白细胞介素18、中性粒细胞明胶酶相关脂质运载蛋白和血清胱抑素C在呼吸衰竭合并急性肾损伤中的变化

目的探讨尿白细胞介素18（interleukin-18,IL-18）、中性粒细胞明胶酶相关脂质运载蛋白（neutrophilgelatinase-associatedlipocalin,NGAL）和血清胱抑素C（cystatinC,Cysc）在呼吸衰竭合并急性肾损伤（acutekidneyinjury,AKI）中的变化。方法收集我院呼吸衰竭患者125例,其中呼吸衰竭并发AKI患者35例（AKI组）,呼吸衰竭未并发AKI患者90例（非AKI组）。检测全血细胞、血清CysC、血肌酐（SCr）、尿素氮（BUN）、血白蛋白水平、血气分析,检测尿NGAL和IL-18水平。结果2组患者间年龄、男女比例、动脉血氧分压、动脉血二氧化碳分压、血红蛋白、白蛋白的差异无统计学意义,而基础有高血压史比例的差异有统计学意义（P〈0．05）。AKI组估算肾小球滤过率（estimatedglomerularfiltrationrate,eGFR）低于非AKI组,差异有统计学意义（P〈0．05）;AKI组SCr、BUN、血清CysC、尿NGAL和II,18高于非AKI组,差异有统计学意义（P〈0．05）;Pearson相关分析显示AKI组尿IL-18、NGAL及血清CysC均与SCr具有相关性,与eGFR也具有相关性。多因素Logistic回归分析显示尿IL-18、NGAL、血清CysC升高是呼吸衰竭发生AKI的独立危险因素。结论尿IL-18、NGAL和血清CysC对诊断呼吸衰竭合并AKI有较高的准确性。     

粒细胞明胶酶相关脂质运载蛋白预测肝移植后急性肾损伤

肝移植后急性肾损伤（acute kidney injury,AKI）的发生率为48%～91%,影响受者的预后。发生AKI后接受肾脏替代治疗受者的病死率从术后90d的40%增至术后1年的54%。近来的研究显示血清粒细胞明胶酶相关脂质运载蛋白（neutrophil gelatinase-associated lipocalin,NGAL）和半胱氨酸蛋白酶抑制剂-C（cystatin C）均能较好地预测AKI的发生。     

原发性肾病综合征患者中性粒细胞明胶酶相关脂质运载蛋白的变化及意义

目的 探讨原发性肾病综合征(PNS)患者中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的变化以及与病理类型、肾小管间质损伤程度、临床指标的关系. 方法 40例PNS患者按有无急性肾小管坏死(ATN)分急性肾损伤(AKI)组及非AKI组,按病理类型分微小病变型肾病(MCD)组、系膜增生性肾小球肾炎(MsPGN)组、局灶性节段性肾小球硬化(FSGS)组、膜增生性肾小球肾炎(MPGN)组、膜性肾病(MN)组;20例健康体检者及20例因肾肿瘤做肾切除术但远离肿瘤部位的正常肾组织作正常对照.采用酶联免疫吸附试验(ELISA)法检测血清、尿液NGAL水平,免疫组织化学染色法观察肾组织NGAL表达.结果 (1) AKI组患者血、尿NGAL水平及肾组织NGAL表达显著高于非AKI组及对照组(P＜0.05).(2)MPGN组及FSGS组患者血、尿NGAL水平及肾组织NGAL表达显著高于其他病理类型组(P＜0.05).(3)在肾小管间质发展至重度病变之前,随着肾小管间质损伤程度的加重,血、尿NGAL水平及肾组织NGAL表达逐渐升高;在肾小管间质发展至重度病变时,血NGAL水平及肾组织NGAL表达下降(P＜0.05).(4)血、尿NGAL水平及肾组织NGAL表达与血肌酐呈正相关(r值分别为0.198、0.352、0.146,P值分别为0.048、0.000、0.028),与尿素氮呈正相关(r值分别为0.199、0.278、0.325,P值分别为0.043、0.000、0.019),与血白蛋白呈负相关(r值分别为-0.384、-0.318、-0.259,P值分别为0.028、0.024、0.020),与尿渗透浓度呈负相关(r值分别为-0.250、-0.256、-0.277,P值分别为0.012、0.027、0.002).结论 NGAL可作为预测PNS患者AKI的敏感指标,在一定程度下可用于评价肾小管间质病变程度及肾功能.     

