尿肾损伤分子1和肝型脂肪酸结合蛋白水平对脓毒症急性肾损伤的预测价值

目的:探讨尿中肾损伤分子1(KIM-1)和肝型脂肪酸结合蛋白(L-FABP)水平对脓毒症急性肾损伤(AKI)的预测价值。方法:收集117例脓毒症患者的临床资料,按照是否发生AKI分为脓毒症非AKI组(76例)和脓毒症AKI组(41例)。采用ELISA法检测尿KIM-1及L-FABP水平,运用受试者工作特征(ROC)曲线及曲线下面积(AUC),评估尿KIM-1、L-FABP水平及单独或联合检测对脓毒症AKI的预测价值。结果:与脓毒症非AKI组比较,脓毒症AKI患者尿KIM-1水平在-24、0、24、48 h时间点显著升高(均P 0. 05)。脓毒症患者发生AKI前24 h,将其尿KIM-1、L-FABP水平单独或联合检测的ROC曲线进行分析,AUC分别为0. 792、0. 781和0. 818(均P 0. 05)。当取KIM-1截断值为21. 00 ng/L时,敏感性为0. 8780,特异性为0. 6447。当取L-FABP截断值为14. 00 ng/L时,敏感性为0. 7317,特异性为0. 7368。建立KIM-1联合L-FABP检测的预测模型,取截断值为0. 2239时,敏感性为0. 8780,特异性为0. 6711。结论:脓毒症发生AKI前24 h检测患者尿KIM-1及L-FABP水平,有助于预测脓毒症AKI的发生,联合检测价值较单独检测更大。     

尿血管紧张素原早期预测老年脓毒症合并急性肾损伤的临床意义

目的研究尿血管紧张素原早期预测老年脓毒症合并急性肾损伤(AKI)的临床意义。方法选取100例老年脓毒症患者作为研究对象,根据改善全球肾脏病预后组织(KDIGO)的AKI诊断标准将患者分为AKI组和非AKI组,AKI组53例,非AKI组47例,观察测定分析两组在血清肌酐、尿血管紧张素原、尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)等指标情况及与脓毒症AKI诊断相关性。比较两组治疗前后的各项生活指标评分。结果AKI组各项生物标志物含量均明显高于非AKI组,差异有统计学意义(P<0.05),尿血管紧张素原、血清肌酐、尿NGAL和降钙素原与AKI的发生呈正相关;两组血清肌酐、尿AGT、尿NGAL含量的基线值比较,差异无统计学意义(P均>0.05),非AKI组各指标各个时间段比较差异无统计学意义(P均>0.05),而AKI组各个时间段各指标比较差异有统计学意义(P均<0.05)。血清肌酐在24 h开始上升,尿血管紧张素原在1 h开始上升,尿NGAL在6 h开始上升,尿血管紧张素原的敏感性更高;由受试者工作特征(ROC)曲线分析可得,尿血管紧张素原和尿NGAL敏感性和特异性均优于血肌酐;观察组诊断正确率96.00%,对照组诊断正确率为74.00%,观察组明显高于对照组(χ~2=5.31,P<0.05)。结论尿血管紧张素原联合尿NAGL与脓毒症AKI的诊断相关性高,诊断正确率高,对早期预测脓毒症AKI有很大的测定价值。     

尿神经导向因子-1与肾损伤因子-1联合检测在成人急性肾损伤早期诊断中的价值

目的探讨尿神经导向因子(Netrin)-1及肾损伤因子(KIM)-1联合检测在成人急性肾损伤(AKI)早期诊断中的价值与意义。方法选择152例AKI患者对尿中Netrin-1、KIM-1进行定量分析,选取50例健康人群作为对照组,同时检测相应时间点血清肌酐(Scr)及估计肾小球滤过(e GFR)水平,以2012年AKI临床实践指南肾损伤标准评估尿Netrin-1、KIM-1的预测效应。结果尿KIM-1与Netrin-1呈正相关(r=0.634,P0.01),与Scr呈负相关(r=-0.434,P0.01)。尿KIM-1和尿Netrin-1在AKI的诊断中,曲线下面积分别为0.914,0.910,P0.01。尿KIM-1与Netrin-1联合ROC曲线示曲线下面积为0.970,P0.01。结论检测AKI患者尿中Netrin-1、KIM-1变化,可以预测肾损伤程度,有助于临床诊断及治疗。     

