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.     

Klotho protein as a biomarker for the detection and prognosis of acute kidney injury among adult patients in the intensive care units

Objective To evaluate the clinical significance of serum Klotho protein levels in the early diagnosis and prognosis of acute kidney injury (AKI) among adult patients in the intensive care units (ICU). Methods The study was prospective and observational. Blood samples and clinical data of AKI patients admitted to the ICU of the First Affiliated Hospital of Xinjiang Medical University between July 1 and August 31, 2016 were collected. ELISA was used for the detection of Klotho and NGAL. Receiver operating characteristic curve (ROC) and the area under the curve (AUC) were used to compare the predictive performance among Klotho, NGAL and serum creatinine, evaluating the sensitivity and specificity of Klotho on the diagnosis of AKI. The correlation between Klotho and prognosis of AKI was investigated by comparing serum Klotho levels and early AKI predictors. Results The patients were divided into AKI group of 52 cases and non-AKI group of 98 cases. The baseline serum Klotho level in AKI group was significantly lower than that in non-AKI group (P＜0.001). The AUC of Klotho predicting for AKI was 0.945(95% CI: 0.892-0.997) and the best cut off value was 1.76 μg/L(sensitivity 92%, specificity 94%). The predictive ability of Klotho was significantly higher than serum creatinine (Scr), and the sensitivity is higher than NGAL (sensitivity 87%, specificity 96%). Serum Klotho combined with Scr predicted better AKI (AUC=0.958, 95% CI: 0.915-1.000, sensitivity 96%, sensitivity 92%). The level of Klotho in patients with AKI was significantly different between the renal function recovery group and non-recovery group (P=0.047), while there was no significant difference between the two groups in the level of NGAL and Scr (P＞0.05). There was no significant correlation between the Klotho level at diagnosis of AKI and peak Scr, peak eGFR, Scr at discharge and eGFR at discharge (r=0.026, P=0.853; r=-0.127, P=0.368; r=0.243, P=0.082; r=-0.187, P=0.184). Conclusion Serum Klotho may be a potential biomarker for early diagnosis of AKI, but the association between serum klotho and the prognosis of AKI requires further study.     

尿生物标志物在儿童急性肾损伤早期诊断中的作用研究

目的：评价尿NGAL,KIM-1和β2-MG在儿童不同基础疾病导致的AKI早期诊断中的价值。方法：我们做的是前瞻性临床研究,检测在我院儿科门急诊不同疾病患儿尿中性粒细胞明胶酶相关的脂质运载蛋白（NGAL）,肾脏损伤因子-1（KIM-1）和-β2微球蛋白（β2-MG）的水平,以AKIpRIFLE为分期标准将入选患儿分组,比较尿NGAL,KIM-1和β2-MG在儿童急性肾损伤诊断中的敏感性,特异性,阳性似然比,阴性似然比,分析比较这3个指标在急性肾损伤早期诊断中的作用。结果：入选262例患儿中,23例患儿可诊断为AKI,15例患儿为AKI-R期,8例患儿为AKI-I期,入选患儿中没有AKI-F期,23例患儿中只有5例临床有AKI的诊断。尿NGAL,KIM-1和β2-MG的水平在血肌酐没有明显升高之前已经升高,随着肾损伤的加重升高的更明显,不同组间差异有统计学意义。尿NGAL和β2-MG在预测儿童AKI的早期诊断方面好于尿KIM-1（AUC〉0.8）。结论：尿NGAL,KIM-1和β2-MG均可以在Scr没有升高之前预测儿童AKI的发生,是儿童AKI的早期生物标志物。尿NGAL在早期预测不同基础疾病可能发生AKI方面好于其他两项指标。     

