联合应用标志物在心脏手术后急性肾损伤的早期诊断

目的 探讨血清胱抑素C（CyC）、尿中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、白细胞介素18（IL-18）、视黄醇结合蛋白（RBP）、N-乙酰-β-D-氨基葡萄糖苷酶（NAG）在成人心脏手术后急性肾损伤（AKI）早期预测和诊断中的价值及其联合应用的价值。 方法 前瞻性收集心脏手术患者手术前后不同时相的血尿标本,选取其中AKI患者14例,分别测定血清CyC、Scr及尿NGAL、IL-18、RBP、NAG、Cr（Ucr）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上述5种生物学标志与Scr的动态变化。用受试者工作特征（ROC）曲线及曲线下面积（AUC）评价标志物的单独或联合应用时诊断AKI的精确性。AKI定义为Scr水平较基础值增加≥50%。 结果 29例患者平均年龄（62.9±13.7）岁,基础Scr （73.2±11.9） μmol/L。除AKI组患者术中升主动脉阻断时间较非AKI组较长外[（60.63±13.92） min比（43.00±9.20） min,P=0.047],两组其余临床指标差异均无统计学意义。AKI组患者的血尿生物学标志分别在术后早期的不同时间点显著升高。术后10 h血CyC取1.31 mg/L作为诊断截点时,其在AKI诊断中的敏感性（ST）和特异性（SP）分别为0.71和0.92,AUC=0.83（0.67~1.00）;术后0 h 尿NGAL取49.15 μg/g Ucr时,ST=0.84,SP=0.80,AUC=0.85（0.70~1.00）。术后2 h尿IL-18取285.65 ng/g Ucr时,ST=0.85,SP=0.73,AUC=0.81（0.64~0.97）。术后0 h尿RBP取2934.65 μg/g Ucr时,ST=0.75,SP=0.67,AUC=0.77（0.60~0.95）。术后4 h尿NAG取37.05 U/mg Ucr时,ST=0.86,SP=0.67,AUC=0.72（0.53~0.92）。利用Logistic回归方程,联合以上5种标志物的最佳诊断时间点,得到AUC为0.98（0.93~1.02）（P<0.01）。 结论 心脏手术后AKI患者血尿生物学标志在术后不同时间点显著升高,诊断AKI的时间早于Scr,具有较高的准确性,可作为成人心脏手术后AKI的早期诊断标志物。尿NGAL的ROC曲线下面积最大,尿RBP也显示了较好的诊断价值。联合应用生物学标志可更好地预测临床上AKI的发生。     

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。     

尿中性粒细胞明胶酶相关载脂蛋白和肝型脂肪酸结合蛋白对肝移植术后急性肾损伤的早期诊断价值

目的 探讨尿中性粒细胞明胶酶相关载脂蛋白（NGAL）和肝型脂肪酸结合蛋白（L-FABP）在肝移植术后急性肾损伤（AKI）中的早期诊断价值。 方法 前瞻性收集2007至2008年间25例肝移植患者术前、门静脉开放后2、4、6、12、24、48、72和120 h的血液和尿液标本,检测Scr和尿NGAL及L-FABP水平。根据急性肾损伤网（AKIN）标准中的Scr标准将患者分为AKI组和非AKI组。观察两组各时间点尿NGAL、尿L-FABP和Scr水平的动态变化;运用受试者工作特征曲线（ROC）评价尿NGAL和L-FABP诊断AKI的精确性。 结果 25例患者中11例发生了术后AKI,两组患者术前、术中及术后情况差异无统计学意义。术后24 h AKI组与非AKI组的Scr差异有统计学意义[(90.48±50.32) 比（59.84±14.72） μmol/L,P < 0.05]。AKI组与非AKI组术后2～120 h尿L-FABP均显著升高,4 h时差异有统计学意义[2361.41（1036.89~4048.93） ng/mgCr比5246.97（2406.33~7688.21） ng/mgCr,P < 0.05]。AKI组术后2、4、6 h尿NGAL均显著高于非AKI组,差异有统计学意义 [69.02（29.79~237.29）比22.94（8.69~46.23） ng/mgCr,29.34（16.06~536.91）比 12.66（8.91~22.78） ng/mgCr和34.23（11.47~81.26）比11.84（6.57~20.10） ng/mgCr,均P < 0.05]。ROC曲线下面积（AUC）结果显示,与尿L-FABP相比（当4 h截断点为3451.75 ng/mgCr时,AUC为0.760）,尿NGAL对早期诊断AKI具有更高的敏感性和特异性（2、4、6 h的截断点分别为43.02、26.97和17.19 ng/mgCr时,AUC分别为0.766、0.773和0.773）。 结论 尿NGAL在肝移植术后早期AKI的诊断上表现出较高的敏感性和特异性,也许能作为肝移植术后AKI早期诊断的生物学标志物,但仍需要大样本的临床研究加以证实。     