视黄醇结合蛋白在急性肾损伤早期诊断及分期中的意义

目的观察视黄醇结合蛋白（RBP）在急性肾损伤（AKI）患者尿液中的变化,以探讨其在AKI早期诊断及分期中的意义。方法选择AKI患者62例,按照AKI的分期标准分为Ⅰ、Ⅱ、Ⅲ期组,同期选择健康体检者（对照组）40例,分别测定各组血清肌酐（Scr）、RBP、肾损伤分子-1（KIM-1）、尿N-乙酰-β-氨基葡萄糖苷酶（NAG）水平。结果AKI各组Scr、RBP、KIM-1、NAG水平均较对照组显著升高（P均〈0．05）。AKIⅢ期组较Ⅰ期、Ⅱ期组Scr、RBP、KIM-1明显升高（P均〈0．05）;Ⅱ期组较Ⅰ期组Scr、RBP、KIM-1明显升高（P均〈0．05）。结论RBP可以作为AKI早期诊断及评价病情严重程度的指标。     

尿KIM-1对心脏术后急性肾损伤的早期诊断价值

目的：评估尿肾损伤分子1（KIM-1）在心脏术后急性肾损伤（AKI）早期诊断中的应用价值。方法通过计算机检索Medline、Cochrane图书馆、EMBASE、Web of Science Database、Elsevier Science Direct Database、 CNKI、VIP数据库、万方数据库,查阅KIM-1早期诊断心脏术后AKI的临床试验,采用诊断精确性研究的质量评估方法（QUADAS）评价文献质量,Stata12．0和Meta-Disc1．4软件进行数据分析。结果共纳入9篇符合标准的诊断性研究,QUADAS得分均﹥9分,Spearman异质性检验r＝0．622、 P＝0．074,发表偏倚Egger线性回归法定量分析P＝0．001;敏感性分析的合并敏感度为0．87（95％CI为0．81～0．92）、P＝0．5776、I2＝0,特异度为0．78（95％CI为0．74～0．81）、P＝0．000、I2＝87．1％,阳性似然比为4．07（95％CI为2．70～7．12）、P＝0．000、I2＝78．2％,阴性似然比为0．19（95％CI为0．13～0．28）、P＝0．7303、I2＝0．0％,诊断比值比为28．03（95％CI为15．95～49．27）、P＝0．8640、I2＝0,汇总受试者工作曲线下面积（AUC）为0．9155。结论尿KIM-1在心脏术后（6～12h）诊断AKI的准确性较高。     

脓毒症休克合并急性肾损伤早期诊断研究

目的 探讨脓毒症休克合并急性肾损伤( AKI)的早期诊断方法,评价中性粒细胞明胶酶相关脂质运载蛋白(NGAL),白介素18(IL-18)和肾损伤分子1(KIM-1)在脓毒症休克合并AKI早期诊断中的意义. 方法 建立盲肠结扎穿孔(CLP)联合静脉注射内毒素诱导脓毒症休克合并AKI动物模型.将实验用新西兰大白兔70只随机分为对照组(n=35)和造模组(n=35).2组分别于造模后0、3、6、9、12h留取血、尿及组织标本.检测各组兔肾功能指标血肌酐(SCr)和血尿素氮(BUN);取兔肾组织进行病理组织学观察;ELISA法检测各组兔血液NGAL和尿液IL18、KIM-1的含量.结果 与对照组比较,造模组各时间点病理组织学观察均出现不同程度病变.与对照组比较,造模组12h时间点SCr水平明显升高(P＜0.05);BUN各时间点比较无统计学差异(P＞0.05);3h时间点NGAL即明显升高(P＜0.05);KIM-1和IL-18于9h时间点开始明显升高(P均＜0.05). 结论 脓毒症休克合并AKI时肾脏功能受损严重;NGAL和KIM-1可用于脓毒症休克合并AKI的早期诊断和预测.     