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。     

心脏术后尿中性粒细胞明胶酶相关脂质运载蛋白和白细胞介素18与急性肾损伤的关系

目的 探讨接受体外循环心脏手术患者尿中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和尿白细胞介素18（IL-18）与急性肾损伤（AKI）的关系。 方法 根据AKI的诊断标准，将33例体外循环心脏手术的患者分为AKI组及非AKI组，分别留取术前及术后不同时间点的血液和尿液标本，测定Scr、尿NGAL和IL-18水平。 结果 33例中有9例发生AKI，发生率为27.27%。AKI组Scr升高峰值出现在12～48 h内。与术前相比， AKI组术后2 h、4 h尿NGAL及IL-18水平升高，差异有统计学意义（P < 0.01）。与非AKI组比较，AKI组术后各时间点的尿NGAL水平、术后2 h及4 h的尿IL-18水平都较高，差异有统计学意义（P < 0.01）。经尿肌酐（Ucr）校正后，相应时间点的NGAL/Ucr和IL-18/Ucr差异仍有统计学意义（P < 0.01）。术后2 h尿NGAL和尿NGAL/Ucr的界定（cutoff） 值分别在250 µg/L和250 µg/mmol时；术后2 h尿IL-18和尿IL-18/Ucr的界定值分别在1800 ng/L和1800 ng/mmol时，体现出较好的敏感性和特异性。 AKI组术后12 h Scr水平与术后2 h尿NGAL水平呈正相关（r = 0.638，P < 0.05）。结论 体外循环下接受心脏手术的患者AKI发生率较高；术后2 h尿NGAL和NGAL/Ucr、术后2 h尿IL-18和尿IL-18/Ucr当达到一定界定值时，均可作为体外循环下心脏手术后AKI发生的早期诊断参考指标，其中术后2 h尿NGAL/Ucr为250 µg/mmol时更敏感。     

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。     

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.     

Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function

To better understand the diagnostic and predictive performance of urinary biomarkers of kidney injury, we evaluated γ-glutamyltranspeptidase (GGT), alkaline phosphatase (AP), neutrophil-gelatinase-associated lipocalin (NGAL), cystatin C (CysC), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in a prospective observational study of 529 patients in 2 general intensive care units (ICUs). Comparisons were made using the area under the receiver operator characteristic curve (AUC) for diagnosis or prediction of acute kidney injury (AKI), dialysis, or death, and reassessed after patient stratification by baseline renal function (estimated glomerular filtration rate, eGFR) and time after renal insult. On ICU entry, no biomarker had an AUC above 0.7 in the diagnosis or prediction of AKI. Several biomarkers (NGAL, CysC, and IL-18) predicted dialysis (AUC over 0.7), and all except KIM-1 predicted death at 7 days (AUC between 0.61 and 0.69). Performance was improved by stratification for eGFR or time or both. With eGFR <60?ml/min, CysC and KIM-1 had AUCs of 0.69 and 0.73, respectively, within 6?h of injury, and between 12 and 36?h, CysC (0.88), NGAL (0.85), and IL-18 (0.94) had utility. With eGFR >60?ml/min, GGT (0.73), CysC (0.68), and NGAL (0.68) had the highest AUCs within 6?h of injury, and between 6 and 12?h, all AUCs except AP were between 0.68 and 0.78. Beyond 12?h, NGAL (0.71) and KIM-1 (0.66) performed best. Thus, the duration of injury and baseline renal function should be considered in evaluating biomarker performance to diagnose AKI.     

重症感染合并急性肾损伤中NGAL的变化

目的探讨尿中性粒细胞明胶酶相关载脂蛋白在重症感染合并急性。肾损伤中的诊断价值。方法选择2010年1月--2011年6月在新疆自治区人民医院ICU住院的重症感染患者79例,按急性肾损伤的诊断标准分为急性肾损伤组和非急性肾损伤组。分别测定尿中性粒细胞明胶酶相关载脂蛋白、N-乙酰-β-D-氨基葡萄糖苷酶、微量白蛋白和血肌酐的浓度。通过受试者工作特征曲线及曲线下面积评价各项指标的敏感性。结果急性肾损伤组中各项指标的测定浓度明显高于非急性肾损伤组,其中尿中性粒细胞明胶酶相关载脂蛋白的敏感性和特异性分别为0．95和0．90,曲线下面积=0．986（0．9681．004）;血肌酐的敏感性和特异性分别为0．75和0．69,曲线下面积=0．776（0．705～0．852）,差异具有统计学意义（P〈0．001）。结论’尿中性粒细胞明胶酶相关载脂蛋白的敏感性高于血肌酐,可以作为重症感染合并急性肾损伤的早期诊断标记物。     

