尿KIM-1和NGAL在评估慢性肾脏病肾小管间质损伤中的作用

Role of urinary KIM-1 and NGAL in evaluating tubulointerstitial injury in chronic kidney disease

目的测定慢性肾脏病(CKD)患者尿液中的肾损伤分子-1(KIM-1)及中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的水平,评估KIM-1及NGAL在CKD肾小管间质损伤患者中的治疗价值。方法选取中国医科大学附属盛京医院2017年2-9月诊断为CKD的患者作为分析样本,同时,通过肾脏病理组织检查将其中确定存在肾小管间质损伤患者103例设为试验组。在此基础上,对肾小管间质病变进行半定量分级,并参照Banff病理评价标准将患者细分为3个不同的试验组,即重度、轻-中度和轻度损伤组。同时选取该院体检中心体检健康者17例为健康对照组。采用酶联免疫吸附试验(ELISA)法测定尿KIM-1以及NGAL的水平,收集试验组患者各项临床指标,包括血红蛋白、24h尿蛋白定量等,评估KIM-1与NGAL与各项指标及肾小管间质病变的相关性。结果 3个不同试验组与健康对照组之间年龄、性别构成比差异无统计学意义(P>0.05)。尿KIM-1在健康对照组与轻度损伤组,轻-中度损伤组与重度损伤组组间比较,差异无统计学意义(P>0.05),其他两组之间通过对比发现基本都具有统计学意义(P<0.05)。比较轻-中度损伤组、轻度损伤组的尿NGAL差异不具有统计学意义(P>0.05),但是,剩余两组之间则有显著性差异(P<0.05)。另外,尿KIM-1与eGFR(r=-0.33,P=0.001)、血红蛋白具有显著的负相关关系(r=-0.25,P=0.01);与肾小管间质损伤程度(r=0.60,P<0.001)、胱抑素C(r=0.26,P=0.01)等指标之间具有显著的正相关关系;尿NGAL与eGFR(r=-0.64,P<0.001)、血红蛋白(r=-0.43,P<0.001)呈负相关性。与肾小管间质损伤程度(r=0.76,P<0.001)、肌酐(r=0.63,P<0.001)、尿素氮(r=0.62,P<0.001)、胱抑素C(r=0.37,P<0.001)呈正相关性。尿KIM-1诊断肾小管间质损伤的受试者工作特征曲线(ROC曲线)下面积为0.88,最佳临界点为2.13ng/mL,而尿NGAL曲线下面积为0.97,最佳临界点为4.62ng/mL。尿KIM-1在轻度损伤组的ROC曲线下特异度和灵敏度分别为88%、68%,而曲线下面积为0.80,但是,尿NGAL曲线下面积为0.94,灵敏度为95%,特异度为88%。结论尿KIM-1与尿NGAL测定均可以评估CKD患者肾小管间质损伤程度,而NGAL对肾小管间质损伤程度,尤其针对早期损伤具有更好的评估价值。

Objective To determine the levels of kidney injury molecule-1(KIM-1)and neutrophil gelatinase-related lipid carrier protein(NGAL)in urine of patients with chronic kidney disease(CKD).To study the value of treatment of KIM-1 and NGAL in renal tubulointerstitial injury of CKD.Methods The CKD diagnosis results of Shengjing Hospital affiliated to China Medical University from February to September 2017 were selected as analysis samples.At the same time,103 patients in the samples with renal tubulointerstitial injury confirmed by renal biopsy were set as experimental group.According to Banff's pathological scoring criteria,renal tubulointerstitial lesions were semi-quantitatively graded,the patients were divided into mild injury group,mild-moderate injury group and severe injury group.At the same time,17 healthy persons in the physical examination center of the hospital were selected as healthy control group.The levels of urinary KIM-1 and NGAL were measured by ELISA.The clinical indicators including Hemoglobin,24h urine protein,etc.to evaluate the correlation between KIM-1 and NGAL with various indicators and tubulointerstitial lesions.Results There was no significant difference in age and sex composition between the experimental group and the healthy control group(P>0.05).Urine KIM-1 has no statistical significance in comparison between the control group and mild injury group,between the light and moderate injury group and severe injury group(P>0.05).There was significant difference between the other two groups(P<0.05).Comparing the difference of urinary NGAL between mild and moderate injury group and mild injury group(P>0.05),which is not statistically significant,but there is significant difference between the remaining two groups(P<0.05).In addition,urine KIM-1 has a significant inverse proportional relationship with eEGFR(r=-0.33,P=0.001)and hemoglobin(r=-0.25,P=0.01);There is a significant positive proportional relationship with the indexes of tubulointerstitial injury degree(r=0.60,P<0.001),cystatin C(r=0.26,P=0.01).Urine NGAL was negatively correlated with eGFR(r=-0.64,P<0.001),hemoglobin(r=-0.43,P<0.001),and positively correlated with tubulointerstitial injury(r=0.76,P<0.001),creatinine(r=0.63,P<0.001),urea nitrogen(r=0.62,P<0.001),cystatin C(r=0.37,P<0.001).The area under the ROC curve of urinary KIM-1 for diagnosis of tubulointerstitial injury was 0.88,the optimal threshold was 2.13 ng/mL,while the area under urinary NGAL curve was 0.97 and the optimal threshold was 4.62 ng/mL.In mild injury group,the area under ROC curve of urinary KIM-1 was 0.80,the sensitivity was 68%,the specificity was 88%,but the specificity and sensitivity of urine NGAL curve were 88% and 95% respectively,while the area was 0.94.Conclusion Both urinary KIM-1 and urinary NGAL can evaluate the severity of tubulointerstitial lesion in CKD patients.NGAL has better value in evaluating the severity of tubulointerstitial injury,especially for early injury.