尿中性粒细胞明胶酶相关脂质运载蛋白和白细胞介素-18对重症患者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脂质运载蛋白(uNGAL)和尿IL-18(uIL-18)对重症患者急性肾损伤(AKI)的早期诊断价值.方法 以我院ICU收治的92例危重症患者为观察对象,将1周内符合RIFLE诊断标准的AKI患者纳入AKI组(46例),对照组(46例)由匹配的非AKI患者构成.每日收集尿标本,持续1周.ELISA检测uNGAL和uIL-18水平.用受试者工作特征曲线(ROC)评价uNGAL、uIL-18和血肌酐(SCr)对AKI的诊断作用.结果 与AKI诊断前3天比较,AKI诊断前2天患者uNGAL明显增高(P<0.05),但uIL-18和SCr无明显改变(P值均>0.05);AKI诊断前1天AKI患者uNGAL和uIL-18明显增高(P值均<0.05),但SCr无明显改变(P>0.05);观察期间对照组uNGAL、uIL-18和SCr均无明显变化(P值均>0.05).AKI诊断前3天uNGAL、uIL-18和SCr对AKI均无诊断作用;AKI诊断前2天uNGAL的ROC曲线下面积为0.840(95%CI 0.672～1.009,P<0.05),对AKI具有诊断作用,而uIL-18和SCr均无诊断作用;AKI诊断前1天uNGAL和uIL-18的ROC曲线下面积分别为0.830(95%CI 0.711～0.950,P<0.05)和0.818(95%CI 0.697～0.938,P<0.05),对AKI具有诊断作用,而SCr无诊断作用.结论 uNGAL和uIL-18对重症患者AKI可能具有早期诊断价值.     

尿液肾损伤分子1:预测梗阻性肾病肾脏预后的生物学标志物

目的:探讨尿液肾损伤分子1(uKIM-1)、尿中性粒细胞明胶酶相关脂质运载蛋白分子(uNGAL)在梗阻性肾病所致急性肾损伤(AKI)诊断中的价值,评价其在预测肾脏预后中的价值.方法:收集30例梗阻性肾病患者解除梗阻前后不同时相的尿液标本,应用ELISA方法检测uKIM-1、uNGAL水平,进行分析、比较.随访1年,评估uKIM-1、uNGAL在梗阻性肾病肾脏预后判断中的应用价值.结果:发生AKI的患者uKIM-1和uNGAL水平显著升高,uKIM-1、uNGAL与血清肌酐成正相关,曲线下面积(AUC)分别为0.943和0.900.肾脏预后差的患者术后72h uKIM-I水平显著升高.ROC曲线分析uKIM-1在肾脏预后判断中的AUC为0.912,敏感度85.7％,特异度84.6％.Kaplan-Meier生存曲线分析示出现术后72h尿KIM-1＞ 156.00 pg/( mg·Cr),与不良预后呈明显相关性.结论:uKIM-l、uNGAL对诊断梗阻性肾病所致AKI有较高的准确性,术后72h uKIM-1有助梗阻性肾病肾脏预后的判断.     