中性粒细胞明胶酶相关脂质运载蛋白作用于肿瘤的二重性

中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在多种恶性肿瘤中都有不同程度的表达升高,并参与肿瘤的发生发展,但其对肿瘤的作用似乎存在相互矛盾的二重性.例如在乳腺癌和食管癌中通过保护MMP-9的自身降解,NGAL可促进肿瘤生长和转移.然而在胰腺癌和卵巢癌中.NGAL可通过抑制FAK的磷酸化和VEGF的合成而起到了抑制肿瘤演...     

尿中性粒细胞明胶酶相关载脂蛋白联合降钙素原对脓毒症急性肾损伤的预测价值

目的:探讨尿中性粒细胞明胶酶相关载脂蛋白(NGAL)联合降钙素原(PCT)对脓毒症急性肾损伤(AKI)患者的预测价值。方法:收集2018年6月至2020年1月本院收治的脓毒症患者89例,根据是否出现AKI分为非AKI组(40例)和AKI组(49例),入院后收集1、6、12、24 h的静脉血和尿液,采用酶联免疫吸附试验(...     

急性胰腺炎患者外周血血浆中中性粒细胞明胶酶相关脂质运载蛋白的浓度变化及其意义

目的:检测分析急性胰腺炎(AP)患者外周血中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的动态变化及其临床意义。方法:选取收治的117例AP患者,依据病情分为急性轻症胰腺炎(轻症组)60例,急性重症胰腺炎(重症组)57例;同时选取体检中心收集的健康自愿者60例作为健康组,分别检测三组研究对象的NGAL等指标并进行统计分析。结果:在入院后第1、3、7天重症组患者的外周血抵抗素、hs-CRP、NGAL、血淀粉酶、PCT测定值均显著的高于轻症组和健康组(P0.05);轻症组患者入院后第1、3天的外周血抵抗素、hs-CRP、NGAL、血淀粉酶、PCT测定值显著的高于健康组(P0.05);轻症组患者入院后第7天的血淀粉酶、PCT测定值显著的高于健康组(P0.05)。重症组患者的APACHE II评分在入院后第1、3、7天均显著的高于轻症组患者(P0.05)。重症组患者的Balthazar CT评分在入院后第1、7天均显著的高于轻症组患者(P0.05)。AP患者外周血NGAL水平与其外周血抵抗素、hs-CRP、PCT、PACHE II评分、Balthazar CT评分均呈正相关(P0.05)。结论:NGAL与AP患者病情严重程度具有显著关系,可作为临床治疗重要的参考指标。     

中性粒细胞明胶酶相关脂质运载蛋白、和肽素及血肌酐在窒息足月新生儿缺氧性肾损伤中的临床价值

目的探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、和肽素、血肌酐在窒息足月新生儿缺氧性肾损伤中的临床价值。方法选择2015年6月至2017年10月期间在河北省人民医院出生的1 000名婴儿中的48名足月新生儿为研究对象进行前瞻性研究,其中包括患有急性肾损伤(AKI)的9名窒息新生儿和39名窒息但无AKI迹象新生儿,另选取30名健康新生儿作为对照组。测量受试者的脐带血和出生后24h血液中NGAL、和肽素及肌酐的浓度。结果研究结果显示AKI组、非AKI组和对照组在脐带血中以及出生后24h血液中肌酐、和肽素水平以及血清渗透压无显著性差异。AKI组新生儿中,脐带血的NGAL和出生后24h的血液NGAL水平明显高于非AKI组和对照组。NGAL浓度与脐动脉pH (ρ=-0. 42,P=0. 04)、碱基过量(ρ=-0.31,P=0. 03)和Apgar评分在出生后第1分钟(ρ=-0. 41,P=0. 02)以及在第5分钟评分(ρ=-0. 20,P=0. 001)呈显著负相关。ROC曲线分析显示,出生后24h血液NGAL水平具有良好的预测价值(140. 7 ng/mL),可用于预测窒息新生儿的AKI发生。结论出生后24h血液NGAL是一个很有前景的物质,由于其具有高灵敏度、高特异性,可以作为早期预测窒息足月新生儿发生缺氧性肾损伤的标志物,但是和肽素与血肌酐并没有达到预期作为预测标志物的要求。     

