Urinary calprotectin,NGAL, and KIM-1 in the differentiation of primarily inflammatory vs. non-inflammatory stable chronic kidney diseases

Introduction It has been demonstrated that urinary neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin are helpful biomarkers in the differentiation of intrinsic and prerenal acute kidney injury.Objective The present cross-sectional study investigates, whether urinary biomarkers are able to differentiate primarily inflammatory from non-inflammatory entities in chronic kidney disease (CKD).Methods Urinary calprotectin, NGAL, and kidney injury molecule-1 (KIM-1) concentrations were assessed in a study population of 143 patients with stable CKD and 29 healthy controls. Stable renal function was defined as an eGFR fluctuation ≤5 ml/min/1.73 m² in the past 12 months. Pyuria, metastatic carcinoma, and renal transplantation were regarded as exclusion criteria. Diabetic nephropathy, hypertensive nephropathy, and polycystic kidney disease were categorized as ‘primarily non-inflammatory renal diseases’ (NIRD), whereas glomerulonephritis and vasculitis were regarded as ‘primarily inflammatory renal diseases’ (IRD).Results Urinary calprotectin and NGAL concentrations significantly differed between CKD and healthy controls (p < 0.05 each), whereas KIM-1 concentrations did not (p = 0.84). The three biomarkers did neither show significant differences in-between the individual entities, nor the two categories of IRD vs. NIRD (calprotectin 155.7 vs. 96.99 ng/ml; NGAL 14 896 vs. 11 977 pg/ml; KIM-1 1388 vs. 1009 pg/ml; p > 0.05 each). Albumin exceeds the diagnostic power of the investigated biomarkers by far.Conclusions The urinary biomarkers calprotectin, NGAL, and KIM-1 have no diagnostic value in the differentiation of primarily inflammatory vs. non-inflammatory etiologies of CKD.     

NGAL滤过分数在2型糖尿病患者中的临床意义

目的研究中性粒细胞明胶酶相关脂质运载蛋白（NGAL）在2型糖尿病患者血、尿中的表达,探讨其滤过分数在2型糖尿病患者中的临床意义。方法选择2型糖尿病患者118例及正常对照28例,根据尿白蛋白／肌酐比值（UACR）将患者分为三组,即UACR〈30mg／g的正常蛋白尿组64例,30mg／g≤UACR〈300m晚的微量白蛋白尿组36例,UACR≥300mg／g的大量白蛋白尿组18例。应用ELISA法测定各组血、尿中的NGAL的含量,常规方法测定血、尿肌酐等其它常用临床指标,按照BdignanoD提出公式计算NGAL滤过分数（FeNGAL）,按照Macisaac公式估算GFR,统计分析FeNGAL与常用临床指标的相关性。结果（1）DM患者FeNGAL均明显高于正常对照组;三组间呈递增改变且差异有显著性（P〈0．05）;（2）FeNGAL与胱抑素C、UACR成正相关（R分别为0．279,0．485）,与eGFR成负相关（R=-0．235）。结论FeNGAL可早期反映DM患者肾脏损害程度,且优于尿微量白蛋白及单一血、尿NGAL。     

NGAL 及 MMP9在原发性肝癌患者血清中表达及意义

目的：探讨原发性肝癌（PHC）患者血清中性粒细胞明胶酶相关脂质运载蛋白（NGAL ）及基质金属蛋白酶9（MMP9）的变化及临床意义。方法采用酶联免疫吸附测定（ELISA）检测47例 PHC 患者（PHC 组）及19例健康体检者健康血清中 NGAL 及 MMP9水平,并分析二者与临床病理的联系,同时使用 ROC 曲线分析二者对 PHC 的诊断价值,Kaplan-Meier 生存曲线分析不同 NGAL 、MMP9水平的生存差异。结果 PHC 组 NGAL 、MMP9水平明显高于健康体检者对照组,差异有统计学意义（P＜0．05）;NGAL 及 MMP9的水平在Ⅲ～Ⅳ期组高于Ⅰ～Ⅱ期,差异有统计学意义（P ＜0．05）;血清 MMP9、NGAL 检测灵敏度分别为70．2％和83．0％。二者联合检测可提高灵敏度至94．9％。 Kaplan-Meier 生存分析发现血清 NGAL 水平高患者预后差。结论 PHC 患者血清 NGAL 及 MMP9与 PHC 的发生、发展密切相关;联合检测血清水平 NGAL 及 MMP9可明显提高敏感度,对 PHC 诊断及预后指标有一定的价值。     