特利加压素联合白蛋白输注治疗肝硬化并发Ⅱ型肝肾综合征患者临床疗效及尿NGAL和KIM-1水平的变化*

目的 观察应用特利加压素联合白蛋白输注治疗肝硬化并发Ⅱ型肝肾综合征患者的临床效果及血清血管紧张素Ⅱ(AngⅡ)、尿中性粒细胞明胶酶相关脂质运载蛋白(uNGAL)和尿肾损伤因子-1(uKIM-1)水平的变化。方法 2017年7月~2019年5月我院收治的60例肝硬化并发Ⅱ型肝肾综合征患者,采用随机数字表法分为对照组30例和观察组30例,分别给予静脉滴注白蛋白或在此基础上,应用特利加压素治疗,观察两周。采用化学发光法检测血清AngⅡ水平;采用ELISA法检测uKIM-1水平,采用胶体金法检测uNGAL水平。结果 在治疗两周末,观察组腹水消退和尿量增加等有效率为85.3%,显著大于对照组的63.3%(P<0.05);观察组24 h尿量为(1256.7±530.5)mL,显著大于对照组【(824.9±384.4)mL,P＜0.05】,体质量为(51.8±4.5)kg,显著低于对照组【(57.6±4.8)kg,P＜0.05】,腹围为(88.2±5.8)cm,显著小于对照组【(95.7±6.4)cm,P＜0.05】;观察组尿素氮(BUN)水平为(10.8±2.4)mmol/L,显著低于对照组【(14.7±3.2)mmol/L,P＜0.05】,sCr水平为(139.7±14.4)μmol/L,显著低于对照组【(154.9±17.5)μmol/L,P＜0.05】,血钠水平为(135.8±8.2)mmol/L,显著高于对照组【(132.2±7.9)mmol/L,P＜0.05】;观察组血清AngⅡ水平为(14.6±1.5)pg/mL,显著低于对照组【(18.3±1.8)pg/mL,P＜0.05】,uNGAL水平为(1.0±0.4)μg/L,显著低于对照组【(1.2±0.2)μg/L,P＜0.05】,uKIM-1水平为(3.8±0.4)μg/L,显著低于对照组【(4.4±0.3)μg/L,P＜0.05】。结论 应用特利加压素联合白蛋白输注治疗肝硬化并发Ⅱ型肝肾综合征患者能显著增加尿量,消退腹水,改善肾功能,可能与降低了血清AngⅡ水平,增加尿uNGAL和uKIM-1排泄有关,值得临床进一步观察。     

血、尿中性粒细胞明胶酶相关脂质运载蛋白与胱抑素C对肝硬化并发急性肾损伤的诊断价值

目的检测血、尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、胱抑素C(CysC)水平,分析其对肝硬化患者并发急性肾损伤(AKI)的早期诊断价值。方法选择2015年1月-2017年3月于武汉市汉南区红十字会医院就诊的肾功能正常的肝硬化患者236例,依据入院后48 h内是否并发AKI分为AKI组78例,非AKI组158例,选择同期健康体检者100例为对照组。采用ELISA法检测血清NGAL(sNGAL)和尿液NGAL(uNGAL)及血清CysC浓度,并将血肌酐(SCr)浓度和肾小球滤过率(GFR)进行组间比较。计量资料多组间比较采用单因素方差分析,进一步两组间比较采用SNK-q检验;相关分析采用Pearson相关分析法;利用受试者工作特征曲线(ROC曲线)分析相关指标的诊断价值。结果入院48 h,AKI组sNGAL、uNGAL、CysC同非AKI组和对照组相比,差异均有统计学意义(P值均0.05);将AKI组依照肾损伤标准进行分期,分期高的患者sNGAL、uNGAL浓度显著高于分期低的患者,差异均有统计学意义(P值均0.05);与入院前比较,入院6 h时sNGAL、uNGAL及CysC水平开始升高,而Scr与GFR入院48 h才开始变化,即sNGAL、uNGAL与CysC开始上升时间明显早于Scr与GFR(P值均0.05)。AKI组患者sNGAL、uNGAL及CysC浓度与SCr呈正相关(r值分别为0.650、0.681、0.581,P值均0.05)。ROC曲线示,sNGAL曲线下面积为0.845±0.435,最佳阈值为542.68μg/L,敏感度为0.824,特异度为0.794;uNGAL曲线下面积为0.836±0.326,最佳阈值为75.12μg/L,敏感度为0.816,特异度为0.766;CysC曲线下面积为0.818±0.267,最佳阈值为1.48 mg/L,敏感度为0.808,特异度为0.732。结论 NGAL与CysC可以作为肝硬化患者发生AKI的早期诊断指标,对了解肝硬化患者的肾功能损伤状况及制订相应措施具有重要意义。     