尿肝型脂肪酸结合蛋白及其与尿中性粒细胞明胶酶相关脂质运载蛋白联合应用在成人心脏手术后急性肾损伤诊断中的作用

目的 探讨尿肝型脂肪酸结合蛋白( L-FABP)及其与尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)联合应用在预测成人心脏手术后急性肾损伤(AKI)的发生及严重程度中的价值,以期能为临床AKI的早期诊断提供方便可靠的方法.方法 前瞻性收集心脏手术患者术前、术后即刻及术后2h的血和尿标本,分别检测Scr、尿L-FABP和NGAL水平,比较AKI和非AKI患者术后各标志物的动态变化情况.运用受试者工作特征(ROC)曲线及曲线下面积(AUC)评估标志物单独及联合应用时诊断AKI的准确性.结果 总共109例患者中26例(23.9％)发生了AKI,其中AKIN Ⅰ、Ⅱ和Ⅲ期分别占46.2％ 、34.6％和19.2％.尿L-FABP 和NGAL水平在AKI组术后即刻及术后2h均显著高于非AKI组,其浓度变化明显早于Scr.两时间点各标志物单独预测AKI的发生及Ⅱ和Ⅲ期AKI的AUC均在0.81～0.87.用Logistic 回归方程联合术后同一时间点的尿NGAL和尿L-FABP,则术后即刻和术后2h预测术后AKI 及严重程度的精确性进一步提高( AUC=0.911～0.927).结论 尿L-FABP和尿NGAL在心脏术后AKI早期即显著升高,比Scr能更早地预测AKI的发生和严重程度,两者联合应用则可使诊断的精确性进一步提高.     

尿热休克蛋白-70在体外循环术后急性肾损伤早期诊断中的价值

目的评估尿热休克蛋白(HSP)-70在心脏体外循环心肺转流术(CPB)后急性肾损伤(AKI)早期诊断中的价值。方法选取2018年5月至2018年7月在河南省人民医院接受CPB治疗的患者为研究对象。收集入选者术前及术后0、2、4、6、8、12、24、48 h尿液标本和临床资料。按照肾脏病改善全球预后组织(KDIGO)AKI诊断标准分为AKI组和非AKI组。酶联免疫吸附法测定尿HSP-70、金属蛋白酶组织抑制因子2(TIMP-2)和胰岛素样生长因子结合蛋白7(IGFBP7)水平;免疫比浊法测定尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平。绘制受试者工作特征曲线(ROC),计算尿HSP-70、[TIMP-2]×[IGFBP7]、NGAL诊断CPB术后发生AKI的临界值、敏感度及特异度。结果共纳入45例患者,其中AKI组24例,非AKI组21例。AKI组术后各时间点尿HSP-70、[TIMP-2]×[IGFBP7]和NGAL水平显著高于非AKI组,组间比较差异有统计学意义(均P<0.05)。AKI组尿HSP-70在CPB术后2 h达到峰值,明显早于尿[TIMP-2]×[IGFBP7]、尿NGAL达峰值时间(分别为术后12 h和术后4 h)。术后2 h尿HSP-70≥2.1μg/L预测CPB术后AKI的曲线下面积(AUC)=1.00,灵敏度为100.0%,特异度100.0%;术后12 h尿[TIMP-2]×[IGFBP7]>19.1μg2/L2预测CPB术后AKI的AUC=0.94,灵敏度87.5%,特异度100.0%;术后4 h尿NGAL>27.4μg/L预测CPB术后AKI的AUC=0.95,灵敏度95.8%,特异度85.7%。术后2 h尿HSP-70≥2.1μg/L预测CPB术后AKI的阳性预测值为100.0%,阴性预测值100.0%。结论CPB术后AKI患者尿HSP-70水平升高早于尿[TIMP-2]×[IGFBP7]、NGAL,尿HSP-70水平监测有助于AKI的早期发现。     