冠脉介入术后尿KIM-1的变化及其早期预测CIN的意义

目的：前瞻性研究冠脉介入诊疗术后患者尿液中肾损伤分子-1（KIM-1）的变化,评价其早期预测对比剂肾病（CIN）的临床意义。方法：160例接受冠脉造影（CAG）及介入治疗（PCI）患者,以发生CIN的病例作为CIN组（14例）,从未发生CIN的病例中以2：1选择配对患者作为对照（非CIN组,28例）。比较两组患者术前及术后24h、48h、72h血清肌酐（SCr）、24h尿KIM-1水平。结果：（1）160例患者中14例发生CIN（8．8％）;（2）与术前及非CIN组术后24h比较,CIN组术后24h尿KIM-1水平显著升高[3．81（3．54,4．32）ng／ml比4．33（4．06,4．63）ng／ml比5．21（4．86,5．42）ng／ml,P〈0．05];而SCr水平则在术后48h和72h才显著升高（P均〈0．05）;（3）Pearson相关分析显示CIN组患者尿KIM-1与SCr呈正相关（r=0．758,P=0．002）;（4）ROC曲线示尿KIM-1曲线下面积为0．839,检测截断点为4．595ng／ml时的敏感度与特异度为85．7％和71．4％。结论：尿。肾损伤分子-1能较肌酐更早反映肾功能的变化,对早期预测对比剂肾病有一定价值。     

血清胱抑素C及中性粒细胞明胶酶相关脂质蛋白与法洛四联症患儿术后急性肾功能损伤的相关性分析

目的:探讨血清胱抑素C(CysC)、中性粒细胞明胶酶相关脂质蛋白(NGAL)与法洛四联症(TOF)患儿术后急性肾功能损伤(AKI)的相关性分析。方法:回顾性分析2016年1月至2019年12月间,收治的228例行TOF根治术的患儿临床资料,根据术后是否发生AKI分为AKI组(n=54)和无AKI组(n=174)。比较两组术前、术后2 h、术后6 h CysC、NGAL水平,比较两组手术时间、体外循环时间、术中尿量,分析CysC、NGAL相关性,采用Logistics回归分析影响TOF术后AKI发生的因素,绘制ROC曲线评估术后2hCysC、NGAL单独及联合诊断TOF术后AKI的效能。结果:两组年龄、性别、体质量、术前血肌酐对比,差异均无统计学意义(P0.05);AKI组术后血肌酐高于无AKI组(P0.05);②术前两组CysC、NGAL水平对比,差异均无统计学意义(P0.05),术后2 h、术后6 h,AKI组CysC、NGAL水平均高于无AKI组(P0.05);手术前后,AKI组CysC、NGAL呈持续上升趋势(P0.05),无AKI组CysC先上升后下降(P0.05),无AKI组NGAL呈持续下降趋势(P0.05),不同组时间与CysC、NGAL水平存在交互效应(P0.05);③AKI组与无AKI组手术时间、术中尿量对比,差异均无统计学意义(P0.05),AKI组体外循环时间高于无AKI组(P0.05);④Pearson相关分析法:CysC、NGAL呈正相关关系(P0.05);⑤术后2 h CysC、NGAL是影响TOF术后AKI发生的危险因素(P0.05);⑥ROC曲线显示:术后2 h CysC、NGAL诊断TOF术后AKI均差异有统计学意义(P0.05)。结论:血清CysC、NGAL与TOF术后AKI发生存在紧密联系,CysC联合NGAL诊断是评估早期AKI的高效能方案。     