KIM-1、CC16在急性肾/肺损伤临床诊断中的意义

目的观察肾损伤分子-1（kidney injury molecule 1, KIM-1）与Clara细胞分泌蛋白（Clara cell secretion protein, CCSP/CC16）在急性肾损伤（Acute Kidney Injury, AKI）合并急性肺损伤（Acute Lung Injury, ALI）患者体内的变化,探讨其在急性肾/肺损伤临床诊断中的意义。方法入选本院确诊为AKI的患者纳入AKI组（25例）,确诊为ALI的患者纳入ALI组（15例）,确诊为AKI合并ALI的患者纳入AKI+ALI组（25例）,与之年龄、性别、民族相匹配的非吸烟健康志愿者作为正常对照组（23例）,采用酶联免疫吸附法(enzyme-linked immunosorbent assay, ELISA)检测尿液KIM-1、尿液CC16和血浆KIM-1、血浆CC16的水平,用比色法检测尿N-乙酰-β-D-氨基葡萄糖苷酶(N-acetyl-beta-D-glucosaminidase, NAG),整理四组所有研究资料利用统计学方法进行综合分析。 结果与正常非吸烟对照组相比,AKI组的尿NAG酶、尿KIM-1、血浆KIM-1和血浆CC16水平均显著升高,差异有统计学意义（P＜0.05）;ALI组的尿CC16和血浆CC16水平均显著升高,差异有统计学意义（P＜0.05）;AKI+ALI组的尿NAG酶、尿KIM-1、血浆KIM-1、尿CC16和血浆CC16水平均显著升高,差异有统计学意义（P＜0.05）。 直线相关分析显示：AKI患者的尿KIM-1水平与尿NAG呈显著正相关关系（r=0.493, P＜0.01）,血浆KIM-1水平与尿NAG无直线相关关系（r=0.276, P＞0.05）。ALI患者的尿CC16、血浆CC16与氧合指数均呈显著负相关关系(r=0.460, P＜0.01; r=0.468, P＜0.01)。AKI合并ALI患者的尿KIM-1、血浆KIM-1与尿CC16、血浆CC16均呈显著正相关关系（P＜0.05）。3. ROC曲线分析提示：在AKI诊断中,尿KIM-1曲线下面积为0.781（95% CI：0.688～0.875,P＜0.01）;血浆KIM-1曲线下面积为0.988（95% CI：0.000～1.000,P＜0.01）;尿NAG酶曲线下面积为0.798（95% CI：0.708～0.888,P＜0.01）。在ALI诊断中,尿CC16曲线下面积为1.000(95% CI：1.000～1.000,P＜0.01);血浆CC16曲线面积为0.849（95% CI：0.764～0.935,P＜0.01）。 结论 AKI时尿NAG、尿KIM-1、血浆KIM-1均明显升高,进一步证实这些指标可作为诊断AKI早期生物学标志物。2. ALI时尿CC16、血浆CC16水平显著升高,同时具有高敏感性,是诊断ALI的良好实验室指标。急性肾/肺损伤患者体内尿、血浆KIM-1与CC16水平明显升高,二者具有良好的相关性,对诊断急性肾/肺损伤并判断预后具有重要的价值与临床意义。     

Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes

In established acute kidney injury (AKI), serum creatinine poorly differentiates prerenal from intrinsic AKI. In this study, we tested whether urinary neutrophil gelatinase-associated lipocalin (NGAL) distinguishes between intrinsic and prerenal AKI, and tested its performance in predicting a composite outcome that included progression to a higher RIFLE (Risk, Injury, Failure, Loss of function, End stage renal disease) class, dialysis, or death. Urinary NGAL was measured using a standardized clinical platform in 161 hospitalized patients with established AKI. Sixteen patients were excluded because of postrenal obstruction or insufficient clinical information. Of the remaining 145 patients, 75 had intrinsic AKI, 32 had prerenal AKI, and 38 patients could not be classified. Urinary NGAL levels effectively discriminated between intrinsic and prerenal AKI (area under the receiver-operating characteristic curve 0.87). An NGAL level over 104?μg/l indicated intrinsic AKI (likelihood ratio 5.97), whereas an NGAL level <47?μg/l made intrinsic AKI unlikely (likelihood ratio 0.2). Patients experiencing the composite outcome had significantly higher median urinary NGAL levels on inclusion. In logistic regression analysis, NGAL independently predicted the composite outcome when corrected for demographics, comorbidities, creatinine, and RIFLE class. Hence, urinary NGAL is useful in classifying and stratifying patients with established AKI.     

Efficacy of urinary midkine as a biomarker in patients with acute kidney injury

Background

The mortality and morbidity associated with acute kidney injury (AKI) remains high, despite advances in interventions. A multifunctional heparin-binding growth factor, midkine (MK), is involved in the pathogenesis of ischemic kidney injury. However, the clinical relevance of MK has not yet been elucidated. The present study investigated whether urinary MK can serve as a novel biomarker of AKI.

Methods

We initially compared the predictive value of MK with other urinary biomarkers, including N-acetyl-β-d-glucosaminidase (NAG), interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin (NGAL), for the detection and differential diagnosis of established AKI (549 patients). Subsequently, the reliability of MK for the early detection of AKI was prospectively evaluated in 40 patients undergoing elective abdominal aortic aneurysm surgery. Urine samples were obtained at baseline, the period of aortic cross-clamping and declamping, the end of the surgery, and on post-operative day 1.

Results

The areas under the receiver operating characteristic curves for the diagnosis of AKI in various kidney diseases were 0.88, 0.70, 0.72, and 0.84 for MK, NAG, IL-18, and NGAL, respectively. When the optimal cutoff value of urinary MK was set at 11.5 pg/mL, the sensitivity and specificity were 0.87 and 0.85, respectively. In the second study, urinary MK peaked at the period of aortic declamping, about 1 h after cross-clamping in patients with AKI. Interestingly, the rise of MK in AKI patients was very precipitous compared with other biomarker candidates.

Conclusion

Urinary MK was prominent in its ability to detect AKI and may allow the start of preemptive medication.

     

Value of urinary L-FABP and NGAL in the diagnosis of acute kidney injury caused by obstructive nephropathy and the prediction of renal outcome

Objective To evaluate the values of urinary liver-fatty acid binding protein (uL-FABP) and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in diagnosis of acute kidney injury (AKI) caused by obstructive nephropathy and in the prediction of renal prognosis. Methods Clinical data of 30 patients with obstructive nephropathy were collected prospectively. uL-FABP and uNGAL were measured by ELISA at various time points. Risk factors of the renal outcome were evaluated. The patients were followed up for at least one year. Results Patients with AKI had higher levels of uL-FABP and uNGAL compared to those without AKI [700.00(154.62-1216.14) μg/g•Cr vs 26.90 (16.77-41.38) μg/g•Cr; 1266.69 (671.57-3396.07) μg/g•Cr vs 179.12 (90.98-215.16) μg/g•Cr, all P＜0.01]. Positive correlations of uL-FABP and uNGAL with serum creatinine were found (r＝0.552, 0.553, all P＜0.01). The AUCs of uL-FABP and uNGAL to detect AKI were 0.925 and 0.900. Patients with non complete renal recovery had higher levels of uL-FABP before operation and 72-hour after operation compared to those with complete renal recovery (all P＜0.01). Before operation, the AUC of uL-FABP to detect renal prognosis was 0.948, sensitivity was 85.7% and specificity was 90.9%. 72-hour after operation, the AUC of uL-FABP to detect renal prognosis was 0.935, sensitivity was 85.7% and specificity was 90.9%. Kaplan-Meier analysis revealed that uL-FABP before operation over 366.57 μg/g•Cr or uL-FABP 72-hour after operation over 223.60 μg/g•Cr were closely related to the poor progression of renal function. Conclusions uL-FABP and uL-NGAL have good accuracy in detecting AKI. The level of uL-FABP before operation and 72-hour after operation is helpful to predict the renal outcome of obstructive nephropathy.     