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。     

白细胞介素-18早期诊断冠脉搭桥术后急性肾损伤的研究

目的 研究白细胞介素-18 (IL-18)与冠脉搭桥手术后急性肾损伤(AKI)的关系.方法 选择冠状动脉硬化性心脏病行冠脉搭桥手术的患者80例,根据AKI诊断标准,分为AKI组和非AKI组.分别留取术前及术后2、4、6、8、12、24 h等不同时间点的血液和尿液标本,测定标本中血清肌酐(Scr)、血液及尿液中IL-18水平.运用ROC曲线及曲线下面积评价尿液及血液的IL-18对AKI的敏感性及特异性.结果 80例患者共有13例发生AKI,发病率为16.25％,AKI组Scr升高峰值出现在24 ～ 48 h内.血、尿IL-18峰值均出现在术后4h,ROC曲线显示术后2h血及尿IL-18的AUC均＞0.8.Logistic回归分析表明术后2h血、尿IL-18是冠脉搭桥手术后AKI发生的有效预测指标.结论 冠脉搭桥手术后血液及尿液IL-18可作为冠脉搭桥术后AKI早期诊断生物标志物.     

急性肾损伤患者尿液IL-18、NGAL的变化

目的:探讨急性肾损伤(AKI)患者尿液中白细胞介素-18(IL-18)、中性粒细胞明胶酶相关脂蛋白(NGAL)的改变及临床意义。方法:AKI患者30例,原发性慢性肾脏病(CKD)患者30例,健康对照者30例,应用酶联免疫吸附检测法(ELISA)测定三组患者尿液IL-18、NGAL水平的变化;测定三组血清肌酐值。结果:血清肌酐AKI组较CKD组及健康对照组增高(P<0.001),而CKD组与健康对照组比较差异无统计学意义(P>0.05)。AKI组尿IL-18水平高于CKD组(P<0.05),显著高于健康对照组(P<0.001)。CKD组尿IL-18水平高于健康对照组,但差异无统计学意义(P>0.05)。AKI组尿NGAL水平高于CKD组(P<0.05),显著高于健康对照组(P<0.001);CKD组尿NGAL水平高于健康对照组,但差异无统计学意义(P>0.05)。尿IL-18与尿NGAL之间存在正相关关系(r=0.994)。结论:尿IL-18、NGAL在急性肾损伤患者中均增高,是反映AKI较敏感的生物学标志物。     

乌司他丁对脓毒症致大鼠急性肾损伤肾功能及尿相关指标的影响

目的探讨乌司他丁（UTI）对盲肠结扎穿孔术（CLP〉所致大鼠脓毒症急性肾损伤（AKI）的保护作用。方法SD健康雄性大鼠55只,按随机化原则分成3组：正常对照组5只、模型组25只、乌司他丁治疗组25只,后两组再随机分为5个时间点（1h、6h、12h、24h、48h）,每组每时间点各5只,采用盲肠结扎穿孔术复制脓毒症模型,乌司他丁治疗组,造模后立即给予乌司他丁10万U／kg,尾静脉注射,分别在各个时间点采血、留尿标本,进行肾功能血肌酐（Scr）、尿素（Urea）,尿肾损伤分子（KIM-1）、白细胞介素-18（IL-18）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）检测分析。结果与模型组相比,乌司他丁治疗组大鼠各时间点Scr、Urea,尿KIM-1、IL-18、NGAL浓度均显著降低,差异均有统计学意义（P〈0．05）。结论乌司他丁对脓毒症所致急性肾损伤具有一定的肾脏保护作用。     