不同时间血、尿肾损伤分子-1诊断冠心病介入术后急性肾损伤的临床意义

目的分析不同时间血、尿肾损伤分子-1(KIM-1)检测对冠心病行介入术后急性肾损伤早期诊断中的应用价值。方法选取我院心内科收治的诊断为冠心病并行介入术病人191例,根据急性肾损伤(AKI)诊断标准分为AKI组32例,非AKI组159例。收集所有病人术后0h、2h、4h、6h、8h、10h、12h、24h、48h、72h血液及尿液样本,检测各时间血清肌酐(SCr)和KIM-1,尿液KIM-1。结果 AKI组术后12h、24h、48h、72h血SCr值均明显高于0h基线值和非AKI组同时间Scr值(P0.05),且术后24h血SCr值较0h基线值升高超过50%,达到AKI诊断标准。AKI组术后血(4h、6h、8h、10h)、尿(6h、8h、10h、12h、24h)KIM-1水平均高于0h基线值和非AKI组(P0.05),6h(血)或8h(尿)时达到峰值。Pearson相关分析显示,AKI组术后血(4h、6h、8h、10h)、尿(6h、8h、10h、12h、24h)KIM-1水平均与术后24h血SCr呈正相关(P0.05);AKI组术后4h血KIM-1ROC曲线下面积为0.941,95%置信区间(95%CI)[0.907,0.975],以41.9ng/L为诊断界点时,敏感度为87.5%,特异度为88.7%;10h血KIM-1ROC曲线下面积为0.899,95%CI[0.846,0.953],以38.1ng/L为诊断界点时,敏感度为84.4%,特异度为81.8%;6h尿KIM-1ROC曲线下面积为0.858,95%CI[0.801,0.914],以314.9ng/L为诊断界值时,敏感度为84.4%,特异度为73.0%;24h尿KIM-1ROC曲线下面积为0.795,95%CI[0.727,0.863],以323.5ng/L为诊断界点时,敏感度为81.2%,特异度为71.1%。结论 4h~10h血KIM-1、6h~24h尿KIM-1水平升高对冠心病病人行介入术后AKI发生具有预测价值,可作为早期诊断AKI的一项重要参考指标。     

NGAL、NAG和炎症指标对脓毒症患者急性肾损伤早期诊断的价值

目的探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、N-乙酰-β-D氨基糖苷酶(NAG)和血降钙素原(PCT)、超敏C-反应蛋白(hs-CRP)、WBC对脓毒症患者急性肾损伤(AKI)早期诊断的价值。方法回顾性分析60例脓毒症患者的临床资料,按照患者入ICU 7 d内是否出现AKI分为AKI组和非AKI组,各30例。分析比较两组患者血NGAL、尿NGAL、尿NAG和各项炎症指标的不同。运用ROC曲线评价各指标对AKI早期诊断的敏感性和特异性。结果两组比较,尿NGAL(log10)、血PCT、血hs-CRP的差异有统计学意义(P均<0.001)。两组血NGAL(log10)、尿NAG差异无统计学意义(P均>0.05)。ROC曲线:尿NGAL的AUC为0.882(P<0.001),血PCT的AUC为0.756(P<0.001),血hs-CRP的AUC为0.739(P=0.001);当尿NGAL≥155.5 ng/mL时,诊断早期AKI的敏感性为0.833,特异性为0.900;当血PCT≥1.08 ng/mL时,诊断的敏感性为0.600,特异性为0.833;当血hs-CRP≥93.5 mg/L时,诊断的敏感性为0.567,特异性为0.867。结论脓毒症患者尿NGAL、血PCT和hs-CRP升高,对AKI的早期诊断有一定的临床价值。     