地震相关挤压综合征急性肾损伤患者尿中肾损伤标志物的变化及意义

目的:评估地震相关挤压综合征(crush syndrome,CS)急性肾损伤透析患者尿中中性粒细胞明胶酶脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)、IL-18及肾损伤分子(kidney injury molecule-1,KIM-1)的变化,以及这些指标与血肌酐、尿肌红蛋白等指标的关系,研究治疗前后肾损伤标志物的改变. 方法:研究纳入16例CS急性肾损伤透析患者,12名正常对照,对10例CS患者随访14d,用ELISA方法分别测定两组尿IL-18、NGAL及KIM-1;同时测定患者尿肌酐、血肌酐、血肌红蛋白等生化指标.使用ATN-ISI'评估CS患者病情严重程度及转归. 结果:与对照组比较,CS患者:血肌酐明显升高[(324.0±189.7)μmol/L vs (72.1±15.7)μmol/L,P<0.01]、尿肌红蛋白明显升高[(593.5±381.4)ng/ml vs (8.7±1.7)ng/ml,P<0.01].肾损伤标志物尿IL-18[(59.54±41.31)μg/g vs (22.62±17.40)μg/g,P<0.01]、尿NGAL[(1.06±1.07)μg/g vs (0.39±0.30)μg/g,P<0.05]、尿KIM-1[(1.87±1.47)μg/g vs (0.92±0.62)μg/g,P<0.05)均明显升高.Pearson分析提示尿KIM-1、尿NGAL、尿IL-18之间存在正相关,P值均小于0.05;NGAL与ATN-ISI呈正相关(r=0.65,P<0.01).病程前后(n=10)NGAL含量分别为(0.86±0.51)μg/g、(0.78±0.64)μg/g,P>0.05,IL-18含量分别为(57.33±36.97)μg/g、(97.14±118.72)μg/g,(P>0.05),KIM-1含量分别为(1.78±1.61)μg/g、(1.77±1.55)μg/g,(P>0.05).其中有3例患者脱离透析治疗,病程第14d其尿NGAL(1.14±0.54)μg/g,(0.37±0.23)μg/g、KIM-1(3.01±1.54)μg/g,(0.75±0.52)μg/g、IL-18(71.73±30.34)μg/g,(24.13±12.23)μg/g,均明显下降. 结论:CS接受透析的患者肾损伤标志物IL-18、NGAL、KIM-1均明显升高,其中NGAL与肾脏损伤程度正相关,上述指标可随CS患者肾功能的恢复而下降.     

特利加压素联合白蛋白输注治疗肝肾综合征患者疗效及尿NGAL和KIM-1对疗效的预测价值

目的 探讨尿中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）和肾损伤因子-1（uKIM-1）对特利加压素联合白蛋白输注治疗肝肾综合征患者疗效的预测价值。方法 2017年5月1日~2018年4月30日就诊于北京佑安医院的肝硬化并发I型HRS患者19例,应用特利加压素联合白蛋白输注治疗,采用ELLSA法测定尿NGAL和KIM-1水平。结果 经特利加压素联合白蛋白输注治疗4 d后,应答12例（63.2%）,未应答7例（36.8%）;两组患者年龄和性别比较,差异无统计学意义（P=0.605和P=0.386）,两组自发性细菌性腹膜炎（SBP）和上消化道出血发生率比较,差异无统计学意义（P=0.526和P=0.525）,两组血清ALT、AST、TBIL、DBIL、BUN、ALB和血小板计数、血红蛋白、白细胞计数等基线资料比较,差异无统计学意义（P>0.05）;应答组患者PTA显著高于非应答组（P=0.006）,血肌酐水平显著低于非应答组（P=0.043）;应答组患者uNGAL/Cr 为21.8（7.8~65.5） μg/g,uKIM-1/Cr水平4.9（2.0~7.7） μg/g,均显著低于非应答组【分别为97.8（27.1~358.2） μg/g（P=0.010）和9.1（5.5~13.6） μg/g,P=0.001】;早期应答组患者90 d生存率为75.0%,非应答组为42.9%,差异无统计学意义（P=0.182）;血肌酐与uNGAL/Cr呈正相关（r=0.549,P=0.022）,而与uKIM-1/Cr无显著相关（r=0.213,P=0.411）。结论 基线血肌酐、PTA和尿NGAL水平可以预测特利加压素联合白蛋白输注治疗的肝硬化并发HRS患者的疗效,值得进一步研究。     

急性肾损伤尿生物标志物研究进展

传统的血肌酐、尿素氮、尿量等指标不能反映急性肾损伤早期变化,近年来,随着检测技术的进步,多种能反映早期肾损伤的标志物被发现。该文对肾损伤分子1、中性粒细胞明胶酶相关脂质运载蛋白、白介素18、钠氢交换体亚型3、脂肪酸结合蛋白等尿生物标志物结构特征、代谢特点、临床意义进行综述。     