尿液中性粒细胞明胶酶相关脂质运载蛋白和白细胞介素18水平检测在移植肾功能延迟恢复早期预测中的应用价值

目的 评价尿液中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和白细胞介素18(IL-18)水平检测在早期预测移植肾功能延迟恢复(DGF)中的价值.方法 采用ELISA法,连续监测86例肾移植患者术前和术后12、24 h尿液标本中NGAL,IL-18及视黄醇结合蛋白(RBP)水平,并分析其与DGF的关系. 结果 86例中发生DGF 15例.术后12 h DGF组尿NGAL(ng/mg)水平明显高于非DGF组(1712.7±474.6比863.1±199.8,P<0.001),尿IL-18(ng/mg)水平与非DGF组比较差异无统计学意义(29.2±4.1比28.7±4.2,P>0.05);术后24 h DGF组尿NGAL和IL-18水平均明显高于非DGF组(分别为2905.0±1108.1比911.8±221.0,211.3±34.0比86.9±22.8,均P<0.001);而尿RBP(μg/mmol)(92.7±17.1比92.8±13.8,P>0.05)和SCr值(μmol/L)(608.1±85.5比542.3±99.6,P>0.05)与非DGF组比较差异无统计学意义.ROC曲线下面积分析结果显示,术后12 h尿NGAL曲线下面积为0.90,cut-off值为996.5 ng/mg时,诊断敏感性90.2%,特异性82.6%;术后24 h IL-18曲线下面积为0.76,cut-off值为148.5 ng/mg时,诊断敏感性76.3%,特异性66.4%. 结论 尿NGAL及IL-18水平变化对早期预测DGF发生有重要的临床意义.     

Urine Neutrophil Gelatinase-Associated Lipocalin and Interleukin-18 Predict Acute Kidney Injury after Cardiac Surgery

Background. About 30–50% patients develop acute kidney injury (AKI) after cardiac surgery, which is still diagnosed by serum creatinine on clinic. However, the increase of serum creatinine is insensitive and delayed. The aim of this study is to test the hypothesis that neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) are early biomarkers for AKI in patients after cardiac surgery. Methods. Thirty-three cases undergoing cardiac surgery were classified into an AKI group and non-AKI group, according to the AKI definition (> 26.5 μmol/L increase of serum creatinine, more than or equal to 50% increase of serum creatinine within 48 h, or a reduction in urine output < 0.5 mL/Kg per hour for more than six hours). The concentrations of serum NGAL, urine NGAL, and urine IL-18 at different time-points were measured. Results. Nine cases (27.27%) developed postoperative AKI, but diagnosis with serum creatinine was 12–48 h postoperation. The concentrations of serum NGAL were not significantly increased postoperation. The concentrations of urine NGAL and IL-18 were significantly increased in the AKI group, which reached the peak at 2–4 h postoperation, and a more significant difference could be seen after correction for urine creatinine. The concentrations of urine NGAL and IL-18 2 h postoperation, either corrected for urine creatinine or not, showed good sensitivity and specificity. Increased levels of urine NGAL and IL-18 2 h postoperation were significantly correlated with increased level of serum creatinine 12 h postoperation. Logistic regression analysis showed that urine NGAL corrected for urine creatinine 2 h postoperation and urine IL-18 2 h postoperation emerged as powerful independent predictors of AKI after cardiac surgery. Conclusions. The concentrations of urine NGAL and IL-18 could be useful biomarkers for AKI in patients after cardiac surgery, especially after correction for urine creatinine.     