Novel Urinary Biomarkers in Detecting Acute Kidney Injury,Persistent Renal Impairment,and All-Cause Mortality Following Decongestive Therapy in Acute Decompensated Heart Failure

BackgroundNew urinary biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18), are proposed to allow a more reliable early diagnosis and prognosis of acute kidney injury (AKI) in acute decompensated heart failure (ADHF). Our aim was to compare the predictive value of urinary NGAL, KIM-1, and IL-18 for the occurrence of AKI, persistent renal impairment, and mortality in ADHF.Methods and ResultsEighty-three patients admitted for ADHF were analyzed. Urinary creatinine (Cr), NGAL, KIM-1, and IL-18 were measured at baseline. Serum Cr was measured daily during the next 4 days and again at outpatient follow-up after 6 months. Mortality data were prospectively collected. Urinary NGAL, KIM-1, and IL-18 were modestly correlated with each other (Spearman ρ ≤0.61) and poorly correlated with estimated glomerular filtration rate (eGFR; Spearman ρ ≤0.28). None predicted AKI, defined as a 25% decrease in eGFR, during the index hospitalization, but urinary IL-18/Cr was the strongest predictor of persistently elevated serum Cr ≥0.3 mg/dL after 6 months compared with baseline (area under the receiver operating characteristic curve 0.674; P = .013). Urinary IL-18 was also significantly associated with all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.16–1.87; P = .001).ConclusionsLike urinary NGAL, urinary KIM-1 and IL-18 are relatively modest predictors of AKI in ADHF. Among these novel renal biomarkers examined, further investigations regarding the prognostic value of urinary IL-18 are warranted.     

急性肾损伤早期生物学标志物研究

急性肾损伤是由于各种原因引起的肾脏功能在短时间内(几小时或几天)急剧下降而引起的一系列临床综合征。由于目前仍没有急性肾损伤早期敏感特异的指标为其诊治带来极大困难。该文通过对半胱氨酸蛋白酶抑制蛋白C、中性粒细胞凝胶酶相关脂质运载蛋白、肾损伤分子-1等急性肾损伤早期标志物的阐述,探讨其在急性肾损伤中的诊断价值,为急性肾损伤的早期诊断、肾功能评估分级及其早期治疗、预后提供科学依据。本文对近年来关于肾损伤早期标志物进行了一个综合的总结。     

Urinary Biomarkers in the Early Detection of Acute Kidney Injury after Cardiac Surgery