慢性肾脏病患者血清中性粒细胞明胶酶相关脂质运载蛋白、胱抑素c的改变及其临床意义

目的:探讨慢性肾脏病(CKD)患者血NGAL、胱抑素c的改变及其临床意义。方法:选择原发性慢性肾小球肾炎所致的CKD2～4期患者共92例:其中CKD2期患者34例,CKD3期患者30例,CKD4期患者28例。同时以健康人20例作为对照。用ELISA法检测血清中NGAL的浓度,用免疫比浊法检测血清胱抑素c浓度。分析NGAL与胱抑素c、血肌酐、肾小球滤过率(GFR)之间的相关性。结果:(1)CKD2期、3期、4期血NGAL浓度,与对照组浓度比显著升高,P均<0.01。CKD2期、3期、4期胱抑素c浓度,与对照组浓度比显著升高,P均<0.01。CKD3期、4期血肌酐浓度,与对照组比P均<0.01;CKD2期与对照组比,差异无统计学意义(P>0.05)。(2)Pearson相关分析:血NGAL与胱抑素c、血肌酐呈正相关。血NGAL和血胱抑素c的水平均与GFR存在负相关。结论:CKD2～4期患者血NGAL、胱抑素水平升高,且血NGAL与血胱抑素c、血肌酐成正相关、与GFR负相关,血NGAL可作为CKD患者肾功能受损的新的标志物。     

急性肾损伤生物学标志物在心脏外科术后的研究进展

急性肾损伤是心脏外科手术后常见的严重并发症,发病率和病死率均较高.血肌酐及尿量作为急性肾损伤的标志物缺乏敏感性,延误了早期有效的治疗.近年来对于诊断急性肾损伤的生物学标志物方面的研究取得了较大进展,有些指标已逐步进入临床研究阶段,其中包括中性粒细胞明胶酶相关脂质运载蛋白、胱抑素C、肾损伤分子-1、白细胞介素-18等.本文旨在对心脏外科术后急性肾损伤早期生物学标志物基础及临床方面的研究进展作一综述.     

尿NGAL在儿童急性肾损伤诊断中的作用研究

目的：探讨尿中性粒细胞明胶酶相关脂质记载蛋白（neutrophil gelatinase-associate dlipocalin,NGAL）在儿童急性肾损伤诊断中的敏感性,特异性以及在鉴别肾前性氮质血症和急性肾损伤中的作用。方法：收集急性肾损伤的患儿36例,肾前性氮质血症患儿28例,正常对照组52例。所有入选患儿均常规测血压,检测血常规、肝功、肾功及离子、尿常规、尿钠、尿肌酐、尿NAG、尿α1-MG。每个入选患儿收集3～5ml尿液,离心后-80℃冰箱冻存,ELISA方法检测尿NGAL。结果：急性肾损伤组患儿尿NGAL值明显高于肾前性氮质血症组和正常对照组（399μg/g creatinine[SD,366];P〈0.01）。绘制ROC曲线后,NGAL在截断值为100μg/g creatinine时,其诊断儿童急性肾损伤的敏感性为0.91（CI：0.74～0.98）,特异性为0.98（CI0.97～0.99）;阳性似然比为155.33（CI56.34～464.75）,阴性似然比为0.08（CI0.03～0.27）,明显好于尿NAG,尿α1-MG和血肌酐。结论：尿NGAL在儿童急性肾损伤的诊断中,敏感性和特异性,阳性似然比和阴性似然比均明显好于血肌酐,并且可以在一定程度上鉴别肾前性氮质血症和急性肾损伤。     

Amelioration of cisplatin-induced acute kidney injury by recombinant neutrophil gelatinase-associated lipocalin

We investigated the protective effect and mechanism of neutrophil gelatinase-associated lipocalin (NGAL) in a murine model of cisplatin-induced nephrotoxicity. Male Swiss-Webster mice were assigned to four groups (n?=?10 in each group). Control mice received vehicle only. Mice in the experimental group were given a single intraperitoneal injection of cisplatin (20?mg/kg) to induce nephrotoxicity, and were divided into three groups. The first group received 100?μL of saline only via tail vein at the time of cisplatin administration. The second group was given biologically active recombinant NGAL via tail vein (250?μg/100?μL solution). The third group was injected with a 250?μg/100μL solution of inactivated NGAL. After 4 days, we measured serum creatinine and urinary N-acetyl-β-d-glucosaminidase (NAG), and performed histologic studies. Biologically active NGAL significantly blunted the rise in serum creatinine (NGAL plus cisplatin 1.33?±?0.31 versus cisplatin alone 2.43?±?0.31?mg/dL, p?<?.001) as well as the increase in urine NAG (NGAL plus cisplatin 60.7?±?14.2 versus cisplatin alone 120.5?±?22.5 units/gm creatinine, p?<?.005). In addition, NGAL conferred a marked reduction in tubule cell necrosis and apoptosis (NGAL plus cisplatin 6.9?±?1.2 versus cisplatin alone 15.1?±?3.4 TUNEL positive nuclei per 100 cells, p?<?.001). These beneficial effects were completely abolished when heat-inactivated NGAL was administered instead of the biologically active form. Since induction of NGAL in kidney tubules is a known physiologic response to cisplatin, the pharmacologic use of NGAL to prevent cisplatin nephrotoxicity is likely to be safe and effective.     