血清及尿NGAL和胱抑素C对新生儿缺血缺氧性肾损伤早期临床诊断的相关性分析

目的评估和比较血清及尿中性粒细胞胶原酶相关脂质运载蛋白(NGAL)和胱抑素C在新生儿缺氧缺血性肾功能损伤中的临床应用价值。方法采用酶联免疫吸附法(ELISA)和胶乳增强免疫比浊法对本院重度窒息70例缺血缺氧性肾功能损伤新生儿患者血、尿中NGAL和胱抑素C含量进行测定并与25例健康新生儿血、尿指标作对比。结果缺血缺氧性肾功能损伤新生儿患者血、尿胱抑素C显著高于健康新生儿,差异有统计学意义。血、尿胱抑素C预测AKI的曲线下面积AUC分别为0.83和0.87,检测阈值分别为1.和0.12 mg/L。然而,血清NGAL表现较差(AUC 0.44),但尿NGAL显示出对新生儿缺血缺氧性肾损伤诊断的显著区分(AUC 0.81),检测阈值为29.5 ng/mL,敏感度为88%,特异性为73%。结论血清和尿胱抑素C和尿NGAL在新生儿缺血缺氧性肾损伤的诊断中有重要意义,其指标的升高与肾脏损害程度密切相关。     

Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass

Abstract

Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and risk stratification, but have yet to find widespread clinical application. We measured urinary α and π glutathione S-transferases (α-GST and π-GST), urinary l-type fatty acid-binding protein (l-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before surgery, post-operatively and at 24?h after surgery in 93 high risk patient undergoing cardiopulmonary bypass (CPB) and assessed the ability of these biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5 post-operative days. Twenty-five patients developed AKI. π-GST (ROCAUC?=?0.75), lower urine Hepcidin:Creatine ratio at 24?h (0.77), greater urine NGAL:Cr ratio post-op (0.73) and greater serum CysC at 24?h (0.72) best predicted AKI. Linear combinations with significant improvement in AUC were: Hepcidin:Cr 24?h?+?post-operative π-GST (AUC?=?0.86, p?=?0.01), Hepcidin:Cr 24?h?+?NGAL:Cr post-op (0.84, p?=?0.03) and CysC 24?h?+?post-operative π-GST (0.83, p?=?0.03), notably these significant biomarkers combinations all involved a tubular injury and a glomerular filtration biomarker. Despite statistical significance in receiver–operator characteristic (ROC) analysis, when assessed by ability to define patients to two groups at high and low risk of AKI, combinations failed to significantly improve classification of risk compared to the best single biomarkers. In an alternative approach using Classification and Regression Tree (CART) analysis a model involving NGAL:Cr measurement post-op followed by Hepcidin:Cr at 24?h was developed which identified high, intermediate and low risk groups for AKI. Regression tree analysis has the potential produce models with greater clinical utility than single combined scores.     

Value of joint detection of multiple biomarkers on early diagnosis of acute kidney injury in critical patients

Objective To assess the value of joint detection of serum cysteine proteinase inhibitors C (sCys-C), urinary kidney injury molecule 1 (uKIM-1), urinary neutrophil gelatinase-associated lipocalin(uNGAL) and urinary interleukin 18 (uIL-18) for early diagnosis of acute kidney injury (AKI) in critically ill patients. Methods A total of 256 adult patients who stayed Intensive Care Unit for 24 hours in the Third People's Hospital of Liaocheng between Aug 2011 and Dec 2012 were enrolled. According to Kidney Injury Net(AKIN) work, the patients were divided into non-AKI group and AKI group (including state 1, 2 and 3). The concentrations of urine NGAL, KIM-1, IL-18 and serum sCys-C were measured. The diagnosis value of four biomarkers joint detection and single detection for AKI were analyzed with the receiver operating characteristic (ROC) curve and the area under curve (AUC). Results (1) The levels of uNGAL, uKIM-1, uIL-18 and sCys-C were higher in patients with AKI than the patients with no AKI (P﹤0.01). (2) The area under curves of uNGAL, uKIM-1, uIL-18, sCys-C and joint detection were 0.742, 0.871, 0.803, 0.703, 0.925 respectively. (3) The sensitivity and specificity of parallel tests and serial tests of four biomarkers were 97.9%, 62.8%, 64.3% and 96.2% respectively. There were significant differences of sensitivity or specificity between single test and joint tests. Conclusions The urine NGAL, KIM-1, IL-18 and serum Cys-C are sensitive indexes for the early diagnosis of acute kidney injury. Joint detection has high value for early diagnosis of AKI.     