Background and objectives: Serum creatinine (Scr) does not allow for early diagnosis of acute kidney injury (AKI). The diagnostic utility of urinary kidney injury molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), and neutrophil gelatinase associated lipocalin (NGAL) was evaluated for the early detection of postoperative AKI in a prospective study of 90 adults undergoing cardiac surgery.Designs, setting, participants, & measurements: Urinary KIM-1, NAG, and NGAL were measured at 5 time points for the first 24 h after operation and normalized to the urinary creatinine concentration after cardiac surgery. Receiver-operating characteristic curves were generated and the areas under the curve (AUCs) compared for performance of biomarkers in detection of postoperative AKI.Results: Thirty-six patients developed AKI, defined as an increase in Scr of ≥0.3 mg/dl within 72 h after surgery. The AUCs for KIM-1 to predict AKI immediately and 3 h after operation were 0.68 and 0.65; 0.61 and 0.63 for NAG; and 0.59 and 0.65 for NGAL, respectively. Combining the three biomarkers enhanced the sensitivity of early detection of postoperative AKI compared with individual biomarkers: the AUCs for the three biomarkers combined were 0.75 and 0.78. The performance of combining biomarkers was even better among 16 early postoperative AKI patients with AUCs of 0.80 and 0.84, respectively.Conclusions: The results of this study support that a combination of urinary biomarkers may allow for early detection of postoperative AKI after cardiac surgery before a rise in Scr.Acute kidney injury (AKI) is an important cause of morbidity and mortality in hospitalized patients (1). The incidence of hospital-acquired AKI varies from 5% in patients with normal preoperative renal function to 25% in intensive care unit (ICU) patients (2–4). Mortality rates of patients with postoperative AKI range from 40 to 60% among ICU patients who require a renal replacement therapy (5–7). Dialysis remains the only U.S. Food and Drug Administration approved treatment option for established AKI.Recently, two new definitions of AKI have been developed: RIFLE (risk, injury, failure, loss, and ESRD) and AKIN (acute kidney injury network) criteria (8,9). It is, however, a challenge to detect AKI in a timely fashion with current RIFLE and AKIN criteria because these definitions are entirely based on increases of serum creatinine (Scr) or decreases of urine output. Scr is insensitive for the early detection of AKI because the change in Scr does not discriminate the time and type of renal insult or the site and extent of glomerular or tubular injury (8,10).Several proteins and biochemical markers emerged as sensitive and specific biomarkers capable of detecting acute tubular injury early and proved to be promising biomarkers as indicators of AKI in recent human studies (11,12). These include N-acetyl-β-D-glucosaminidase (NAG), neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, and IL-18 (13–25). However, there are no previously reported data for the temporal expression pattern of urinary KIM-1 and NAG before the development of AKI in adult patients. In addition, there is a large discrepancy in the performance of NGAL as an early AKI marker between adult and pediatric AKI patients (15,17,19,20). Furthermore, there are few data on the influence of prolonged duration of storage at −80°C and the number of freeze-thaw cycles on stability of urinary biomarkers at the present time, which will be critical to ongoing validation studies of potential tandem AKI biomarkers (26).In this study, we studied the diagnostic utility of urinary KIM-1, NAG, and NGAL as biomarkers separately and in combination for the early detection of postoperative AKI and the temporal expression patterns of urinary biomarkers before the development of postoperative AKI in patients undergoing cardiac surgery. In addition, the stability of urinary KIM-1, NAG, and NGAL were tested with various handling and storing conditions to evaluate the accuracy of the biomarker measurement because our prospective collected urine samples were frozen at −80°C for 1 yr and were subjected to at least two freeze-thaw cycles before measurement for KIM-1 and NAG.     

Time of injury affects urinary biomarker predictive values for acute kidney injury in critically ill,non-septic patients

Background

The predictive value of acute kidney injury (AKI) urinary biomarkers may depend on the time interval following tubular injury, thereby explaining in part the heterogeneous performance of these markers that has been reported in the literature. We studied the influence of timing on the predictive values of tubular proteins, measured before the rise of serum creatinine (SCr) in critically ill, non-septic patients.

Methods

Seven hundred adult critically ill patients were prospectively included for urine measurements at four time-points prior to the rise in serum creatinine (T?=?0, -16, -20 and -24 h). Patients with sepsis and or AKI at ICU entry were excluded. The urinary excretion of the proteins, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), which are up-regulated in the distal and proximal tubules, respectively, were measured as well as the constitutive cytoplasmatic enzymes, π- and α-glutathione-S-transferase (GST), which are released by the distal and proximal tubules, respectively.

Results

Five hundred and forty-three subjects were eligible for further analyses; however, 49 developed AKI in the first 48 h. Both NGAL (P?=?0.001 at T?=?-24 vs. non-AKI patients) and KIM-1 (P?<?0.0001 at T?=?0 vs. non-AKI patients) concentrations gradually increased until AKI diagnosis, whereas π- and α-GST peaked at T?=?-24 before AKI (P?=?0.006 and P?=?0.002, respectively vs. non-AKI patients) and showed a rapid decline afterwards. The predictive values at T?=?-24 prior to AKI were modest for π- and α-GST, whereas NGAL sufficiently predicted AKI at T?=?-24 and its predictive power improved as the time interval to AKI presentation decreased (area under the receiver operating characteristic curve; AUC?=?0.79, P?<?0.0001). KIM-1 was a good discriminator at T?=?0 only (AUC?=?0.73, P?<?0.0001).