尿中性粒细胞明胶酶相关脂质运载蛋白在成人心脏手术后急性肾损伤早期诊断中的价值

目的 探讨尿中性粒细胞明胶酶相关脂质运载蛋白（neutrophil gelatinase-associated lipocalin,NGAL）在心脏手术后急性肾损伤（AKI）早期预测和诊断中的价值。 方法 前瞻性收集我院心脏手术患者手术前后不同时相的血、尿标本,选取其中14例AKI患者,分别测定尿NGAL和Scr水平;并选择临床资料相匹配的非AKI患者15例作为对照。观察两组患者围手术期尿NGAL和Scr的动态变化,运用接受者操作特性曲线（ROC）评价尿NGAL诊断AKI的精确性。AKI定义为Scr水平较基础值增加≥50%。 结果 Scr诊断AKI的中位时间为入ICU后24 h（10 h,48 h）。AKI患者术后入ICU即刻的尿NGAL水平显著高于术前基础水平并达峰值[20.51（13.42,50.02） μg/L比3.42（1.60,9.92） μg/L,P = 0.006];也显著高于非AKI患者 [2.91（0.72,8.61） μg/L,P = 0.002]。入ICU即刻尿NGAL 的ROC曲线下面积为0.824,95%的可信区间（CI）为0.667~0.980,P = 0.003。当以10.95 μg/L作为诊断截点时,此刻的尿NGAL在AKI诊断中的敏感性和特异性分别为85.7%和80.0%。入ICU即刻的尿NGAL与入ICU 24 h的Scr（r = 0.545,P = 0.002）及eGFR（r = －0.546,P = 0.002)呈正及负相关。 结论 心脏手术后AKI患者术后入ICU即刻的尿NGAL水平显著升高,对诊断AKI具有较高的准确性,其诊断AKI的时间早于Scr。尿NGAL可作为成人心脏术后AKI的早期诊断标志物。     

Urine neutrophil gelatinase-associated lipocalin levels predict acute kidney injury in acute decompensated heart failure patients

Abstract

Background: Acute heart failure (HF) syndromes are frequently complicated with cardiorenal syndromes. The aim of this study was to evaluate the performance of admission neutrophil gelatinase associated lipocalin (NGAL) levels to predict diuretic dose requirement and to predict the occurrence of acute kidney injury (AKI) in patients presenting with acute decompensated HF. Methods: Patients admitted with HF symptoms between December 2010 and October 2011 were prospectively enrolled. Samples were obtained for NGAL and brain natriuretic peptide. Patients were followed up until discharge or for three days, whichever happened first. They were grouped either to have AKI according to “Acute Kidney Injury Network” criteria or not (“no-AKI”). Results: One hundred patients were enrolled. Urine NGAL levels were higher in AKI group (median 31.3 vs. 16.2 ng/mL) (p?<?0.001). Oral furosemide using rates on admission was 60.5% in AKI group, 31.6% in no-AKI group. More AKI developed in patients using less furosemide orally on admission (p?=?0.023). Although the mean furosemide doses were similar on the first day (80?mg), diuretic dose increment was less on the following days in AKI group. Urine NGAL levels with 12?ng/mL cut-off value had sensitivity of 79% and specificity of 67% for predicting AKI. Multiple logistic regression analysis yielded an odds ratio of 10.9 for NGAL levels to predict AKI. Conclusion: Urine NGAL level in decompensated HF patients was not a significant predictor of diuretic dose requirement, but was a good marker for predicting AKI at 12?ng/mL cut-off value.     