对比剂肾病早期肾损伤生物学标志物研究进展

对比剂肾病(CIN)指使用对比剂48~72 h内出现不能以其他原因解释的急性肾功能损害,目前尚缺乏诊断CIN的早期肾损伤生物学标志物。目前研究表明,通过监测血清胱抑素C、IL-18、中性粒细胞明胶酶脂质运载蛋白、尿液中肾损伤分子1(KIM-1)、L型脂肪酸结合蛋白等生物标志物可以早期发现对比剂对肾功能的损伤。     

肝硬化合并急性肾损伤的尿液相关预测因素分析

目的探讨肝硬化并发急性肾损伤(AKI)的预测因素。方法连续入组2017年5月-2018年4月于首都医科大学附属北京佑安医院就诊的肝硬化失代偿期患者105例,分为AKI组(49例)和非AKI组(56例)。收集患者临床一般资料以及实验室检查结果,留取患者入院时尿液标本,检测尿血管紧张素原(uAGT)、尿中性粒细胞明胶酶相关脂质运载蛋白(uNGAL)、尿肾损伤因子(KIM) 1,并以尿肌酐(UCr)校正。正态分布计量资料组间比较采用t检验,非正态分布计量资料组间比较采用Mann-Whitney U检验;计数资料组间比较采用χ2检验,进行logistic多因素分析,绘制受试者工作特征曲线(ROC曲线)评估预测效能。结果与非AKI组比较,AKI组患者合并上消化道出血及自发性腹膜炎的比例较高(χ2值分别为11. 420、8. 083,P值均0. 05),且白细胞计数、TBil、DBil、尿素氮、SCr均高于非AKI组(Z值分别为-3. 401、-2. 082、-2. 207、-5. 872、-7. 460,P值均0. 05),血Na低于非AKI组(t=-4. 905,P 0. 05); AKI组患者的uNGAL/UCr、uKIM-1/UCr高于非AKI组(Z值分别为-7. 654、-2. 395,P值均0. 05);多因素分析结果显示SCr、血Na、uNGAL/UCr均为肝硬化并发AKI的独立预测因素(P值均0. 05)。ROC曲线分析显示,SCr预测AKI的界值为88. 1μmol/L,其灵敏度93%、特异度82%,ROC曲线下面积(AUC)为0. 915[95%可信区间(95%CI):0. 850~0. 980]; uNGAL预测AKI的界值为1. 62μg/g,其灵敏度87%、特异度81%,AUC为0. 950 (95%CI:0. 911~0. 989); u NGAL联合SCr后预测AKI的AUC为0. 964 (95%CI:0. 931~0. 998)。结论 uNGAL是肝硬化合并AKI的独立危险因素,可用于肝硬化继发AKI的早期诊断,uAGT、uKIM-1不能独立预测肝硬化合并AKI的发生,其应用价值仍有待探索。     

尿神经突起导向因子1和结缔组织生长因子与妊娠期高血压疾病早期肾损伤的相关性

目的 探究尿神经突起导向因子1(Netrin-1)、结缔组织生长因子(CTGF)与妊娠期高血压疾病(HDCP)早期肾损伤的关系。方法 将上海儿童医学中心三亚市妇女儿童医院2020年2月到2022年2月收治的HDCP患者128例纳入研究,按照病情严重程度分作妊娠期高血压组(n=38)、子痫前期组(n=51)、重度子痫前期组(n=39),另选取同期正常妊娠孕妇43人作为对照组,检测并比较各组尿Netrin-1、CTGF水平,采用logistic回归分析HDCP患者早期肾损伤的影响因素。结果 各组研究对象的尿Netrin-1和CTGF水平对比,差异有统计学意义(F=191.210、1 714.664,P<0.05);且随着HDCP病情严重程度增加,尿Netrin-1水平逐渐降低,而CTGF水平逐渐升高(P<0.05);肾损伤组尿Netrin-1水平[(117.5±14.1)μg/L]低于无肾损伤组[(157.0±20.8)μg/L]和对照组[(215.2±27.8)μg/L],尿CTGF水平[(902.6±47.2)μg/L]高于无肾损伤组[(476.8±33.0)μg/L]和对...     