Conclusions

NGAL, KIM-1, pi- and alpha-GST displayed unique and mutually incomparable time dependent characteristics during the development of non-sepsis related AKI. Therefore, the time-relationship between the biomarker measurements and the injurious event influences the individual test results.

     

尿L-FABP、KIM-1、NGAL和血清cystatin C在糖尿病肾病中的变化及意义

目的 探讨尿液肝型脂肪酸结合蛋白(L-FABP)、肾损伤分子-1(KIM-1)、中性粒细胞明胶酶相关载脂蛋白(NGAL)和血清半胱氨酸蛋白酶抑制剂(cystatin)C水平在糖尿病肾病患者中的改变以及临床意义.方法 纳入2011年10月至2012年10月泸州医学院附属医院内分泌科确诊为2型糖尿病(T2DM)的住院患者118例,根据尿微量白蛋白/肌酐比值(UACR)分为正常白蛋白尿组(n=45)、微量白蛋白尿组(n=42)以及大量白蛋白尿组(n=31).同时选择同期健康体检者41名作为正常对照组.采用ELISA法检测尿L-FABP、KIM-1和NGAL,免疫比浊法检测血清cystatin C.所有尿液检测指标经尿肌酐校正,比较各组间各标志物的变化情况及与UACR、估计的肾小球滤过率(eGFR)的相关性.结果 与正常对照组相比,糖尿病各组尿L-FABP和血清cystatin C水平明显升高,(x2=77.959,104.003,P均＜0.05);尿KIM-1水平亦明显升高(x2=29.711,P＜0.05).微量白蛋白尿组与大量白蛋白尿组尿NGAL水平较正常对照组和正常白蛋白尿组明显升高(x2=23.833,P＜0.05),但在正常白蛋白尿组与正常对照组间未见明显变化.尿L-FABP、KIM-1、NGAL及血清cystatin C与UACR呈正相关(r=0.719,0.427,0.327,0.726,P均＜0.01);仅L-FABP、血清cystatin C与eGFR呈负相关(r=-0.301、-0.791,P＜ 0.01).结论 尿L-FABP、KIM-1、NGAL和血清cystatin C在糖尿病肾病早期显著升高,其中尿L-FABP和血清cystatin C可能是反映糖尿病肾损伤较好的生物学指标.     

Acute kidney injury in acute-on-chronic liver failure is different from in decompensated cirrhosis

AIM To evaluate the differences in acute kidney injury(AKI) between acute-on-chronic liver failure(ACLF) and decompensated cirrhosis(DC) patients. METHODS During the period from December 2015 to July 2017, 280 patients with hepatitis B virus(HBV)-related ACLF(HBV-ACLF) and 132 patients with HBV-related DC(HBV-DC) who were admitted to our center were recruited consecutively into an observational study. Urine specimens were collected from all subjects and the levels of five urinary tubular injury biomarkers were detected,including neutrophil gelatinase-associated lipocalin(NGAL), interleukin-18(IL-18), liver-type fatty acid binding protein(L-FABP), cystatin C(CysC), and kidney injury molecule-1(KIM-1). Simultaneously, the patient demographics, occurrence and progression of AKI, and response to terlipressin therapy were recorded. All patients were followed up for 3 mo or until death after enrollment. RESULTS AKI occurred in 71 and 28 of HBV-ACLF and HBV-DC patients, respectively(25.4% vs 21.2%, P = 0.358). Among all patients, the levels of four urinary biomarkers(NGAL, CysC, L-FABP, IL-18) were significantly elevated in patients with HBV-ACLF and AKI(ACLF-AKI), compared with that in patients with HBV-DC and AKI(DC-AKI) or those without AKI. There was a higher proportion of patients with AKI progression in ACLF-AKI patients than in DC-AKI patients(49.3% vs 17.9%, P = 0.013). Fortythree patients with ACLF-AKI and 19 patients with DC-AKI were treated with terlipressin. The response rate of ACLFAKI patients was significantly lower than that of patients with DC-AKI(32.6% vs 57.9%, P = 0.018). Furthermore, patients with ACLF-AKI had the lowest 90 d survival rates among all groups(P 0.001).CONCLUSION AKI in ACLF patients is more likely associated with structural kidney injury, and is more progressive, with a poorer response to terlipressin treatment and a worse prognosis than that in DC patients.     

