lipocalin in evaluation of renal tubulointerstitial injury of type 2 diabetic nephropathy

目的探讨尿中性粒细胞明胶酶相关载脂蛋白(NGAL)对评价2型糖尿病肾病(DN)患者肾小管间质损伤的价值。方法研究对象为2012年1月至2015年12月第三军医大学大坪医院2型糖尿病患者167例(2型糖尿病组);将2型糖尿病组再分为正常白蛋白尿组(n=56)、微量白蛋白尿组(n=58)、大量白蛋白尿组(n=53),其中51例患者进行了肾活检。50例非糖尿病患者作为正常对照组。采用酶联免疫吸附测定方法检测尿液中NGAL水平,分光光度法测定尿N-乙酰-β-D-葡萄糖苷酶(NAG)。分析尿NGAL水平与肾功能相关指标[尿NAG、尿白蛋白/肌酐比值(ACR)、e GFR]及肾组织损伤病理评分之间的相关性,以及NGAL对DN肾小管间质损伤严重程度的评价效能,采用SPSS软件进行统计学分析,相关性分析采用Pearson或Spearman方法。结果糖尿病患者尿NGAL水平较非糖尿病正常对照组明显增加;尿NGAL水平与尿NAG、ACR呈正相关(r=0.528,0.578,P<0.001),与e GFR呈负相关(r=-0.637,P<0.001);尿NGAL水平与DN肾小管萎缩与间质纤维化(IFTA)的严重程度呈显著正相关(r=0.652,P<0.001);尿NGAL曲线下面积最大(AUC=0.868),特异度94.7%,敏感度71.9%。结论尿NGAL是评价DN肾小管间质损伤理想的生物标志物之一。

Objective To investigate the value of urinary neutrophil gelatinase-associated lipocalin （NGAL）in evaluation of renal tubulointerstitial injury of type 2 diabetic nephropathy （DN）.Methods 167 patients with type 2 diabetes and 50 patients without diabetes were recruited in this study from the Department of Nephrology of Daping Hospital from January of 2012 to December of 2015.The diabetic patients were categorized into normoalbuminuria group （n =56）,microalbuminuria group （n =58）,and macroalbuminuria group （n=53）,among whom 51 patients received renal biopsies.Urinary NGAL levels were measured by ELISA,and urinary NAG levels were measured by the spectrophotometric method. Analysis was made for correlation of urinary NGAL with renal function parameters, and with renal histopathological sores.The value of urinary NGAL in evaluation of renal tubulointerstitial injury of DN was also analyzed.Results Urinary NGAL levels were elevated in diabetic patients compared with the non-diabetes control.Urinary NGAL levels were positively associated with both urinary NAG （r=0.528,P〈0.001）and ACR （r =0.578,P〈0.001）,and negatively associated with eGFR （r =-0.637,P〈0.001）.Urinary NGAL levels were significantly correlated with scores of renal tubular atrophy and interstitial fibrosis （r=0.652,P〈0.001 ）in DN.Urinary NGAL had the largest area under the curve （AUC=0.868）,with a specificity of 94.7% and a sensitivity of 71.9%.Conclusion Urinary NGAL could serve as one of the most ideal biomarkers for evaluating the tubulointerstitial injury in DN.