尿NGAL、NAG及KIM-1联合检测在高龄老年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(uNGAL)、尿N-乙酰β-D氨基葡萄糖苷酶(uNAG)及尿肾损伤分子-1(uKIM-1)的联合检测老年急性肾损伤中的诊断价值。方法选择2016年6月至2018年6月在泰山疗养院住院的老年患者184例,根据急性肾损伤网络(AKIN)标准为诊断标准,诊断AKI组116例(1期55例、2期39例、3期24例),非AKI组68例,检测并比较各组尿NGAL、NAG、KIM-1水平,用受试者工作特征曲线(ROC)及曲线下面积(AUC)分析3项生物学标志物对AIK的诊断价值。结果①AKI组尿NGAL、NAG、KIM-1明显高于对照组(P<0.05),3期尿NGAL、NAG、KIM-1明显高于2期和1期,2期明显高于1期(P<0.05);②尿NGAL、NAG、KIM-1单独诊断AKI的AUC分别为0.734、0.804、0.705;③3项标志物联合诊断AKI的灵敏度、特异度分别为84.9%、90.7%,高于各单项诊断。结论尿NGAL、NAG、KIM-1是诊断AKI的较好指标,联合诊断对高龄老年急性肾损伤的早期诊断有着更重要的价值。     

肝移植术后急性肾损伤的发生情况及其与预后的关系

Objective To investigate the incidence of acute kidney injury ( AKI) post-orthotopic liver transplant ( OLT ) and its association with prognosis. Methods Data of 28 patients received single OLT in our hospital from 2004 to 2006 were retrospectively analyzed. The incidence of AKI was investigated by new acute kidney injury network (AKIN) criteria. The follow-up was over one year. The prognosis of AKI patients at day 28 and 1 year was evaluated by Kaplan-Meier survival analysis. The association between AKI and prognosis was examined. Results A total of 193 patients were enrolled. The average age was (48.07±10.02) years old. The ratio of male to female was 4:1. One hundred and sixteen (60.1%) patients of post-OLT AKI were found, whose AKI stage 1, 2 and 3 were 50.0%, 21.6% and 28.4% respectively. Ten (8.6%) patients required renal replacement therapy (RRT) after OLT. In AKI post-OLT patients, day 28 and 1 year mortality were significantly higher than those in non-AKI patients (15.5% vs 0, 25.9% vs 3.9%, respectively, both P<0.05). Kaplan-Meier survival analysis showed the 1-year survival rates of AKI stage 1, 2, 3 post-OLT and non-AKI were 84.0%, 81.0%, 42.4% and 90.9%, respectively. The 1-year survival rate of non-AKI was significantly higher than that of AKI stage 1, 2, 3. The 1-year survival rate of AKI stage 3 was significantly lower than that of stage 1 and 2. There was no significant difference between AKI stage 1 and 2. Scr at 1 year post-OLT was significantly higher than that of baseline [（88.35±37.15） vs (73.70±33.88) ?滋mol/L, P<0.05）. The change of Scr value at 1 year compared to baseline in AKI patients was similar to non-AKI patients. However such change in AKI stage 2 and 3 was higher than that in stage 1. Conclusions The incidence of AKI post-OLT is quite high and associated to the poor prognosis in short and long periods. Renal function may decrease gradually which is associated to the AKI stage post-OLTI.     

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。