老年患者造影剂肾损害的诊断指标探讨

目的通过对比分析老年患者造影前后血清肌酐（SCr）及血清胱抑素C（CysC）等生物学指标的变化,探讨更适用于老年患者造影剂肾损害的诊断指标。方法收集2010年5月至2011年2月于北京友谊医院医保中心及心内科接受血管造影检查的年龄≥60岁患者的相关资料共41例。用酶法测定入选患者造影前及造影后2h,24h,48h,72hSCr值。留取患者造影前及造影后2h、24h、48h、72h血清及尿液样本,予酶联免疫吸附测定法检测患者血清CysC、中性粒细胞明胶酶相关性载脂蛋白（NGAL）及尿液NGAL、肾损伤分子1（KIM-1）数值,进行造影前后的对比分析。结果依照传统造影剂肾病（CIN）的诊断标准,入选患者中1例发生CIN,患病率为2．44％。依照急性肾损伤网络（AKIN）诊断标准,入选患者中3例发生急性肾损伤,患病率为7．32％。造影后CysC升高≥25％的患者有27例,所占比例为65．9％。CysC水平在造影后24h及48h较造影前水平显著升高,SCr水平在造影前后未见明显改变。造影后CysC升高≥25％患者的血清NGAL、尿NGAL及尿KIM-1造影后的上升幅度明显高于CysC升高〈25％的患者。结论以SCr为指标的传统CIN诊断标准不适合老年患者,CysC可能更加及时、准确地反映老年患者的造影剂肾损害。     

Clinical Significance of Urinary Biomarkers in Patients With Primary Focal Segmental Glomerulosclerosis

Background

Focal segmental glomerulosclerosis (FSGS) is often accompanied with tubulointerstitial lesion. This study aimed to assess the role of urinary biomarkers in predicting tubulointerstitial lesion and treatment response in FSGS patients.

Changes of the tubular markers in type 2 diabetes mellitus with glomerular hyperfiltration

Aim

To assess whether glomerular hyperfiltration (GHF) could result in renal tubular damage in type 2 diabetes mellitus (T2DM) patients.

Methods

Reference value of estimated glomerular filtration rate (eGFR) was determined in 248 healthy individuals based on serum CysC levels. GHF was defined as an eGFR exceeding the sex-specific 97.5th percentile in non-diabetic individuals. In the present study, 30 with GHF, 58 with norm-GFR T2DM, and 24 healthy controls were recruited. Tubular markers, such as urinary N-acetyl-β-d-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1), as well as serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), were measured and compared. The correlation of these markers with eGFR was analyzed in the GHF group.

Results

The GHF group had higher urinary NGAL and KIM-1 levels but lower serum NGAL level than the norm-GFR and control groups. Slightly decreased serum NGAL and increased urinary NGAL levels were also noted in the norm-GFR group compared with those of the controls. There was no statistical difference in the urinary NAG values among the three groups. Correlation analysis showed that eGFR was positively related to fasting blood glucose (FBG), HbA1c, urinary NGAL, and KIM-1, but negatively with serum NGAL in the GHF group.

Conclusion

Higher urinary tubular damage markers were found in T2DM patients with GHF than the norm-GFR and control groups, probably a direct proof that GHF is a deleterious factor for diabetic nephropathy.