The efficacy of biomarkers in the diagnosis of acute kidney injury secondary to liver cirrhosis

This study is to investigate the role of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC) and creatinine in the diagnosis of acute kidney injury (AKI) secondary to liver cirrhosis.A total of 825 patients (including 540 liver cirrhosis patients and 285 healthy controls) were enrolled. Liver cirrhosis patients were further subdivided into AKI secondary to liver cirrhosis group (AKI group, 210 patients) and simple liver cirrhosis group (LC group, 330 patients). Serum NGAL/urine NGAL (sNGAL/uNGAL), and serum creatinine (sCr) levels as well as estimated glomerular filtration rates were measured. The diagnostic performances of these indicators in AKI secondary to liver cirrhosis were evaluated.The levels of sNGAL, uNGAL, CysC and sCr in the AKI group were significantly higher than those of LC and healthy control groups. However, the eGFR and c-aGFR of AKI group were significantly lower. With the progression of AKI (AKI-S1→AKI-S2→AKI-S3), the levels of sNGAL, uNGAL, CysC and sCr increased gradually, while the levels of c-aGFR and eGFR decreased gradually. The sNGAL, uNGAL and CysC were positively correlated with sCr (r = 0.638, 0.635, and 0.650), but negatively correlated with c-aGFR (r = -0.617, -0.606 and -0.655). However, eGFR had a negative correlation with sCr (r = -0.711), but a positive correlation with c-aGFR (r = 0.736). ROC curve analysis showed that the area under the curve for uNGAL was the largest (0.976), followed by sNGAL (0.967). The diagnostic efficacy of uNGAL and sNGAL in AKI group were 0.907 and 0.870, and the risk degrees were OR = 54.524 and 5.115, respectively.NGAL might perform better than sCr and CysC in the diagnosis of AKI secondary to liver cirrhosis, while uNGAL might be a better indicator than sNGAL in AKI diagnosis.     

“Normoalbuminuric” diabetic nephropathy: tubular damage and NGAL

The aim of this study was to demonstrate that neutrophil gelatinase-associated lipocalin (NGAL) increased before the onset of microalbuminuria in patients with type 1 diabetes mellitus (T1DM), representing an important biochemical parameter with high sensitivity and specificity to make a precocious diagnosis of “normoalbuminuric” diabetic nephropathy (DN). Serum NGAL (sNGAL) and urinary NGAL (uNGAL) levels were evaluated in a cohort of fifty patients affected by T1DM. They had no signs of clinical nephropathy. Thirty-five healthy subjects (HS) were recruited. sNGAL levels were significantly higher compared with those measured in HS [193.7 (103.2–405.4) vs. 46.4 (39.8–56.2) ng/ml; p < 0.0001], as were uNGAL levels [25.5 (14.2–40.2) vs. 6.5 (2.9–8.5) ng/ml; p < 0.0001]. sNGAL was found to be directly correlated with glycated hemoglobin. uNGAL also positively correlated with albuminuria, whereas an inverse correlation was found with uric acid. After multivariate analysis, significance was maintained for the correlation between uNGAL and microalbuminuria. In ROC analysis, sNGAL showed a good diagnostic profile such as uNGAL. NGAL increases in patients with T1DM, even before diagnosis of microalbuminuria representing an early biomarker of “normoalbuminuric” DN with a good sensitivity and specificity. NGAL measurement could be useful for the evaluation of early renal involvement in the course of diabetes.     

脓毒症急性肾损伤危险因素及对预后影响318例分析

目的分析脓毒症急性肾损伤的发生及对预后的影响。方法回顾性分析2008-01-01—2010-06-30收入中国医科大学附属一院重症加强病房(ICU)治疗的318例脓毒症患者临床资料,分为急性肾损伤组和非急性肾损伤组,应用Logistic回归对发病和死亡的相关因素进行统计学分析。结果 318例脓毒症患者中有119例发生急性肾损伤,发生率为37.4%,平均入ICU 2.4 d(0～26 d)开始出现急性肾损伤,持续时间7.8 d(1～63 d)。依发病24 h内最差指标分期:1期(危险期)74例(62.2%),2期(损伤期)18例(15.1%),3期(衰竭期)27例(22.7%)。60例患者接受持续性肾脏替代治疗(CRRT)治疗,平均CRRT时间为131.8 h(1～1008 h)。脓毒症急性肾损伤患者死亡48例(其中19例放弃治疗),占脓毒症患者的15.1%。有37例(31.1%)肾功能完全恢复,32例(26.9%)肾功能部分恢复,50例(42.0%)肾功能未恢复(其中23例拒绝CRRT治疗)。弥散性血管内凝血(DIC)、CPR术后及高SOFA评分是急性肾损伤的危险因素。高乳酸血症是脓毒症急性肾损伤患者死亡的危险因素。结论 ICU中脓毒症急性肾损伤的发生率及病死率高,DIC、CPR术后及高SOFA评分会增加脓毒症患者发生急性肾损伤的风险。高乳酸血症会增加脓毒症急性肾损伤患者的死亡风险。     