NGAL和KIM-1检测在儿童脓毒症合并急性肾损伤中的诊断价值

 目的 探讨中性粒细胞明胶酶相关脂质运载蛋白（neutrophil gelatinase-associated lipocalin,NGAL）和肾损伤因子1（kidney injury molecule 1,KIM-1）的检测在脓毒症合并急性肾损伤（acute kidney injury,AKI）患儿诊疗过程中的临床应用价值。方法 采用病例对照研究,按照纳入标准选取2019年1-12月入住复旦大学附属儿科医院PICU的脓毒症患儿82例,按照排除标准去除13例。按入院后是否发生AKI分为脓毒症AKI组28例和脓毒症非AKI组41例。脓毒症AKI组患儿根据治疗过程中是否进行连续性肾脏替代治疗（continuous renal replacement therapy,CRRT）分为脓毒症AKI-CRRT组和脓毒症AKI-非CRRT组。检测脓毒症AKI和非AKI患儿住院后0 h、24 h和72 h的血NGAL、KIM-1、肌酐、胱抑素C（cystatin C,CysC）和视黄醇结合蛋白（retinol-binding protein,RBP）水平,同时监测24 h和72 h的尿量。用非参数检验统计方法分析数据,通过受试者工作特征（receiver operating characteristic,ROC）曲线分析NGAL、KIM-1、肌酐、尿量、CysC、RBP对脓毒症并发AKI的诊断价值。结果 脓毒症AKI组患儿的NGAL、KIM-1、肌酐、CysC水平在0 h、24 h、72 h时均显著高于脓毒症非AKI组（P<0.05）。脓毒症AKI-CRRT组和非CRRT组各时点NGAL、肌酐的水平均高于脓毒症非AKI组（P<0.05）。KIM-1、CysC、RBP、尿量在24 h和72 h时,脓毒症AKI患儿较非AKI患儿有明显差异（P<0.05）。ROC曲线比较显示：脓毒症AKI-CRRT组和非CRRT组0 h时NGAL的AUC面积均最大（分别为0.907和0.951）、灵敏度最高（分别为92%和100%）。脓毒症AKI-CRTT组患儿的肌酐水平在72 h时呈现下降,并且较24 h时肌酐的AUC面积减小、敏感度和特异性均降低（P<0.05）;NGAL和KIM-1水平在24 h显著升高后,至72 h仍维持在较高水平,且NGAL在3个时点、KIM-1在后2个时点均维持良好的诊断效能。结论 NGAL灵敏度较高,可在早期提示AKI的发生。在血液净化的治疗过程中NGAL、KIM-1受干扰因素较少,可为AKI患儿肾功能真实水平的评估提供参考。     

Novel Risk Factors for Progression of Diabetic and Nondiabetic CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

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Predicting long-term outcomes after cardiac arrest by using serum neutrophil gelatinase-associated lipocalin

Objectives

Neutrophil gelatinase-associated lipocalin (NGAL) is secreted by various tissues in pathologic states. Previous studies reported that post-cardiac arrest serum NGAL levels correlate with short-term neurologic outcomes and survival. The aim of this study was to examine the associations between NGAL levels post-cardiac arrest and long-term outcomes and survival.

KIM-1及NGAL在苯酚烧伤致大鼠早期肾损伤中的表达水平及意义

目的 观察肾损伤分子-1（KIM-1）及中性粒细胞明胶酶相关载脂蛋白（NGAL）在苯酚烧伤致大鼠早期肾损伤中的表达水平,并分析其临床意义。方法 将48只SD大鼠随机分为对照组6只、实验组42只,对照组大鼠仅做背部脱毛处理,实验组大鼠建立苯酚烧伤模型,分别于烧伤后15、45 min以及2、4、8、16、32 h观察肾脏组织病理变化,并采用酶联免疫吸附试验（ELISA）法检测KIM-1、NGAL水平,肌氨酸氧化酶法检测血肌酐（Scr）水平,分析KIM-1、NGAL与肾损伤的相关性及其对肾损伤的诊断价值。结果 苯酚烧伤大鼠创面呈浅红色至棕红色、质地稍韧,且伴有全身抽搐及肉眼血尿等表现;苏木精-伊红（HE）染色结果显示,烧伤32 h内大鼠肾脏组织逐渐出现肾小管空泡样变性、蛋白质管型、肾小管扩张、肾小管坏死等病理改变;烧伤后32 h内大鼠血清KIM-1、NGAL水平均呈先升高后降低的趋势,其中KIM-1水平于烧伤后15 min开始升高,8 h到达高峰;NGAL水平于烧伤后2 h开始升高,16 h到达高峰;而Scr水平升高不明显;血清KIM-1、NGAL水平与早期肾损伤具有显著相关性（r=0.664、0.730,P均＜0.001）,两者联合检测对诊断早期肾损伤具有显著优势。结论 血清KIM-1及NGAL水平与苯酚烧伤致大鼠早期肾损伤程度密切相关,对诊断苯酚烧伤致大鼠早期肾损伤具有较高的临床应用价值。