尿液生物学标记物对肝移植患者术后急性肾损伤早期诊断的价值

目的 探讨尿液中乳酸脱氢酶(lactate dehydrogenase,LDH)、胱抑素C(cystatin C,Cys-C)、中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)对于肝移植患者术后急性肾损伤(acute kindey injury,AKI)早期诊断价值.方法 收集2011年1月～2011年10月在南方医院接受同种异体肝移植术的45例终末期肝病患者术前及手术结束时的静脉血液及尿液标本,检测血清肌酐( serum creatinine,SCr)、胱抑素、LDH及总胆红素,检测尿液中LDH、胱抑素、NGAL.根据AKI网络标准中的SCr标准将患者分为AKI组和非AKI组.比较两组术前、术后尿液中LDH、Cys-C、NGAL的变化情况,并运用受试者工作曲线(receiver operating characteristic curve,ROC)评价LDH、Cys-C、NGAL的准确性.结果 45例患者中20例发生了术后AKI,两组患者的年龄、性别、术前的基本情况、术中手术情况比较差异无统计学意义.AKI组和非AKI组术后血清SCr的差异具有统计学意义[(140±54)比(81±20),P＜0.05].术后AKI组及非AKI组尿液中的LDH、Cys-C、NGAL均升高,AKI组增加明显高于非AKI组.AKI组尿液中LDH、Cys-C、NGAL高于非AKI组,且差异具有统计学意义[(6.50±2.86)比(3.21±1.63),P＜0.05]、[(1.55±0.54)比(0.86±0.31),P＜0.05]、[(107±59)比(43±11),P＜0.05].ROC下面积结果显示,尿液中的LDH、Cys-C、NGAL均显示出了较好的诊断意义,面积分别为0.853、0.833、0.880,大于0.8. 结论 LDH、Cys-C、NGAL均表现出了较好的敏感性和特异性.     

Anemia-associated acute kidney injury after cardiac surgery with cardiopulmonary bypass

Objective To investigate the incidence and to evaluate the risk factors of acute kidney injury (AKI) following cardiac surgery with cardiopulmonary bypass (CPB) at general hospitals. Methods A retrospective cohort database study was conducted, involving 233 patients who were scheduled to heart valve surgery or coronary artery bypass grafting (CABG) with CPB technique. Logistic regression was used to screen out the risk factors of AKI after the surgery. Results The study population, with an average age of 57±12 years (age 21 to 83) were investigated, there were 54(23.2%) diabetes patients, 105 (45.1%) hypertension patients, 21 (9%) chronic kidney disease (CKD) patients, and 51 (21.9%) anemia patients. Overall incidence of AKI was 32.2%. The Analysis Result indicates that preoperative CKD, anemia, hypoalbuminemia, left ventricular ejection fraction, intraoperative aortic block time, minimum mean arterial pressure, perioperative infection, and application of vancomycin are risk factors associated with postoperative AKI. Multiariable Logistic regression suggests that basic CKD (OR=9.498, P=0.001), anemia (OR=3.150, P=0.021), the LVEF before surgery (OR=1.733, P=0.045), intraoperative aortic block time (OR=2.227, P=0.026), and white blood cell (OR=3.357, P=0.032) were the independent risk factors of AKI. Conclusions AKI is a common complication following cardiac surgery with CPB. The patients with preoperative renal insufficiency, anemia, long intraoperative aortic block time and higher perioperative white blood cell count are subjected to a higher incidence of AKI. Alleviating patients’ anemia and reducing artery block of extracorporeal circulation time therefore might be potential means to mitigate the risks of AKI after cardiac surgery.     

尿NGAL在2型糖尿病肾病肾小管间质损伤评价中的价值

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)、eGFR]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eGFR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。     

Neutrophil gelatinase-associated lipocalin worsens ischemia/reperfusion damage of kidney cells by autophagy

This study aimed to explore the influence of neutrophil gelatinase-associated lipocalin on autophagy and its role in ischemia/reperfusion injury in human kidney-2 (HK-2) cells during acute kidney injury (AKI). HK-2 cells were given hypoxia/reoxygenation treatment for different times to simulate ischemia/reperfusion injury. Autophagy was evaluated by western blot and immunofluorescence of GFP-LC3. Cell viability was tested to reflect the degree of cell damage. The autophagy inhibitor 3-MA was used to inhibit autophagy and determine the role of autophagy in ischemia/reperfusion injury. HK-2 cells were hypoxia for 1?h, followed by reoxygenation treatment for 24?h. These cells were then exposed to human recombinant protein neutrophil gelatinase-associated lipocalin (NGAL) (50, 100, 200, 400, or 1000?ng/mL) with or without 3-MA. Our results showed that autophagy was induced by hypoxia treatment and was further enhanced by reoxygenation after hypoxia treatment. Cell viability was decreased with the inhibition of autophagy in the process. Autophagic flux was further induced with NGAL (>200?ng/mL), while cell viability declined in this condition. Cell viability was recovered when autophagy was inhibited. These results indicate that autophagy plays, in part, a protective role in renal ischemia/reperfusion injury. Furthermore, the data suggest that NGAL strengthens the level of autophagy in this process. Overall, a large quantity of NGAL produced by renal proximal tubular epithelial cells may induce excessive autophagy and increase renal ischemia/reperfusion injury in acute kidney injury.