Elevated Urinary IL-18 Levels at the Time of ICU Admission Predict Adverse Clinical Outcomes

Background and objectives: Urine IL-18 (uIL-18) has demonstrated moderate capacity to predict acute kidney injury (AKI) and adverse outcomes in defined settings. Its ability to predict AKI and provide prognostic information in broadly selected, critically ill adults remains unknown.Design, setting, participants, & measurements: The study prospectively evaluated the capacity of uIL-18 measured within 24 hours of intensive care unit (ICU) admission to predict AKI, death, and receipt of acute dialysis in a large mixed-adult ICU population.Results: Of 451 patients, 86 developed AKI within 48 hours of enrollment and had higher median uIL-18 levels [426 (interquartile range [IQR]: 152 to 1183) pg/mg creatinine] compared with those without AKI [248 (IQR: 120 to 559) pg/mg]. The area under the receiver operating characteristic curve for uIL-18 predicting subsequent AKI within 24 hours was 0.62 (95% CI: 0.54 to 0.69) and improved modestly to 0.67 (95% CI: 0.53 to 0.81) in patients whose enrollment eGFR was ≥75 ml/min per 1.73 m². The highest median uIL-18 levels were observed in patients with sepsis at enrollment [508 (IQR: 230 to 1281) pg/mg], those receiving acute dialysis [571 (IQR: 161 to 1614) pg/mg] or dying [532 (IQR: 210 to 1614) pg/mg] within 28 days of ascertainment. After adjustment for a priori selected clinical predictors, uIL-18 remained independently predictive of composite outcome of death or acute dialysis within 28 days of ascertainment (odds ratio, 1.86 [95% CI: 1.31 to 2.64]).Conclusions: uIL-18 did not reliably predict AKI development, but did predict poor clinical outcomes in a broadly selected, critically ill adult population.The successful translation of promising preclinical treatments for acute kidney injury (AKI) has been hindered by a lack of early, accurate, and reliable indicators of injury. Furthermore, the discovery and validation of biologic markers able to differentiate between patients with mild or reversible forms of AKI and those that will progress to dialysis or not survive may also assist in risk-stratification for clinical trials. Recent efforts to identify biologic markers with early diagnostic and prognostic potential have yielded several candidates (1), including neutrophil gelatinase-associated lipocalin (NGAL) (2), liver fatty acid binding protein (L-FABP) (3), kidney injury molecule 1 (KIM-1) (4), cystatin C (5), and IL-18 (urine IL-18 [uIL-18]) (6,7).IL-18, a proinflammatory cytokine of the IL-1 superfamily, is found in monocytes, fibroblasts, and proximal renal tubular epithelial cells (8). The ability of IL-18 to mediate ischemic proximal tubular injury in mice and proinflammatory responses via its actions on the Toll-like receptor 4 has provided a rationale for its use as a human AKI biomarker (9,10). Previous studies have explored the ability of uIL-18 levels to predict AKI among children undergoing cardiopulmonary bypass (11), adults receiving a kidney transplant (12), and in children requiring mechanical ventilation (13). More recently, early translational studies in humans with limited sample sizes have demonstrated that uIL-18 levels can provide important prognostic information for AKI patients after cardiac surgery (11), 3-month graft function in kidney transplant patients (11), and survival in acute respiratory distress syndrome (ARDS) and in critically ill children (6,13).Using a large cohort of critically ill adults participating in the National Institutes of Health (NIH)-sponsored Validation of Biomarkers for Acute Lung Injury Diagnosis (VALID) study; we examined the ability of uIL-18 to predict both the development of AKI and clinically relevant outcomes including mortality and dialysis in a heterogeneous intensive care unit (ICU) population. Results were also compared independently and in combination with the previously reported performance of urine NGAL (uNGAL) (14).     