Prediction of acute kidney injury complicated by sepsis with sTREM - 1 and NGAL as early marker

Objective To determine whether triggering receptor expressed on myeloid cells-1 (sTREM - 1) and urinary neutrophil gelatinase - associated lipocalin (NGAL) were early biomarkers of acute kidney injury (AKI) secondary to sepsis. Methods A total of 141 eligible patients were enrolled in this prospective study. Blood and urine samples were collected at different time points as soon as sepsis was diagnosed. The concentrations of serum creatinine (Scr), urine sTREM-1 and NGAL were measured. According to AKI criteria, patients were divided into the AKI group and non - AKI group. Dynamic changes of levels of Scr, urine sTREM-1 and NGAL were observed in two groups. The receiver operating characteristic curves were used to evaluate the early diagnostic value of urine sTREM-1 and NGAL. Results Among 141 septic patients, 44 (31.2%) cases had concomitant AKI. Twenty four hours after sepsis diagnosed, the level of Scr rose to 1.91 times of the baseline [(140.5±13.6) vs (82.6±15.3) μmol/L, P＜0.05], which met the diagnostic criteria of AKI. In the AKI group, urinary concentrations of sTREM-1 and NGAL at 8 h after the diagnosis of sepsis began to rise significantly from baseline [(100.5±17.4) vs (38.9±14.7) ng/L; (144.6±51.9) vs (56.2±43.8) μg/L, both P＜0.05].And at the following time points, urinary concentrations of sTREM - 1 and NGAL were significantly higher than the baseline levels and that of the non-AKI group (all P＜0.05). At 8 h time point, the area under the curve of urine sTREM-1 was 0.877 (95%CI 0.756-0.914), the sensitivity was 89.1% and specificity was 82.0% with a cutoff value of 70 ng/L. At 8 h time point, the area under the curve of urine NGAL was 0.862 (95% CI 0.703-0.958),the sensitivity was 87.4% and specificity was 85.5% with a cutoff value of 90 μg/L. Conclusions Urinary concentrations of sTREM-1 and NGAL at 8 h time point after the diagnosis of sepsis have predictive value for AKI and their diagnostic time is much earlier than that of Scr. Therefore, urinary sTREM-1 and NGAL can be used as early biomarkers of septic AKI.     

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis

PurposeTo investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis.MethodsA retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI.ResultsThe level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p < 0.01). The ROC analysis showed the combined detection of urine IL-8, NGAL and KIM-1 at 12 h had a larger area under curve (AUC) than a single marker (0.997, 95% CI: 0.991–0.998), and the sensitivity and specificity were 98.2% and 96.7%, respectively. Pearson correlation analysis showed that the levels of urine NGAL at 4, 12, 24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18 (p < 0.01).ConclusionAKI could be quickly recognized by the elevated level of urine IL-8, NGAL and KIM-1 in patients with URL-related urosepsis. Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance, which may be an important reference for the early diagnosis of AKI.     

Neutrophil gelatinase associated lipocalin as an indicator of acute kidney injury and inflammation in burned children

Introduction

Neutrophil gelatinase associated lipocalin (NGAL) is a novel predictor of acute kidney injury (AKI), which increases with inflammation. We aimed to assess whether serum NGAL (SNGAL) and urine NGAL (UNGAL) can predict AKI in burned children.

Methods

Patients were referred within the 12 h of burn to our center. Serum samples for SNGAL, C-reactive protein (CRP), procalcitonin (PCT) and urine for UNGAL, microalbumine (Umalb), creatinine (Ucr) were obtained at both admission and the 5th day after burn. Blood urea nitrogen (BUN) and serum creatinine (Scr) were examined daily.

Results

Twenty-two subjects were enrolled and six (27.2%) of them developed AKI within the 48 h of injury. Burn size and abbreviated burn severity index (ABSI) were significantly increased in patients with AKI. CRP, PCT, SNGAL and UNGAL levels at admission and day 5 were significantly higher in patients with AKI than in those without AKI and controls. Scr was not significant between AKI and non-AKI groups at hospital days 1 and 5. A SNGAL level of 315 ng/ml and a UNGAL level of 100 ng/ml were determined as predictive cut-off values of AKI at admission (sensitivity and specificity: 71.4%, 83.3% and 93.3%, 93.7%, respectively). SNGAL and UNGAL were positively correlated with CRP, PCT, ABSI and Umalb/Ucr.

Conclusion

SNGAL and UNGAL are good early predictors of AKI in children with severe burn. NGAL might reflect the severity of burn insult and also could be used as an indicator of inflammation in burn children.