Neutrophil Gelatinase-Associated Lipocalin as an Early Sign of Diabetic Kidney Injury in Children

Objective:

There is some evidence indicating that histopathological changes in type 1 diabetes mellitus (T1DM) emerge before onset of microalbuminuria. The aim of our study was to determine whether urine neutrophil gelatinase-associated lipocalin (NGAL) levels can be considered as an early sign of diabetic kidney injury.

Methods:

Urine NGAL (uNGAL) levels and urinary NGAL/creatinine ratio (uNGAL/Cr) were assessed in 76 patients with T1DM and compared with the findings of 35 healthy individuals. The relationship of uNGAL levels with diabetes duration, body mass index (BMI), serum lipids, HbA1c, and microalbuminuria was also evaluated.

Results:

Mean uNGAL (100.16±108.28 ng/mL) and uNGAL/Cr (118.93-117.97 ng/mg) levels in both microalbuminuric and non-microalbuminuric diabetic patients were found to be higher than those in the control group (uNGAL: 21.46±18.59 ng/mL and uNGAL/Cr: 32.1±51.48 ng/mg) (p=0.0001).

Conclusion:

Urine NGAL level increases in the very early phase of T1DM before microalbuminuria develops. The patients with T1DM should be considered to have diabetic kidney injury from the time of diagnosis on and preventive interventions need to be initiated at an early stage to preclude the progression to end-stage renal disease.     

Urinary Biomarkers and Renal Recovery in Critically Ill Patients with Renal Support

Summary

Background and objectives

Despite significant advances in the epidemiology of acute kidney injury (AKI), prognostication remains a major clinical challenge. Unfortunately, no reliable method to predict renal recovery exists. The discovery of biomarkers to aid in clinical risk prediction for recovery after AKI would represent a significant advance over current practice.

Design, setting, participants, & measurements

We conducted the Biological Markers of Recovery for the Kidney study as an ancillary to the Acute Renal Failure Trial Network study. Urine samples were collected on days 1, 7, and 14 from 76 patients who developed AKI and received renal replacement therapy (RRT) in the intensive care unit. We explored whether levels of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary hepatocyte growth factor (uHGF), urinary cystatin C (uCystatin C), IL-18, neutrophil gelatinase-associated lipocalin/matrix metalloproteinase-9, and urine creatinine could predict subsequent renal recovery.

Results

We defined renal recovery as alive and free of dialysis at 60 days from the start of RRT. Patients who recovered had higher uCystatin C on day 1 (7.27 versus 6.60 ng/mg·creatinine) and lower uHGF on days 7 and 14 (2.97 versus 3.48 ng/mg·creatinine; 2.24 versus 3.40 ng/mg·creatinine). For predicting recovery, decreasing uNGAL and uHGF in the first 14 days was associated with greater odds of renal recovery. The most predictive model combined relative changes in biomarkers with clinical variables and resulted in an area under the receiver-operator characteristic curve of 0.94.

Conclusions

We showed that a panel of urine biomarkers can augment clinical risk prediction for recovery after AKI.     

中性粒细胞明胶酶相关载脂蛋白对糖尿病肾病早期诊断的意义

目的探讨糖尿病肾病（DN）患者血清和尿液中性粒细胞明胶酶相关载脂蛋白（NGAL）的改变及其临床意义。方法选择2型糖尿病（T2DM）患者57例,其中正常白蛋白尿组（NUAlb）16例、微量白蛋白尿组（MUAlb）19例、大量白蛋白尿组（CUAlb）22例;对照组（Con）17例。应用ELISA法检测血清和尿液中NGAL的浓度,并分析血清和尿液中NGAL的水平与肾小球滤过率（GFR）之间的相关关系。另检测尿素氮（BUN）、血肌酐（Scr）、尿白蛋白排泄率（UAER）等指标。结果（1）糖尿病患者血清NGAL（SNGAL）和尿液NGAL（uNGAL）浓度均较对照组显著升高（P均〈0．01）,其中CUAlb组患者的sNGAL及uNGAL浓度达到最高,与肾损害的严重程度相一致。（2）Pearson相关分析：糖尿病患者sNGAI。和uNGAL的水平均与GFR存在负相关（相关系数分别为r=0．862,P〈0．01;r=0．802,P〈0．01）。结论NGAL可能在DN的病理生理学方面起重要作用,检测血清和尿液NGAL浓度可能成为DN患者无创并有效的检测手段。